CARRIAGE study: investigating Staphylococcus aureus nasal carriage
| ISRCTN | ISRCTN10474633 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN10474633 |
| IRAS number | 202688 |
| Secondary identifying numbers | Protocol version 4 - 20/06/2018, IRAS 202688 |
- Submission date
- 11/07/2016
- Registration date
- 20/07/2016
- Last edited
- 27/02/2023
- Recruitment status
- No longer recruiting
- Overall study status
- Ongoing
- Condition category
- Infections and Infestations
Plain English Summary
Background and study aims
Staphylococcus aureus (S. aureus) is a common bacterium with about one person in every three carrying it in their nose, or elsewhere on the skin. Some people carry it all the time, some only now and then, and others never carry it. Currently, we can’t explain why. For most people, carriage of S. aureus is harmless. However, a small number of people are susceptible to S. aureus infections due to a weakened immune system and, in some cases, these infections may be serious and resistant to antibiotic treatment. Understanding why only some people are carriers while others aren’t will help design new ways to prevent and treat such infections. The aim of this study is to investigate why some people carry S. aureus in their nose while others never do. The study will provide a better understanding of the biological, genetic and environmental factors that determine S. aureus carriage. One way to see if a person carries S. aureus is to analyse swabs taken from the nose.
Who can participate?
Healthy volunteers who participated in the, INTERVAL,COMPARE, and STRIDES BioResource (part of the NIHR BioResource) studies.
What does the study involve?
In phase 1, 250 participants are randomly allocated to one of two swabbing frequencies (two versus three swabs). The acceptability of each swabbing frequency is assessed based on participant response rates and participant feedback from an online questionnaire asking about experiences of taking part in the study.
In phase 2 a further 2000 participants are invited to collect nasal swabs. The number of swabs collected is informed by the results of phase 1 (i.e., either two or three). This phase assesses the feasibility of collecting, processing and analysing swabs from large numbers of participants.
In phase 3, participants from the INTERVAL, COMPARE and STRIDES BioResource studies are invited to collect three nasal swabs so that we receive a full sample set from 20,000 participants in total. This is the phase which follows on from phase 1 and is an extension of phase 2 which tested the feasibility of the study design.
What are the possible benefits and risks of participating?
We will not provide any new information or advice to participants based on the samples and data collected during the study; at present, this information has no clinical implications for the participant. As such, involvement in the study will have no direct benefit to participants. However, it is an opportunity for volunteers to support research, which addresses an important public health issue. There are no known risks associated with nasal swabbing. All participants will receive clear written instructions and a link to an online video demonstrating swabbing technique. Nasal swabbing may pose minor risks in individuals with nasal problems or nasal damage and, as such, potential participants who report having such conditions will be excluded from the study.
Where is the study run from?
The study is coordinated by the University of Cambridge and is conducted in the community across England.
When is the study starting and how long is it expected to run for?
September 2016 to September 2023
Who is funding the study?
1. Wellcome Trust
2. UK Research and Innovation (UKRI)
3. Health Data Research (HDR) UK
4. The Isaac Newton Trust
Who is the main contact?
Dr Ewan Harrison, eh439@medschl.cam.ac.uk
Contact information
Public
Cardiovascular Epidemiology Unit
Department of Public Health and Primary Care
University of Cambridge
Strangeways Research Laboratory
Worts Causeway
Cambridge
CB1 8RN
United Kingdom
 ORCID ID |
0000-0003-2720-0507 |
|---|---|
| Phone | +44 (0)1223 336839 |
| eh439@cam.ac.uk |
Study information
| Study design | Two-stage feasibility study with interventional, observational and cross-sectional components followed by the main study phase |
|---|---|
| Primary study design | Observational |
| Secondary study design | Epidemiological study |
| Study setting(s) | Community |
| Study type | Other |
| Participant information sheet | Available on trial website |
| Scientific title | Understanding the biological basis of persistent carriage of Staphylococcus aureus in humans |
| Study acronym | CARRIAGE |
| Study hypothesis | The principal research question is to assess the feasibility and acceptability of protocols for the collection and processing of nasal self-swabs in healthy volunteers to inform a larger proposed study to investigate the biological basis of persistent Staphylococcus aureus (S. aureus) carriage. The secondary research objectives are to assess: 1. The relative participant-acceptability of two vs three weekly nasal swabs 2. The prevalence of persistent S. aureus carriage rates in healthy volunteers 3. Lifestyle and biomarker correlates of persistent nasal carriage and validate associations with previously suggested candidate variants, and to identify new genetic associations (added 19/06/2019) |
| Ethics approval(s) | North West - Lancaster Research Ethics Committee, 27/06/2016, REC reference: 16/NW/0507, IRAS project ID: 202688 |
| Condition | Nasal carriage of Staphylococcus aureus |
| Intervention | Current interventions as of 24/02/2023: Phase 1 and 2 of the study will involve the recruitment of participants who have taken part in previous studies (INTERVAL: ISRCTN24760606) and have agreed to be invited to other studies organised by NHS Blood and Transplant and/or University of Cambridge and/or University of Oxford. Phase 3 (main study) will, in addition to INTERVAL, include participants from the COMPARE study (ISRCTN90871183) and STRIDES BioResource study. In phase 1: Participant acceptability of collecting two versus three swabs will be compared in approximately 250 participants (125 per arm). Prior to invitation, there will be a 1:1 random allocation to each of the swabbing frequencies; simple block randomisation stratified by age and gender will be used. The acceptability of each protocol will be based on participant response rates to the two- and three-swab protocol and participant feedback from an online questionnaire asking about experiences of taking part in the study – now complete. Phase 2: A further (approximately) 2000 participants will be invited to collect nasal swabs. The number of swabs collected will be informed by the results of phase 1 (i.e. either two or three). This phase will assess, more generally, the operational feasibility of collecting, processing and analysing swabs in large numbers of participants. It will also assess lifestyle and biomarker correlates of persistent nasal S. aureus carriage. – now complete. In Phase 3: This is the main study phase where we will consent enough participants to retrieve a full sample set (3 swabs) from 20,000 participants. . This phase will assess, more generally, the operational feasibility of collecting, processing and analysing swabs in large numbers of participants. It will also assess lifestyle and biomarker correlates of persistent nasal S. aureus carriage and to identify new genetic associations. In all phases of the study prevalence rates of S. aureus carriage will be assessed. Participants joining the study will be asked to complete an online baseline questionnaire designed to collect health and lifestyle information which may be relevant to predisposition to S. aureus carriage. On completion of their questionnaire, participants will be sent a nasal swabbing pack in the post and asked to return their first swab immediately and subsequent swabs at weekly intervals. Once participants have returned all swabs they will be sent an online feedback questionnaire about their experiences of taking the swabs and participating in the study. The study will be administered by the University of Cambridge and will be conducted in the community across England. _____ Previous interventions as of 19/06/2019: Phase 1 and 2 of the study will involve the recruitment of participants who have taken part in previous studies (INTERVAL: ISRCTN24760606) and have agreed to be invited to other studies organised by NHS Blood and Transplant and/or University of Cambridge and/or University of Oxford. Phase 2 (extended) (main study) will, in addition to INTERVAL, include participants from the COMPARE study (ISRCTN90871183). In phase 1: Participant acceptability of collecting two versus three swabs will be compared in approximately 250 participants (125 per arm). Prior to invitation, there will be a 1:1 random allocation to each of the swabbing frequencies; simple block randomisation stratified by age and gender will be used. The acceptability of each protocol will be based on participant response rates to the two- and three-swab protocol and participant feedback from an online questionnaire asking about experiences of taking part in the study – now complete. Phase 2: A further (approximately) 2000 participants will be invited to collect nasal swabs. The number of swabs collected will be informed by the results of phase 1 (i.e. either two or three). This phase will assess, more generally, the operational feasibility of collecting, processing and analysing swabs in large numbers of participants. It will also assess lifestyle and biomarker correlates of persistent nasal S. aureus carriage. – now complete. In Phase 2 (extended): This is the main study phase where approximately 20,000 participants will be invited to take part. This phase will assess, more generally, the operational feasibility of collecting, processing and analysing swabs in large numbers of participants. It will also assess lifestyle and biomarker correlates of persistent nasal S. aureus carriage and to identify new genetic associations. In all phases of the study prevalence rates of S. aureus carriage will be assessed. Participants joining the study will be asked to complete an online baseline questionnaire designed to collect health and lifestyle information which may be relevant to predisposition to S. aureus carriage. On completion of their questionnaire, participants will be sent a nasal swabbing pack in the post and asked to return their first swab immediately and subsequent swabs at weekly intervals. Once participants have returned all swabs they will be sent an online feedback questionnaire about their experiences of taking the swabs and participating in the study. The study will be administered by the University of Cambridge and will be conducted in the community across England. _____ Previous interventions: Both stages of the study will involve the recruitment of participants who have taken part in a previous study (INTERVAL: ISRCTN24760606) and have agreed to be invited to other studies organised by NHS Blood and Transplant and/or University of Cambridge and/or University of Oxford. In stage 1: Participant acceptability of collecting two versus three swabs will be compared in approximately 250 participants (125 per arm). Prior to invitation, there will be a 1:1 random allocation to each of the swabbing frequencies; simple block randomisation stratified by age and gender will be used. The acceptability of each protocol will be based on participant response rates to the two- and three-swab protocol and participant feedback from an online questionnaire asking about experiences of taking part in the study. In Stage 2: A further (approximately) 2000 participants will be invited to collect nasal swabs. The number of swabs collected will be informed by the results of Stage 1 (i.e. either two or three). This stage will assess, more generally, the operational feasibility of collecting, processing and analysing swabs in large numbers of participants. It will also assess lifestyle and biomarker correlates of persistent nasal S. aureus carriage. In both stages of the study prevalence rates of S. aureus carriage will be assessed. Participants joining the study will be asked to complete an online baseline questionnaire designed to collect health and lifestyle information which may be relevant to predisposition to S. aureus carriage. On completion of their questionnaire, participants will be sent a nasal swabbing pack in the post and asked to return their first swab immediately and subsequent swabs at weekly intervals. Once participants have returned all swabs they will be sent an online feedback questionnaire about their experiences of taking the swabs and participating in the study. The study will be administered by the University of Cambridge and will be conducted in the community across England. |
| Intervention type | Other |
| Primary outcome measure | Current primary outcome measure as of 19/06/2019: 1. To assess the feasibility of collecting, processing and analysing nasal swabs in large numbers of participants. 2. To assess the prevalence of persistent S. aureus nasal carriage rates in healthy volunteers. 3. To assess lifestyle and biomarker correlates of persistent nasal S. aureus carriage and validate associations with previously suggested candidate genetic variants and to identify new genetic associations. _____ Previous primary outcome measure: Response rates to nasal swab collections including differences in response rates to initial invitation to provide two vs three swabs and compliance to the collection and return of two vs three swabs |
| Secondary outcome measures | Current secondary outcome measures as of 27/02/2023: Phases 1 & 2: 1. Participant feedback from the online questionnaire administered to participants on completion of their involvement in the study. Data collected will include binary (yes/no), Likert Scale and free text responses 2. Operational outcomes: the success of operational procedures will be reviewed including: posting of nasal swabbing packs, sample receipt at the processing laboratory and laboratory methods for sample processing and analysis Phase 3 1. To assess the feasibility of collecting, processing and analysing nasal swabs in large numbers of participants. 2. To assess the prevalence of persistent S. aureus nasal carriage rates in healthy volunteers. 3. To assess lifestyle and biomarker correlates of persistent nasal S. aureus carriage and validate associations with previously suggested candidate genetic variants and to identify new genetic associations. _____ Previous secondary outcome measures as of 19/06/2019: Phases 1 & 2: 1. Participant feedback from the online questionnaire administered to participants on completion of their involvement in the study. Data collected will include binary (yes/no), Likert Scale and free text responses 2. Operational outcomes: the success of operational procedures will be reviewed including: posting of nasal swabbing packs, sample receipt at the processing laboratory and laboratory methods for sample processing and analysis _____ Previous secondary outcome measures: Stages 1 & 2: 1. Participant feedback from the online questionnaire administered to participants on completion of their involvement in the study. Data collected will include binary (yes/no), Likert Scale and free text responses 2. Prevalence of persistent nasal carriage of Staphylococcus aureus in healthy volunteers. The point prevalence of carriage will be calculated using the first swabs returned by participants. Persistent carriage will be defined based on two positive swabs in participants randomised to the two-swab protocol and three positive swabs in participants randomised to the three-swab protocol. 3. Operational outcomes: the success of operational procedures will be reviewed including: posting of nasal swabbing packs, sample receipt at the processing laboratory and laboratory methods for sample processing and analysis Stage 2: Lifestyle, biomarker and genetic correlates of persistent S. aureus carriage assessed using either logistic or linear regression models |
| Overall study start date | 01/09/2016 |
| Overall study end date | 27/06/2026 |
Eligibility
| Participant type(s) | Healthy volunteer |
|---|---|
| Age group | Adult |
| Sex | Both |
| Target number of participants | Phase 1: 250, Phase 2: 2,000, Main phase: 20,000 |
| Participant inclusion criteria | Current inclusion criteria as of 24/02/2023: 1. Be already enrolled in the INTERVAL, COMPARE or STRIDES BioResource studies 2. Have an email address for study participation 3. Reside in mainland England 4. Have a good understanding of the English language, both written and oral (study materials are not tailored to support non-English language speakers) _____ Previous participant inclusion criteria as of 19/06/2019: 1. Be already enrolled in the INTERVAL or COMPARE studies 2. Have an email address for study participation 3. Reside in mainland England 4. Have a good understanding of the English language, both written and oral (study materials are not tailored to support non-English language speakers) _____ Previous participant inclusion criteria: 1. Be already enrolled in the INTERVAL study 2. Have an email address for study participation 3. Reside in mainland England 4. Have a good understanding of the English language, both written and oral (study materials are not tailored to support non-English language speakers) |
| Participant exclusion criteria | Current exclusion criteria as of 24/02/2023: 1. Received three invitations from the INTERVAL, COMPARE or STRIDES BioResource research study teams to take part in other studies in the past year 2. Withdrawn their consent to take part in the INTERVAL,COMPARE or STRIDES BioResource studies 3. Any abnormalities or ongoing medical conditions that affect the nose (e.g. nosebleeds, nasal polyps, rhinitis, etc) 4. Undergone nasal surgery in the last year 5. Nasal fracture in the last year _____ Previous participant exclusion criteria as of 19/06/2019: 1. Received three invitations from the INTERVAL or COMPARE research study teams to take part in other studies in the past year 2. Withdrawn their consent to take part in the INTERVAL or COMPARE studies 3. Any abnormalities or ongoing medical conditions that affect the nose (e.g. nosebleeds, nasal polyps, rhinitis, etc) 4. Undergone nasal surgery in the last year 5. Nasal fracture in the last year ______ Previous participant exclusion criteria: 1. Have received 3 invitations from the INTERVAL research study team to take part in other studies in the past year 2. Have withdrawn their consent to take part in the INTERVAL study 3. Have any abnormalities or ongoing medical conditions that affect the nose (e.g. nosebleeds, nasal polyps, rhinitis, etc) 4. Have undergone nasal surgery in the last year 5. Have had a nasal fracture in the last year 6. Are not going to be available to take part in the study during the next two months due to reasons such as an extended holiday |
| Recruitment start date | 19/09/2016 |
| Recruitment end date | 31/12/2023 |
Locations
Countries of recruitment
- England
- United Kingdom
Study participating centres
Box 157, level 5
Addenbrooke's Hospital
Hills Road
Cambridge
CB2 0QQ
United Kingdom
Heart and Lung Research Institute
Papworth Road
Cambridge
CB2 0BB
United Kingdom
Sponsor information
University/education
School of Clinical Medicine
Addenbrooke's Hospital Hills Road
Cambridge
CB2 0SP
England
United Kingdom
"ROR" |
https://ror.org/013meh722 |
|---|
Funders
Funder type
Charity
Private sector organisation / International organizations
- Location
- United Kingdom
Government organisation / National government
- Alternative name(s)
- UKRI
- Location
- United Kingdom
No information available
Private sector organisation / Universities (academic only)
- Location
- United Kingdom
Results and Publications
| Intention to publish date | 31/12/2024 |
|---|---|
| Individual participant data (IPD) Intention to share | Yes |
| IPD sharing plan summary | Available on request |
| Publication and dissemination plan | The findings from this study will be written up for publication in scientific journals and presentation to other researchers. In due course we will also provide details of the findings of the study on the CARRIAGE website. Anonymous information and samples may be made available on request to researchers who have relevant scientific and ethics approvals for their planned research. |
| IPD sharing plan | Not provided at time of registration |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| HRA research summary | 28/06/2023 | No | No |
Editorial Notes
27/02/2023: The secondary outcome measures were changed.
24/02/2023: The following changes were made to the trial record:
1. The acronym was added.
2. The overall end date was changed from 10/09/2021 to 27/06/2026.
3. The recruitment end date was changed from 06/08/2021 to 31/12/2023.
4. The intention to publish date was changed from 30/06/2022 to 31/12/2024.
5. The interventions were changed.
6. The inclusion criteria were changed.
7. The exclusion criteria were changed.
8. The plain English summary was updated to reflect these changes.
09/07/2020: The trial contact details have been made publicly visible.
19/06/2019: The following changes were made to the trial record:
1. The recruitment end date was changed from 01/05/2017 to 06/08/2021.
2. The overall end date was changed from 30/06/2017 to 10/09/2021.
3. The intention to publish date was changed from 30/06/2017 to 30/06/2022.
4. The plain English summary was updated.
5. The address of the public contact was updated from "Department of Medicine, University of Cambridge, Box 157, level 5, Addenbrooke's Hospital, Hills Road, Cambridge, CB2 0QQ" to "Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Strangeways Research Laboratory, Worts Causeway, Cambridge, CB1 8RN".
6. The funder name was changed from "University of Cambridge (UK)" to "Wellcome Trust, UK Research and Innovation (UKRI), Health Data Research (HDR) UK and the Isaac Newton Trust"
7. The protocol /serial number was changed from "Protocol version 1 - 15/06/2016" to "Protocol version 4 - 20/06/2018".
8. The study hypothesis was updated.
9. The study design was changed from "Two-stage feasibility study with interventional, observational and cross-sectional components" to "Two-stage feasibility study with interventional, observational and cross-sectional components followed by the main study phase".
10. The primary study design was changed from "interventional" to "observational".
11. The secondary study design was changed from "randomised controlled trial" to "epidemiological study".
12. The participant information sheet was made available on the study website.
13. The interventions were changed.
14. The primary outcome measure was changed.
15. The secondary outcome measures were changed.
16. The participant inclusion criteria were changed.
17. The participant exclusion criteria were changed.
18. The target number of participants was changed from "Phase 1: 250, Phase 2: 2000" to "Phase 1: 250, Phase 2: 2,000, Main phase 20,000".
