Clinical trial for the treatment of COVID-19 and COVID-like illness in primary care
| ISRCTN | ISRCTN55471843 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN55471843 |
| EudraCT/CTIS number | 2022-501707-27-01 |
| IRAS number | 1008573 |
| Secondary identifying numbers | EU-EcraidPC-1, IRAS 1008573 |
- Submission date
- 03/11/2022
- Registration date
- 21/11/2022
- Last edited
- 04/11/2024
- Recruitment status
- Recruiting
- Overall study status
- Ongoing
- Condition category
- Infections and Infestations
Prospectively registered
Protocol
Statistical analysis plan
Results
Individual participant data
Record updated in last year
Plain English summary of protocol
Background and study aims
Most people with COVID-19 and COVID-like illness do not become seriously ill. Some people, however, do go on to have more serious symptoms and may even need to be admitted to hospital. The aim of this study is to investigate the effectiveness and safety of medicinal products to treat COVID-19 and COVID-like illness in adult patients across Europe. This study will investigate whether the medicinal products help patients to recover patients faster, reduce the severity of the symptoms, reduce complications that require treatment in hospital, and prevent spread to family members/housemates.
Who can participate?
Patients aged 18 years or over and experiencing symptoms of a COVID-19 or COVID-like illness, presenting to primary care with COVID-19 and COVID-like-illness in Belgium, France, Germany, Ireland, Poland, Spain and the UK
What does the study involve?
Participants will be randomly allocated to receive either usual care alone or an investigational product, a placebo or a comparator product in addition to usual care.
Participants allocated to the usual care group will receive usual clinical care. Participants allocated to usual care + nitric oxide nasal spray will receive nitric oxide nasal spray (NONS) administered intranasally (into the nose) in addition to usual care, six times per day [two sprays per nostril, equivalent to 0.45 ml volume total per dose (four sprays)], for 7 days.
Participants allocated to usual care + saline nasal spray will receive a saltwater solution administered intranasally in addition to usual care, six times per day [two sprays per nostril, equivalent to 0.45 ml volume total per dose (four sprays)], for 7 days. The duration of the study for each participant is 6 months. Participants will be monitored daily for their acute symptoms for 28 days with a diary. They will receive a phone call between 28 days and 35 days in case data capture is not complete. Longer-term follow-up will be at 3 and 6 months by phone calls or electronic questionnaire. A combined throat/nose swab will be taken at the start of the study and on days 4, 7 and 14.
What are the possible benefits and risks of participating?
The overall benefits for participants in the intervention group are related to the prevention or treatment effects of the study drug on their COVID-19 or COVID-like illness. Taking part in the study can have possible disadvantages. Participants may experience side effects from the medicinal product. There may be a brief period of discomfort from (self-)taking the combined throat/nose swabs. Taking part in the study will take up some of the time of the participant.
Where is the study run from?
This study is being led by the University Medical Center Utrecht (UMCU) and managed by Ecraid (European Clinical Research Alliance on Infectious Diseases) in the Netherlands. It is a collaboration between the UMCU, the University of Oxford (UK), the University of Antwerp (Belgium), ECRIN (European Clinical Research Infrastructure Network, France) and Ecraid.
When is the study starting and how long is it expected to run for?
December 2021 to December 2025
Who is funding the study?
European Union
Who is the main contact?
1. Dr Alike van der Velden, a.w.vandervelden@umcutrecht.nl
2. Ilse Rietveld, Ilse.rietveld@ecraid.eu
Contact information
Dr Alike van der Velden
Principal Investigator
Principal Investigator
Universiteitsweg 100
Utrecht
3584 CG
Netherlands
| Phone | +31 (0)631118081 |
|---|---|
| a.w.vandervelden@umcutrecht.nl |
Ms Ilse Rietveld
Public
Public
Heidelberglaan 100
Utrecht
3584 CX
Netherlands
| Phone | +31 (0)631118658 |
|---|---|
| Ilse.rietveld@ecraid.eu |
Ms Jeri Nijland
Scientific
Scientific
Provinciehuis
Archimedeslaan 6
Utrecht
3584 BA
Netherlands
| Phone | +31 (0)6 3111787 |
|---|---|
| jeri.nijland@ecraid.eu |
Ms Chanelle Wigger
Scientific
Scientific
Provinciehuis
Archimedeslaan 6
Utrecht
3584 BA
Netherlands
| Phone | +31 6 5017 7196 |
|---|---|
| chanelle.wigger@ecraid.eu |
Study information
| Study design | Adaptive platform randomized double-blind multicentre trial |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | GP practice |
| Study type | Treatment |
| Participant information sheet | Not available in web format, please use contact details to request a participant information sheet |
| Scientific title | European Clinical Research Alliance on Infectious Diseases – PRIMary care adaptive platform trial for pandemics and Epidemics |
| Study acronym | ECRAID-Prime |
| Study objectives | Current study hypothesis as of 23/07/2024: The primary objective(s) of this platform study will be phase-dependent. To assess the efficacy of the study IP versus control on: 1. Time to first self-report of feeling recovered from symptoms of COVID-19 or COVID-like illness (for Phase IIb/III type evaluation, as specified in the relevant intervention-specific appendix). 2. Viral clearance and potential impact on biomarkers, for example on illness severity or immunological response (for Phase IIa type evaluation as specified in the relevant intervention-specific appendix). Previous study hypothesis: To test the safety and efficacy of treatments for patients presenting to primary care with COVID-19 and COVID-like-illness in a Phase II/III type evaluation, with the aim of determining whether treatments should progress to the next phase of evaluation, and evaluate the trial process and procedures to in order to optimize it and enhance recruitment. |
| Ethics approval(s) | Approved 25/05/2024, Federal Agency for Medicines and Health Products (avenue Galilee 5/03, Brussels, 1210, Belgium; +32 (0)25284000; ct.rd@fagg-afmps.be), ref: 2022-501707-27-01 |
| Health condition(s) or problem(s) studied | Reducing illness duration, complications, and possibly transmission of COVID-19 (SARS-CoV-2 infection) and other respiratory pathogens |
| Intervention | Eligible participants will be randomly allocated to receive either an investigational product (IP) or the specified control. Each investigational product has a matching placebo or comparator. Besides this matching placebo or comparator IP, usual care alone can be an additional control arm, this comparison is not double-blind. Participants will be randomised to receive either usual care alone or an investigational product, a placebo or a comparator product in addition to usual care. The ECRAID-Prime trial is a platform trial which means that multiple investigational products for the same illness can be tested simultaneously, and new interventions can be added during the course of the trial in accordance with pre-specified criteria. The names of all treatments of actions, including the control and details of the interventions (dose, duration, how it is administered) are intervention specific and will be described in intervention-specific appendices that will be added to the master protocol. Up to this point two investigational products have been selected. Participants will be randomized to receive either usual care alone or an investigational product, a placebo or a comparator product in addition to usual care. Potential participants can be included if they are eligible to be randomized to at least one investigational product, as well as the usual care arm. A. Usual care arm Participants randomized to the usual care arm will receive usual clinical care according to standard care in the specific country, at the discretion of responsible treating clinicians and according to the participant’s own decisions about self-care for the specific respiratory tract infection. B. Usual care + nitric oxide nasal spray Nitric oxide nasal spray (NONS) is a nitric oxide donor. NONS will be administered intranasally in addition to usual care, six times per day [two sprays per nostril, equivalent to 0.45 ml volume total per dose (four sprays)], for 7 days. C. Usual care + saline nasal spray Saline is a saltwater solution and will be administered intranasally in addition to usual care, six times per day [two sprays per nostril, equivalent to 0.45 ml volume total per dose (four sprays)], for 7 days. |
| Intervention type | Other |
| Primary outcome measure | Current primary outcome measure as of 23/07/2024: The primary outcome will be Phase dependent. For Phase IIb/III type evaluations the primary outcome will be: 1. Time to first self-report of feeling fully recovered from symptoms related to COVID-19 or COVID-like illness (days), measured using self-report for 28 days (or months 3 and 6 if not recovered). For Phase IIa type evaluations the primary outcome parameter will be: 2. Viral clearance assessed using semi-quantitive PCR at baseline and on days 4, 7 and 14, and impact on biomarkers of illness severity (if this will be an outcome parameter, then this will be specified in the intervention-specific appendix). The impact on biomarkers, for example on illness severity or immunological response is dependent on the specific investigational product (also the method and timepoints are dependent on the investigational product). If this will be an outcome parameter, then this will be specified in the intervention-specific appendix of that investigational product. So far, there are no compounds selected for which this will be an outcome parameter. Previous primary outcome measure from 03/02/2023 to 23/07/2024: Primary study endpoints are dependent on the study phase and can be: 1. Time to first self-report of feeling fully recovered from symptoms related to COVID-19 or COVID-like illness (days), measured using self-report for 28 days (or months 3 and 6 if not recovered). 2. Viral clearance assessed using semi-quantitive PCR at baseline and on days 4, 7 and 14, and impact on biomarkers of illness severity (if this will be an outcome parameter, then this will be specified in the intervention-specific appendix). The impact on biomarkers, for example on illness severity or immunological response is dependent on the specific investigational product (also the method and timepoints are dependent on the investigational product). If this will be an outcome parameter, then this will be specified in the intervention-specific appendix of that investigational product. So far, there are no compounds selected for which this will be an outcome parameter. Previous primary outcome measure as of 04/01/2023 to 03/02/2023: Primary study endpoints are dependent on the study phase and can be: 1. Time to first self-report of feeling recovered from symptoms related to COVID-19 or COVID-like illness (days), measured using self-report until the end of the study. 2. Viral clearance assessed using semi-quantitive PCR at baseline and on days 4, 7 and 14, and impact on biomarkers of illness severity (if this will be an outcome parameter, then this will be specified in the intervention-specific appendix). The impact on biomarkers, for example on illness severity or immunological response is dependent on the specific investigational product (also the method and timepoints are dependent on the investigational product). If this will be an outcome parameter, then this will be specified in the intervention-specific appendix of that investigational product. So far, there are no compounds selected for which this will be an outcome parameter. Previous primary outcome measure: Primary study endpoints are dependent on the study phase and can be: 1. Time to first self-report of feeling fully recovered from symptoms related to COVID-19 or COVID-like illness (days), measured using self-report until the end of the study 2. Viral clearance assessed using semi-quantitive PCR at baseline and on days 4, 7 and 14, and impact on biomarkers of illness severity (if this will be an outcome parameter, then this will be specified in the intervention-specific appendix). The impact on biomarkers, for example on illness severity or immunological response is dependent on the specific investigational product (also the method and timepoints are dependent on the investigational product). If this will be an outcome parameter, then this will be specified in the intervention-specific appendix of that investigational product. So far, there are no compounds selected for which this will be an outcome parameter. |
| Secondary outcome measures | Current secondary outcome measures as of 23/07/2024: 1. Sustained recovery, measured using self-report for 28 days 2. Time to first self-report of feeling fully recovered from individual symptoms of COVID-19 or COVID-like illness (days) (for Phase IIa type evaluation), measured using self-report for 28 days (or months 3 and 6 if not recovered). 3. Viral clearance (for Phase IIb and III type evaluation) assessed using semi-quantitive PCR at baseline and on days 4, 7 and 14, and impact on biomarkers of illness severity (if this will be an outcome parameter, then this will be specified in the intervention-specific appendix). The impact on biomarkers, for example on illness severity or immunological response is dependent on the specific investigational product (also the method and timepoints are dependent on the investigational product). If this will be an outcome parameter, then this will be specified in the intervention-specific appendix of that investigational product. So far, there are no compounds selected for which this will be an outcome parameter. 4. Time to first self-report of return to usual daily activity (days), measured using self-report until the end of the study 5. Presence, duration and severity of individual respiratory symptoms (runny/congested nose, sore throat, cough, fever shortness of breath, fatigue/tiredness, sweats/chills, headache, muscle, joint and/or body aches, loss of taste/smell, diarrhoea, other) as: absent, mild, moderate, severe, measured using a daily diary at day 0-28. 6. Participant-reported overall wellbeing, reported by rating of how well participant feels (scale 0-10) at day 0-28, and after 3 months and 6 months 7. Evaluation of overall safety of the IP by monitoring of AEs for the duration of IP administration and a defined period after the IP administration finishes. The duration of investigational product administration is dependent on the investigational product and will be specified in the intervention-specific appendix, for the selected IPs only side effects will be measured, as safety data are already available. 8. The use of additional antiviral medication (yes/no, name of medication), using a daily diary on days 0-28 9. The use of other prescribed and/or OTC medication for the respiratory tract infection, yes/no, using a daily diary at days 0-28 10. Occurrence of complications (i.e. hospitalisation, death; all-cause, non-elective hospitalisation) measured using weekly diary on days 7, 14, 21 and 28 or Serious Adverse Event reporting during the entire duration of study participation. 11. Impact on usual daily activities (work/education, caring for (grand-) children, household activities, sports, social life), as: no, slight, moderate, severe, not applicable, measured at day 1- 28, after 3 and 6 months 12. Healthcare utilisation for COVID-19 or COVID-like-illness (GP and hospital visits) measured using participant diary on days 1-28, months 3 and 6 13. Long-term consequences of COVID-19 or COVID-like-illness (e.g. cough, shortness of breath and/or difficulty breathing, fast heart rate, fatigue, tiredness and/or loss of energy, sleep alterations, loss of smell and/or taste, emotional sensitivity, depression and/or anxiety, concentration problems and/or difficulty thinking, muscle aches and or generalised body pains, diarrhoea and/or stomach pain, other) measured using a follow-up call or electronic questionnaire after 3 and 6 months 14. The incidence of COVID-19 and COVID-like-illness in other members of the household, measured using participants' diaries and/or swabbing the symptomatic household member(s) at daily day 0 - 28, if this will be measured using swabs in household members then timepoint(s) will be specified in the intervention specific appendix Exploratory parameters: 1. Emergence of mutations in causative pathogens in index cases and potentially in household members measured using combined pharyngeal/nasal swabs for participants swabs that are taken at Day 0, 4, 7 and 14 can be used, if this will be measured in household members then timepoint(s) will be specified in the intervention specific appendix 2. Experiences of researchers and network coordinators of setting up the trial in multiple countries, including views on optimising trial delivery, recruitment, and implementation (qualitative study) measured using interviews either remotely (by telephone or online or in person as appropriate). Interviews with researchers and network coordinators will take place throughout the period of ECRAID-Prime prior to trial set-up through to the completion of recruitment and follow-up of patients. We will aim to include longitudinal interviews, interviewing the same participant at multiple timepoints, where possible, to gain insights into how researchers apply learning to improve trial processes throughout the study 3. Healthcare professionals’ views and experience of taking part in the trial (in the context of a pandemic), the novel trial design, recruiting patients and views on the intervention(s) (qualitative study) measured using interviews either remotely (by telephone or online or in person as appropriate). Interviews with healthcare professionals will take place throughout the trial and will focus on key timepoints such as the start of recruitment and the introduction of a new intervention arm. 4. Patient views and experiences of taking part in the trial and trial interventions, including how they conceptualise their illness and recovery (qualitative study) measured using interviews either remotely (by telephone or online or in person as appropriate). Interviews with patients participating in the trial will take place at a suitable timepoint after their initial consultation (depending on their diagnosis, likely recovery time and the regimen of any trial intervention), likely around 2 weeks, to understand their experience of being recruited to the trial, trial processes, their views of the intervention and intervention adherence (where relevant). Previous secondary outcome measures from 03/02/2023 to 23/07/2024: Secondary study parameters/endpoints include: 1. Time to first self-report of feeling fully recovered from symptoms related to COVID-19 or COVID-like illness (days) (for Phase IIa type evaluation), measured using self-report for 28 days (or month 3 and 6 if not recovered). 2. Viral clearance (for Phase IIb and III type evaluation) assessed using semi-quantitive PCR at baseline and on days 4, 7 and 14, and impact on biomarkers of illness severity (if this will be an outcome parameter, then this will be specified in the intervention-specific appendix). The impact on biomarkers, for example on illness severity or immunological response is dependent on the specific investigational product (also the method and timepoints are dependent on the investigational product). If this will be an outcome parameter, then this will be specified in the intervention specific appendix of that investigational product. So far, there are no compounds selected for which this will be an outcome parameter. 3. Time to first self-report of return to usual daily activity (days), measured using self-report until the end of the study 4. Presence and severity of COVID-19 or COVID-like-illness symptoms (runny/congested nose, sore throat, cough, fever shortness of breath, fatigue/tiredness, sweats/chills, headache, muscle, joint and/or body aches, loss of taste/smell, diarrhoea, other) as: absent, mild, moderate, severe, measured using a daily diary at day 0-28. 5. Participant-reported overall wellbeing, reported by rating of how well participant feels (scale 0-10) at day 0-28, and after 3 months and 6 months 6. Possible side effects of the IP measured using a daily diary at day 1-28 7. Evaluation of overall safety of the IP by monitoring of AEs for the duration of IP administration and a defined period after the IP administration finishes. The duration of investigational product administration is dependent on the investigational product and will be specified in the intervention specific appendix, for the selected IPs only side effects will be measured, as safety data are already available. 8. The use of additional antiviral medication (yes/no, name of medication), using a daily diary at day 0-28 9. The use of other prescribed and/or OTC medication for the respiratory infection (antibiotics, antiviral medication, ibuprofen, other pain/fever medication, inhaled medication, intranasal medication, other), yes/no, using a daily diary at day 0-28 10. Impact on usual daily activities (work/education, caring for (grand-) children, household activities, sports, social life), as: no, slight, moderate, severe, not applicable, measured at day 1- 28, after 3 and 6 months 11. Complications (i.e. hospitalisation, death) measured using weekly diary at day 7, 14, 21 and 28 or Serious Adverse Event reporting during the entire duration of study participation 12. Healthcare utilisation for COVID-19 or COVID-like-illness (GP and hospital visits) measured using participant diary at day 1-28, months 3 and 6 13. Long-term consequences of COVID-19 or COVID-like-illness (e.g. cough, shortness of breath and/or difficulty breathing, fast heart rate, fatigue, tiredness and/or loss of energy, sleep alterations, loss of smell and/or taste, emotional sensitivity, depression and/or anxiety, concentration problems and/or difficulty thinking, muscle aches and or generalised body pains, diarrhoea and/or stomach pain, other) measured using a follow-up call or electronic questionnaire after 3 and 6 months 14. The incidence of COVID-19 and COVID-like-illness in other members of the household, measured using participants' diaries and/or swabbing the symptomatic household member(s) at daily day 0 - 28, if this will be measured using swabs in household members then timepoint(s) will be specified in the intervention specific appendix Exploratory parameters: 1. Emergence of mutations in causative pathogens in index cases and potentially in household members measured using combined pharyngeal/nasal swabs for participants swabs that are taken at Day 0, 4, 7 and 14 can be used, if this will be measured in household members then timepoint(s) will be specified in the intervention specific appendix 2. Experiences of researchers and network coordinators of setting up the trial in multiple countries, including views on optimising trial delivery, recruitment, and implementation (qualitative study) measured using interviews either remotely (by telephone or online or in person as appropriate). Interviews with researchers and network coordinators will take place throughout the period of ECRAID-Prime prior to trial set up through to completion of recruitment and follow-up of patients. We will aim to include longitudinal interviews, interviewing the same participant at multiple timepoints, where possible, to gain insights into how researchers apply learning to improve trial processes throughout the study 3. Healthcare professionals’ views and experience of taking part in the trial (in the context of a pandemic), the novel trial design, recruiting patients and views on the intervention(s) (qualitative study) measured using interviews either remotely (by telephone or online or in person as appropriate). Interviews with healthcare professionals will take place throughout the trial and will focus on key timepoints such as start of recruitment and introduction of a new intervention arm. 4. Patient views and experiences of taking part in the trial and trial interventions, including how they conceptualise their illness and recovery (qualitative study) measured using interviews either remotely (by telephone or online or in person as appropriate). Interviews with patients participating in the trial will take place at a suitable timepoint after their initial consultation (depending on their diagnosis, likely recovery time and the regimen of any trial intervention), likely around 2 weeks, to understand their experience of being recruited to the trial, trial processes, their views of the intervention and intervention adherence (where relevant). Previous secondary outcome measures as of 04/01/2023 to 03/02/2023: Secondary study parameters/endpoints include: 1. Viral clearance (for Phase IIb and III type evaluation) 2. Time to first self-report of return to usual daily activity (days), measured using self-report until the end of the study 3. Presence and severity of COVID-19 or COVID-like-illness symptoms (runny/congested nose, sore throat, cough, fever shortness of breath, fatigue/tiredness, sweats/chills, headache, muscle, joint and/or body aches, loss of taste/smell, diarrhoea, other) as: absent, mild, moderate, severe, measured using a daily diary at day 0-28. 4. Participant-reported overall wellbeing, reported by rating of how well participant feels (scale 0-10) at day 0-28, and after 3 months and 6 months 5. Possible side effects of the IP measured using a daily diary at day 1-28 6. Evaluation of overall safety of the IP by monitoring of AEs for the duration of IP administration and a defined period after the IP administration finishes. The duration of investigational product administration is dependent on the investigational product and will be specified in the intervention specific appendix, for the selected IPs only side effects will be measured, as safety data are already available. 7. Impact on usual daily activities (work/education, caring for (grand-) children, household activities, sports, social life), as: no, slight, moderate, severe, not applicable, measured at day 1-28, after 3 and 6 months 8. Complications (i.e. hospitalisation, death) measured using weekly diary at day 7, 14, 21 and 28 or Serious Adverse Event reporting during the entire duration of study participation 9. Healthcare utilisation for COVID-19 or COVID-like-illness (GP and hospital visits) measured using participant diary at day 1-28, months 3 and 6 10. Long-term consequences of COVID-19 or COVID-like-illness (e.g. cough, shortness of breath and/or difficulty breathing, fast heart rate, fatigue, tiredness and/or loss of energy, sleep alterations, loss of smell and/or taste, emotional sensitivity, depression and/or anxiety, concentration problems and/or difficulty thinking, muscle aches and or generalised body pains, diarrhoea and/or stomach pain, other) measured using a follow-up call or electronic questionnaire after 3 and 6 months 11. The incidence of COVID-19 and COVID-like-illness in other members of the household, measured using participants' diaries and/or swabbing the symptomatic household member(s) at daily day 0 - 28, if this will be measured using swabs in household members then timepoint(s) will be specified in the intervention specific appendix Exploratory parameters: 1. Emergence of mutations in causative pathogens in index cases and potentially in household members measured using combined pharyngeal/nasal swabs for participants swabs that are taken at Day 0, 4, 7 and 14 can be used, if this will be measured in household members then timepoint(s) will be specified in the intervention specific appendix 2. Experiences of researchers and network coordinators of setting up the trial in multiple countries, including views on optimising trial delivery, recruitment, and implementation (qualitative study) measured using interviews either remotely (by telephone or online or in person as appropriate). Interviews with researchers and network coordinators will take place throughout the period of ECRAID-Prime prior to trial set up through to completion of recruitment and follow-up of patients. We will aim to include longitudinal interviews, interviewing the same participant at multiple timepoints, where possible, to gain insights into how researchers apply learning to improve trial processes throughout the study 3. Healthcare professionals’ views and experience of taking part in the trial (in the context of a pandemic), the novel trial design, recruiting patients and views on the intervention(s) (qualitative study) measured using interviews either remotely (by telephone or online or in person as appropriate). Interviews with healthcare professionals will take place throughout the trial and will focus on key timepoints such as start of recruitment and introduction of a new intervention arm. 4. Patient views and experiences of taking part in the trial and trial interventions, including how they conceptualise their illness and recovery (qualitative study) measured using interviews either remotely (by telephone or online or in person as appropriate). Interviews with patients participating in the trial will take place at a suitable timepoint after their initial consultation (depending on their diagnosis, likely recovery time and the regimen of any trial intervention), likely around 2 weeks, to understand their experience of being recruited to the trial, trial processes, their views of the intervention and intervention adherence (where relevant). Previous secondary outcome measures: Secondary study parameters/endpoints include: 1. Time to first self-report of return to usual daily activity (days), measured using self-report until the end of the study 2. Presence and severity of COVID-19 or COVID-like-illness symptoms (runny/congested nose, sore throat, cough, fever shortness of breath, fatigue/tiredness, sweats/chills, headache, muscle, joint and/or body aches, loss of taste/smell, diarrhoea, other) as: absent, mild, moderate, severe, measured using a daily diary at day 0-28. 3. Participant-reported overall wellbeing, reported by rating of how well participant feels (scale 0-10) at day 0-28, and after 3 months and 6 months 4. Possible side effects of the IP measured using a daily diary at day 1-28 5. Evaluation of overall safety of the IP by monitoring of AEs for the duration of IP administration and a defined period after the IP administration finishes. The duration of investigational product administration is dependent on the investigational product and will be specified in the intervention specific appendix, for the selected IPs only side effects will be measured, as safety data are already available. 6. Impact on usual daily activities (work/education, caring for (grand-) children, household activities, sports, social life), as: no, slight, moderate, severe, not applicable, measured at day 1-28, after 3 and 6 months 7. Complications (i.e. hospitalisation, death) measured using weekly diary at day 7, 14, 21 and 28 or Serious Adverse Event reporting during the entire duration of study participation 8. Healthcare utilisation for COVID-19 or COVID-like-illness (GP and hospital visits) measured using participant diary at day 1-28, months 3 and 6 9. Long-term consequences of COVID-19 or COVID-like-illness (e.g. cough, shortness of breath and/or difficulty breathing, fast heart rate, fatigue, tiredness and/or loss of energy, sleep alterations, loss of smell and/or taste, emotional sensitivity, depression and/or anxiety, concentration problems and/or difficulty thinking, muscle aches and or generalised body pains, diarrhoea and/or stomach pain, other) measured using a follow-up call or electronic questionnaire after 3 and 6 months 10. The incidence of COVID-19 and COVID-like-illness in other members of the household, measured using participants' diaries and/or swabbing the symptomatic household member(s) at daily day 0 - 28, if this will be measured using swabs in household members then timepoint(s) will be specified in the intervention specific appendix Exploratory parameters: 1. Emergence of mutations in causative pathogens in index cases and potentially in household members measured using combined pharyngeal/nasal swabs for participants swabs that are taken at Day 0, 4, 7 and 14 can be used, if this will be measured in household members then timepoint(s) will be specified in the intervention specific appendix 2. Experiences of researchers and network coordinators of setting up the trial in multiple countries, including views on optimising trial delivery, recruitment, and implementation (qualitative study) measured using interviews either remotely (by telephone or online or in person as appropriate). Interviews with researchers and network coordinators will take place throughout the period of ECRAID-Prime prior to trial set up through to completion of recruitment and follow-up of patients. We will aim to include longitudinal interviews, interviewing the same participant at multiple timepoints, where possible, to gain insights into how researchers apply learning to improve trial processes throughout the study 3. Healthcare professionals’ views and experience of taking part in the trial (in the context of a pandemic), the novel trial design, recruiting patients and views on the intervention(s) (qualitative study) measured using interviews either remotely (by telephone or online or in person as appropriate). Interviews with healthcare professionals will take place throughout the trial and will focus on key timepoints such as start of recruitment and introduction of a new intervention arm. 4. Patient views and experiences of taking part in the trial and trial interventions, including how they conceptualise their illness and recovery (qualitative study) measured using interviews either remotely (by telephone or online or in person as appropriate). Interviews with patients participating in the trial will take place at a suitable timepoint after their initial consultation (depending on their diagnosis, likely recovery time and the regimen of any trial intervention), likely around 2 weeks, to understand their experience of being recruited to the trial, trial processes, their views of the intervention and intervention adherence (where relevant). |
| Overall study start date | 01/12/2021 |
| Completion date | 31/12/2025 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | Both |
| Target number of participants | 333 participants per arm (expected +/- 1000 participants in the trial across all arms and all sites) |
| Key inclusion criteria | In order to be eligible to participate in ECRAID-Prime, a participant must (at least) meet all the following criteria (there can be additional intervention-specific inclusion criteria): 1. Participant is ≥18 years of age on the day of inclusion; if people aged <18 years are suitable for inclusion in the evaluation of an investigational product, then this will be described and justified in the relevant, approved intervention-specific appendix 2. Presence of at least two symptoms suggestive of COVID-19 or COVID-like-illness, one respiratory (cough, sore throat, running or congested nose or sinuses, shortness of breath) and one systemic (fever, feeling feverish, sweats/chills or shivering, low energy or tiredness, headache, muscle, joint or body aches, loss of taste and/or smell) 3. Judged by recruiting a medically qualified clinician or research nurse that the illness is due to COVID-19 or COVID-like illness 4. Onset of symptoms less than 7 days (in case earlier treatment is required for a specific investigational product, this will be specified in the intervention-specific appendix) 5. Willing and able to give informed consent for participation in the study 6. Willing and able to comply with all trial procedures 7. Any additional eligibility criteria relevant to women of child-bearing potential including current pregnancy or breastfeeding will be specified in the intervention-specific appendix |
| Key exclusion criteria | A potential participant who meets any of the following criteria will be excluded from participation in ECRAID-Prime (there can be additional intervention-specific exclusion criteria). 1. Requiring admission to the hospital on the day of screening, or inclusion 2. Known allergies or hypersensitivities to any of the components used in the formulation of the investigational product, or the control product 3. Any disease, condition, or disorder that precludes participation in the trial, in the opinion of the person checking eligibility and taking consent 4. Any planned major surgery in the next 28 days 5. Currently participating in a trial of an investigational product |
| Date of first enrolment | 03/10/2024 |
| Date of final enrolment | 31/12/2025 |
Locations
Countries of recruitment
- Belgium
- France
- Georgia
- Germany
- Ireland
- Netherlands
- Poland
- Spain
- United Kingdom
Study participating centres
University Medical Center Utrecht
Heidelberglaan 100
Utrecht
3584 CX
Netherlands
Utrecht
3584 CX
Netherlands
Universitätsklinikum Würzburg
Josef-Schneider-Straße 2 // Haus D7
Würzburg
97080
Germany
Würzburg
97080
Germany
Centre d’Investigation Clinique (CIC) CHU de Limoges
2 Avenue Martin Luther King
Limoges
87042
France
Limoges
87042
France
WGC ‘t Spoor
Kwekerijstraat 75, Borgerhout
Antwerp
2140
Belgium
Antwerp
2140
Belgium
Huisartsenpraktijk Zwaantjes
Antwerpsesteenweg 454, Hoboken
Antwerp
2660
Belgium
Antwerp
2660
Belgium
wijkgezondheidscentrum De Vlier
Truweelstraat 114, Sint-Niklaas
Antwerp
9100
Belgium
Antwerp
9100
Belgium
Huisartsenpraktijk Brig
Robert Vekemansplein 3 bus 1, Boom
Antwerp
2850
Belgium
Antwerp
2850
Belgium
Huisartsen De Poort
Grotesteenweg 186, Berchem
Berchem
2600
Belgium
Berchem
2600
Belgium
huisartsen Wolvenberg
Vredestraat 93
Berchem
2600
Belgium
Berchem
2600
Belgium
praktijkhuis de Grote Rivier
Lanteernhofstraat 106, Deurne
Antwerp
2100
Belgium
Antwerp
2100
Belgium
Villa Medica
Hoek 15-17, Rijkevorstel
Antwerp
2310
Belgium
Antwerp
2310
Belgium
Huisartsengroep Lange Leem
Lange Leemstraat 385
Antwerp
2018
Belgium
Antwerp
2018
Belgium
Huisartsenpraktijk Begijnenstraat
Begijnenstraat 44
Turnhout
2300
Belgium
Turnhout
2300
Belgium
Crescent medical centre
1 The Crescent
Galway
H91 E7FP
Ireland
Galway
H91 E7FP
Ireland
Heights Medical Centre
Castlelawn Heights, Coolough Road, Co. Galway
Galway
H91YR1X
Ireland
Galway
H91YR1X
Ireland
Main Street Clinic
Main street Loughrea
Galway
H62 X252
Ireland
Galway
H62 X252
Ireland
Moyview Family Practice
Dillon Terrace, Ballina, Co. Mayo
Ballina
F26 R9V2
Ireland
Ballina
F26 R9V2
Ireland
Tramore Medical Centre
Summerhill Centre, Tramore, Co. Waterford
Tramore
X91 X90F
Ireland
Tramore
X91 X90F
Ireland
Akademicka Praktyka Medycyny Rodzinnej Bielska
15-269 Bialystok, ul. Mazowiecka 33
bialystok
15-269
Poland
bialystok
15-269
Poland
Medimed
ul.Tuwima 1/2 lok. 2
Bialystok
15-746
Poland
Bialystok
15-746
Poland
Spółka cywilna SILOE Katarzyna Jachimowicz
ul. W Raginisa 87/2
Bialystok
15-156
Poland
Bialystok
15-156
Poland
Poradnia Lekarza Rodzinnego Joanna Redźko-Baszun
ul. Klepacka 4
Bialystok
15-634
Poland
Bialystok
15-634
Poland
NZOZ „Poradnia Rodzinna” Agnieszka Gosk
ul. Ks. St. Andrukiewicza 4 lok 3u
Bialystok
15-204
Poland
Bialystok
15-204
Poland
Centrum Medyczne Kleosin Wieliczko
ul. Zambrowska 14
Bialystok
16-001
Poland
Bialystok
16-001
Poland
Centro de Atencion Primaria Jaume 1
Carrer D/ Felip Pedrell, 2.
Tarragona
43005
Spain
Tarragona
43005
Spain
Centro de Atencion Primaria 17 de setembre
Carrer d'Empúries, S/N
El Prat de Llobregat
08820
Spain
El Prat de Llobregat
08820
Spain
Centro de Atencion Primaria Sant Martí de Provençals
Fluvià, 211
Fluvià
08020
Spain
Fluvià
08020
Spain
Centro de Atencion Primaria Maresme
Camí del Mig. 36
Mataró
08303
Spain
Mataró
08303
Spain
Equip D'atencio Primaria Barcelona Sardenya S.L.P.
Carrer Sardenya 466
Barcelona
08025
Spain
Barcelona
08025
Spain
Medcapital Gldani
138 A. Tsereteli Avenue
Tblisi
0119
Georgia
Tblisi
0119
Georgia
Nuffield Department of Primary Care Health Sciences, University of Oxford
Gibson Building 1st floor
Radcliffe Observatory Quarter
Woodstock Road
Oxford
OX2 6GG
United Kingdom
Radcliffe Observatory Quarter
Woodstock Road
Oxford
OX2 6GG
United Kingdom
Sponsor information
University Medical Center Utrecht
Hospital/treatment centre
Hospital/treatment centre
Heidelberglaan 100
Utrecht
3584 CX
Netherlands
| Phone | +31 (0)887555555 |
|---|---|
| info@umcutrecht.nl | |
| Website | http://www.umcutrecht.nl |
"ROR" |
https://ror.org/0575yy874 |
Funders
Funder type
Government
European Union
No information available
Results and Publications
| Intention to publish date | 30/12/2025 |
|---|---|
| Individual participant data (IPD) Intention to share | Yes |
| IPD sharing plan summary | Stored in non-publicly available repository |
| Publication and dissemination plan | Planned publication in a high-impact peer-reviewed journal |
| IPD sharing plan | Descriptive metadata will be made fully open through a cohort browser. Controlled access, participant-level data will be made available through a controlled access data platform. Restricted access, participant-level data will be made available to internal partners (e.g., statisticians at participating institutions) within the ECRAID-Prime internal network through the UMCU data warehouse infrastructure. Restricted access participant-level data that includes individual identifiers (e.g., birth date) will not be made openly accessible in line with national, European and international legal, ethical and privacy concerns and to ensure that data sharing complies with the GDPR. |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Protocol file | version 5.0 | 22/03/2024 | 09/10/2024 | No | No |
| Protocol file | ISA A version 4.0 |
22/03/2024 | 09/10/2024 | No | No |
| Protocol file | ISA B version 4.0 |
22/03/2024 | 09/10/2024 | No | No |
| Protocol file | ISA C version 4.0 |
22/03/2024 | 09/10/2024 | No | No |
Additional files
Editorial Notes
04/11/2024: Georgia was added to the countries of recruitment. Medcapital Gldani and Nuffield Department of Primary Care Health Sciences, University of Oxford were added to the study participating centres.
09/10/2024: The following changes were made to the trial record:
1. Uploaded protocols v4.0 (not peer-reviewed) as additional files.
2. Uploaded protocol v5.0 (not peer-reviewed) as an additional file.
07/10/2024: The following changes were made to the study record:
1. Eudract/CTIS number updated.
2. The recruitment start date was changed from 01/09/2024 to 03/10/2024.
3. The recruitment end date was changed from 01/06/2025 to 31/12/2025.
4. The overall study end date was changed from 30/06/2025 to 31/12/2025.
23/07/2024: The following changes were made:
1. The primary and secondary outcome measures, study hypothesis, ethics approval, contact details were updated.
2. Universitätsklinikum Würzburg, Centre d’Investigation Clinique (CIC) CHU de Limoges, WGC ‘t Spoor, Huisartsenpraktijk Zwaantjes, wijkgezondheidscentrum De Vlier, Huisartsenpraktijk Brig, Huisartsen De Poort, huisartsen Wolvenberg, praktijkhuis de Grote Rivier, Villa Medica, Huisartsengroep Lange Leem, Huisartsenpraktijk Begijnenstraat, Crescent medical centre, Heights medical centre, Main Street Clinic, Moyview Family Practice, Tramore Medical Centre, Akademicka Praktyka Medycyny Rodzinnej Bielska, Medimed, Spółka cywilna SILOE Katarzyna Jachimowicz, Poradnia Lekarza Rodzinnego Joanna Redźko-Baszun, NZOZ „Poradnia Rodzinna” Agnieszka Gosk, Centrum Medyczne Kleosin Wieliczko, Centro de Atencion Primaria Jaume 1, Centro de Atencion Primaria 17 de setembre, Centro de Atencion Primaria Sant Martí de Provençals, Centro de Atencion Primaria Maresme, Equip D'atencio Primaria Barcelona Sardenya S.L.P. were added to the study participating centres.
3. The recruitment start date was changed from 01/06/2024 to 01/09/2024.
4. The recruitment end date was changed from 01/03/2025 to 01/06/2025.
5. The overall study end date was changed from 30/12/2024 to 30/06/2025.
04/03/2024: The recruitment start date was changed from 01/03/2024 to 01/06/2024.
05/12/2023: The following changes were made:
1. The recruitment start date was changed from 01/12/2023 to 01/03/2024.
2. The recruitment end date was changed from 30/12/2024 to 01/03/2025.
31/10/2023: 2 scientific contacts were added.
03/10/2023: The following changes were made to the trial record:
1. The IRAS number was added.
2. The target number of participants was changed from "333 participants per arm (expected +/- 1700 participants in the trial across all arms and all sites)" to "333 participants per arm (expected +/- 1000 participants in the trial across all arms and all sites)".
3. The recruitment start date was changed from 01/10/2023 to 01/12/2023.
03/07/2023: Contact details updated.
06/06/2023: The following changes were made to the study record:
1. The recruitment start date was changed from 01/06/2023 to 01/10/2023.
2. The recruitment end date was changed from 30/08/2024 to 30/12/2024.
3. The overall study end date was changed from 30/11/2024 to 30/12/2024.
4. The intention to publish date was changed from 30/11/2025 to 30/12/2025.
09/05/2023: A contact was removed.
05/04/2023: The recruitment start date was changed from 01/04/2023 to 01/06/2023.
03/02/2023: The following changes were made to the trial record:
1. The primary outcome measure was changed.
2. The secondary outcome measures were changed.
04/01/2023: The following changes were made to the trial record:
1. The primary outcome measure was changed.
2. The secondary outcome measures were changed.
3. The target number of participants was changed from "135 participants per arm (expected +/- 1500 participants in the trial across all arms and all sites)" to "333 participants per arm (expected +/- 1700 participants in the trial across all arms and all sites)".
4. The recruitment start date was changed from 01/01/2023 to 01/04/2023.
11/11/2022: Trial's existence confirmed by European Commission.
