CandiRes - Understanding how receiving antifungal medications can lead to Candida yeast drug resistance among patients treated in intensive care
| ISRCTN | ISRCTN14165977 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN14165977 |
| IRAS number | 305864 |
| Secondary identifying numbers | IRAS 305864, CPMS 51121 |
- Submission date
- 24/11/2021
- Registration date
- 29/11/2021
- Last edited
- 12/11/2024
- Recruitment status
- Recruiting
- Overall study status
- Ongoing
- Condition category
- Infections and Infestations
Plain English Summary
Background and study aims
Candida is a yeast (a type of fungus) that normally lives on the skin and in the gut, without causing any harm. If it grows out of control, Candida can cause infections like thrush. If it enters the bloodstream or some internal organs, Candida can cause serious infections. The risk of serious infection with Candida is higher for people admitted to the ICU and those with a suppressed immune system. Around 1 in 20 people admitted to the ICU will develop a bloodstream infection from Candida. Candida infections are treated with antifungal medications. Some types of Candida can become resistant to antifungal drugs, making treatment more difficult. Just like with antibiotics, the overuse of antifungal medications is one of the drivers of higher resistance to these drugs. We do not have much information about how Candida develops resistance in the ICU, and about the impact of antifungal drugs on this development. It is hope that the results of this study will help to improve tools to identify drug resistance, identify whether a treatment for Candida is working in a given patient, and establish a way to assess whether treatment for a Candida bloodstream infection is working. This could allow researchers to better study antifungal drugs within clinical trials.
Who can participate?
Patients aged 18 years and over who have been admitted to the ICU and who are more likely to receive antifungal treatment, for example because they are receiving antibiotics.
What does the study involve?
Participants' medical care will not change. The following information will be collected from the participants' medical records: demographic information on age and gender, clinical information regarding length of ICU and hospital stay, illness severity, use of antifungal drugs, risk factors for Candida infection. A blood sample will be collected on the day of study enrolment. Twice weekly, swabs from the mouth and the skin around the anus will be taken and tested for Candida. For participants who develop a serious Candida infection during the study, extra samples will be taken (from the blood or from any drain that might have been inserted for clinical reasons).
What are the possible benefits and risks of participating?
There are no direct benefits to the participants from participating. Taking swabs of the mouth and skin do not pose any risk. Blood sampling will be very limited in volume and will be performed from a central or arterial line whenever possible, to avoid any discomfort.
Where is the study run from?
St George's, University of London (UK)
When is the study starting and how long is it expected to run for?
November 2021 to March 2027
Who is funding the study?
1. Pfizer (UK)
2. Medical Research Foundation UK
Who is the main contact?
Dr Tihana Bicanic, tbicanic@sgul.ac.uk
Contact information
Scientific
Institute of Infection and Immunity
Cranmer Terrance
Tooting
London
SW17 0RE
United Kingdom
 ORCID ID |
0000-0002-2676-838X |
|---|---|
| Phone | +44 (0)2087255613 |
| tbicanic@sgul.ac.uk |
Study information
| Study design | Prospective observational cohort study |
|---|---|
| Primary study design | Observational |
| Secondary study design | Cohort study |
| Study setting(s) | Hospital |
| Study type | Other |
| Participant information sheet | Not available in web format, please use contact details to request a participant information sheet |
| Scientific title | Relationship of antifungal exposure to emergence of Candida resistance in Intensive Care patients: a multi-site cohort study |
| Study acronym | CandiRes |
| Study hypothesis | 1. Antifungal use impacts local fungal ecology, and acts a driver for the micro-evolution of resistance. 2. Patients develop invasive candidiasis in critical care with their colonising flora. 3. Serial quantitative measurements (Candida CFU/ml, time to culture positivity, beta-D-glucan [BDG]) are a feasible marker of microbiological treatment response. |
| Ethics approval(s) | Approved 23/11/2021, HRA and Health and Care Research Wales (HCRW, Health and Care Research Wales Support and Delivery Centre, Castlebridge 4, 15-19 Cowbridge Road East, Cardiff, CF11 9AB, UK; +44 2920 230457; HCRW.approvals@wales.nhs.uk) ref: 21/WA/0370 |
| Condition | Antifungal resistance in Candida among ICU patients |
| Intervention | Current interventions as of 25/08/2023: Participants will undergo: - a baseline blood sample (for beta-D-glucan) - twice weekly oral and perianal skin swab for Candida spp. Participants who develop suspected or confirmed invasive candidiasis will have additional serial sampling: - Serial blood sampling for participants with candidaemia (for BDG, culture, Candida quantification, drug level) - Serial drain fluid sample for participants with deep-seated candidiasis and a drain inserted for clinical reasons. - Serial urine samples for participants with deep-seated candidiasis and a urinary catheter for clinical reasons. For each participant, the end of the study is defined as date of ICU discharge or D30 from study enrolment (whichever is later). _____ Previous interventions: Participants will undergo: - a baseline blood sample (for beta-D-glucan) - twice weekly oral and perianal skin swab for Candida spp. Participants who develop invasive candidiasis will have additional serial sampling: - Serial blood sampling for participants with candidaemia (for BDG, culture, Candida quantification, drug level) - Serial drain fluid sample for participants with deep-seated candidiasis and a drain inserted for clinical reasons. Added 07/11/2022: - Serial urine samples for participants with deep-seated candidiasis and a urinary catheter for clinical reasons. For each participant, the end of the study is defined as date of ICU discharge or D30 from study enrolment (whichever is later). |
| Intervention type | Other |
| Primary outcome measure | Colonisation and invasive infection with azole or echinocandin-resistant Candida spp. (e.g. C. glabrata; C. parapsilosis; C. auris) measured using MALDI-ToF mass spectrometry and resistance profiling at the end of follow up |
| Secondary outcome measures | Measured at end of follow-up unless otherwise noted: 1. Invasive candidiasis, rationale and duration of antifungal therapy, measured using EORTC diagnostic classification at the end of follow-up 2. Isolate antifungal tolerance, measured using change in isolate MIC and supra-MIC growth measured according to CLSI standards at end of follow-up 3. Emergence of genetic mutations associated with antifungal resistance, measured using genetic analysis at end of follow-up 4. Mycological clearance in candidaemic patients treated with antifungals, measured using rate of decline in CFU/BDG/time-to-culture-positivity at 12 h, 24 h, 36 h, 48 h, 72 h and D7 from diagnosis of candidaemia. 5. Exploratory: relationship between Candida resistance phenotype and genotype, PK and PD in candidaemia, measured using MIC, tolerance, antifungal drug levels and mycological clearance at 12 h, 24 h, 36 h, 48 h, 72 h and D7 from diagnosis of candidaemia 6. In-hospital mortality measured using patient records at end of follow-up |
| Overall study start date | 01/11/2021 |
| Overall study end date | 31/03/2027 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | Both |
| Target number of participants | 520 |
| Participant inclusion criteria | Current inclusion criteria as of 12/11/2024: 1. Age ≥18 years 2. Currently receiving intravenous antibiotics 3. One or more of the following Candida risk factors: 3.1. Abdominal surgery in the last 4 weeks 3.2. Upper gastrointestinal/mediastinal perforation or surgery in the last 4 weeks 3.3. Liver failure 3.4. Haematological malignancy 3.5. Previous bone marrow or solid organ transplant 3.6. Neutropenia (neutrophils < 0.5*10e9/l) 3.7. Receipt of an immunosuppressive drug (including corticosteroids, chemotherapy, immune-modulators) 3.8. Total parenteral nutrition (TPN) 3.9. Renal replacement therapy 3.10. Extracorporeal membrane oxygenation (ECMO) 4. Suspected or confirmed invasive candidiasis _____ Previous inclusion criteria: 1. Age ≥18 years 2. Currently receiving intravenous antibiotics 3. One or more of the following Candida risk factors: 3.1. Abdominal surgery in the last 4 weeks 3.2. Upper gastrointestinal/mediastinal perforation or surgery in the last 4 weeks 3.3. Liver failure 3.4. Haematological malignancy 3.5. Previous bone marrow or solid organ transplant 3.6. Neutropenia (neutrophils < 0.5*10e9/l) 3.7. Receipt of an immunosuppressive drug (including corticosteroids, chemotherapy, immune-modulators) 3.8. Total parenteral nutrition (TPN) 3.9. Renal replacement therapy 3.10. Extracorporeal membrane oxygenation (ECMO) 4. Suspected invasive candidiasis (added 25/08/2023) |
| Participant exclusion criteria | Expected ICU length of stay <48 h |
| Recruitment start date | 06/12/2021 |
| Recruitment end date | 31/07/2027 |
Locations
Countries of recruitment
- England
- United Kingdom
- Wales
Study participating centres
London
SE1 9RT
United Kingdom
London
SW17 0RE
United Kingdom
London
SE5 9RS
United Kingdom
Fazakerley Hospital
Lower Lane
Liverpool
L9 7AL
United Kingdom
Cardiff
CF14 4XW
United Kingdom
Sponsor information
University/education
Joint Research and Enterprise Services (JRES)
Ground Floor Jenner Wing
St George's, University of London
London
SW17 0RE
England
United Kingdom
| Phone | +44 (0)2087254986 |
|---|---|
| researchgovernance@sgul.ac.uk | |
| Website | https://www.sgul.ac.uk/ |
"ROR" |
https://ror.org/039zedc16 |
Funders
Funder type
Industry
Government organisation / For-profit companies (industry)
- Alternative name(s)
- Pfizer Inc., Pfizer Consumer Healthcare, Davis, Charles Pfizer & Company, Warner-Lambert, King Pharmaceuticals, Wyeth Pharmaceuticals, Seagen
- Location
- United States of America
No information available
Results and Publications
| Intention to publish date | 31/08/2027 |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Data sharing statement to be made available at a later date |
| Publication and dissemination plan | The study findings will be presented at national and relevant international meetings with abstract publication, and published in high impact peer-reviewed journals, with media coverage where applicable, so that findings and their implications quickly reach all of relevant UK clinical communities and can be translated into policy. This will be facilitated by our investigator group which includes key individuals linked to Infection, Mycology and Intensive Care societies, laboratory networks, professional bodies, NHS England antifungal CQUIN committee and patient/relative groups across a wide range of responsibilities relevant to the management of fungal infection and intensive care in the NHS. |
| IPD sharing plan | The current data sharing plans for this study are unknown and will be available at a later date |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| HRA research summary | 28/06/2023 | No | No |
Editorial Notes
12/11/2024: The following changes were made to the trial record:
1. The inclusion criteria were changed.
2. The target number of participants was changed from 400 to 520.
3. The recruitment end date was changed from 31/07/2024 to 31/07/2027.
4. The study participating centre University Hospital of Wales was added.
13/02/2024: The following changes were made to the study record:
1. The overall study end date was changed from 31/07/2024 to 31/03/2027.
2. The intention to publish date was changed from 31/08/2023 to 31/08/2027.
09/01/2024: The following changes were made to the study record:
1. The recruitment end date was changed from 30/11/2023 to 31/07/2024.
2. The overall end date was changed from 30/11/2023 to 31/07/2024.
25/08/2023: The following changes were made to the trial record:
1. The overall end date was changed from 31/03/2023 to 30/11/2023.
2. The recruitment end date was changed from 31/03/2023 to 30/11/2023.
3. The interventions were changed.
4. The inclusion criteria were updated.
08/11/2022: The following changes were made to the trial record:
1. The overall end date was changed from 04/11/2022 to 31/03/2023.
2. The plain English summary was updated to reflect these changes.
07/11/2022: The following changes were made to the trial record:
1. The recruitment end date was changed from 04/10/2022 to 31/03/2023.
2. The target number of participants was changed from 300 to 400.
3. The interventions were updated.
4. Aintree University Hospital was added as a trial participating centre.
5. The intention to publish date was changed from 06/01/2023 to 31/08/2023.
01/09/2022: The following changes were made to the trial record:
1. The recruitment end date was changed from 30/04/2022 to 04/10/2022.
2. The intention to publish date was changed from 01/05/2023 to 06/01/2023.
10/05/2022: The following changes were made to the trial record:
1. The overall end date was changed from 30/05/2022 to 04/11/2022.
2. The intention to publish date was changed from 01/11/2022 to 01/05/2023.
3. The plain English summary was updated to reflect these changes.
10/01/2022: Internal review.
07/12/2021: Internal review.
25/11/2021: Trial's existence confirmed by NHS HRA.
