Vaccine Response On/off Methotrexate (VROOM): does temporarily suspending methotrexate treatment for two weeks enhance COVID-19 vaccine response?
| ISRCTN | ISRCTN11442263 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN11442263 |
| Secondary identifying numbers | CPMS 50297, v1.0 |
- Submission date
- 22/07/2021
- Registration date
- 23/08/2021
- Last edited
- 25/01/2024
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Musculoskeletal Diseases
Plain English Summary
Background and study aims
The purpose of the VROOM study is to find out if an individual’s response to a vaccine can be improved. Specifically the VROOM study will aim to recruit individuals who have inflammatory conditions such as rheumatoid arthritis and psoriasis and routinely take a drug called methotrexate. The individuals needed for the study are these individuals and specifically those who are invited to and accept an invitation to have a booster vaccination against COVID-19 from the NHS vaccination programme.
Doctors and scientists believe there is a small amount of evidence that if individuals temporarily stop taking their methotrexate for the two weeks around when they receive their COVID-19 booster- it may improve their body’s (immune) response. The study will also help understand the way in which methotrexate dampens the immune response to vaccines.
Methotrexate is the first-line treatment for inflammatory conditions such as rheumatoid arthritis and psoriasis. It does a good job at controlling such diseases but it also reduces the body’s ability to fight infections. People taking methotrexate also don’t get great responses to vaccines such as those against the flu and pneumonia. Better immunity usually means a better chance of not getting infected and fighting the virus if infected. Because there is no clear evidence on whether to halt or continue methotrexate during COVID-19 vaccinations, specialists have given conflicting advice that has confused patients. There is an opportunity to answer this question during the booster vaccinations in winter 2021.
Who can participate?
We will invite 560 people with inflammatory conditions such as rheumatoid arthritis and psoriasis receiving methotrexate to take part in our study looking at vaccine response in those who continue to take their methotrexate as usual or who take a 2-week break from taking their methotrexate around their COVID-19 booster vaccination.
What does the study involve?
Participants will be invited to 3 hospital visits to give some data and a small blood sample at each visit.
What are the possible benefits and risks of participating?
We hope that the valuable information from this study will give the NHS and other countries a clear answer to the question of whether temporarily stopping methotrexate for 2 weeks around the time of COVID-19 booster vaccination improves the vaccine response. We cannot promise that the study will benefit those that participate directly, but the information generated has the potential to benefit all those with inflammatory conditions who continue to be vaccinated against COVID-19 in the future. Thus, the results of this study may benefit those that participate in the future.
There is a small risk of a flare in a participant's inflammatory condition on interrupting methotrexate treatment for two weeks. However, all participants can access treatment for any flare-ups as usual.
Where is the study run from?
The study is sponsored by the University of Nottingham (UK) and runs from the Oxford Clinical Trials Research Unit (OCTRU), a UKCRC-registered CTU.
When is the study starting and how long is it expected to run for?
From July 2021 to September 2022
Who is funding the study?
National Institute for Health Research (NIHR) Efficacy and Mechanism Evaluation Programme (UK)
Who is the main contact?
VROOM study team
vroom@ndorms.ox.ac.uk
Contact information
Public
VROOM Trial Manager
OCTRU, Botnar Research Centre
NDORMS
University of Oxford
Old Road
Headington
OX3 7LD
United Kingdom
| Phone | +44 (0)1865 612661 |
|---|---|
| vroom@ndorms.ox.ac.uk |
Scientific
Room A21 Clinical Sciences Building
Nottingham City Hospital
Hucknall Road
Nottingham
NG5 1PB
United Kingdom
 ORCID ID |
0000-0003-0121-4919 |
|---|---|
| Phone | +44 (0)1158231392 |
| abhishek.abhishek@nottingham.ac.uk |
Study information
| Study design | Multi-centre interventional randomized controlled trial |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Hospital |
| Study type | Treatment |
| Participant information sheet | Not available in web format, please use contact details (vroom@ndorms.ox.ac.uk) to request a participant information sheet |
| Scientific title | A multi-centre randomised controlled trial examining the effects of temporarily suspending low-dose methotrexate treatment for two weeks after SARS-CoV-2 vaccine booster on vaccine response in immunosuppressed adults with inflammatory conditions, including a nested mechanistic sub-study |
| Study acronym | VROOM |
| Study hypothesis | A two-week temporary suspension in weekly low-dose methotrexate treatment after SARS-CoV-2 vaccine boosters will improve the anti-spike-receptor binding domain (RBD) response. Mechanistic sub-study (in a subset of 100 participants): The neutralising antibody response will correlate with the anti-spike-RBD antibody in this immune-suppressed population as in other healthy populations. |
| Ethics approval(s) | Approved 20/08/2021, Yorkshire & The Humber - Leeds West Research Ethics Committee (Meeting held by video-conference via Zoom; +44 (0)207 972 2504, +44 (0)207 104 8088; leedswest.rec@hra.nhs.uk), ref: 21/YH/0209 |
| Condition | Inflammatory polyarthropathies, rheumatoid arthritis, psoriasis, seronegative spondyloarthritis, reactive arthritis, atopic eczema, polymyalgia rheumatica, systemic lupus erythematosus |
| Intervention | Participants will be randomised into the two arms (experimental intervention or control intervention) in a 1:1 ratio using the minimisation factors: 1. Inflammatory condition type (inflammatory rheumatic disease (+/- skin disease), skin disease alone) 2. Age group (<40 years, 40-64 years, ≥65 years) 3. Previous vaccination platform received (mRNA, vector, combination) Allocation will occur using a bespoke randomisation system developed and validated within the Oxford Clinical Trials Research Unit (OCTRU) at the University of Oxford. Participants will enter their age group, inflammatory condition grouping, and which 2 COVID vaccinations were received previously into the randomisation system. Experimental intervention: To suspend methotrexate for two weeks immediately after receiving the SARS-CoV-2 booster vaccination. Control intervention: To continue on the same dose of methotrexate as usual after SARS-CoV-2 booster vaccination. |
| Intervention type | Drug |
| Pharmaceutical study type(s) | |
| Phase | Phase III/IV |
| Drug / device / biological / vaccine name(s) | Methotrexate |
| Primary outcome measure | Anti-spike receptor binding domain (RBD) antibody level measured from blood sample collected at 4 weeks post SARS-CoV-2 booster vaccination |
| Secondary outcome measures | 1. Level of anti-spike RBD antibody measured from blood sample collected at 12 weeks post booster vaccination 2. Patient assessments of disease activity measured using: 2.1. Global assessment using a numeric rating scale with one-week recall at baseline, 2, 4, and 12 weeks post booster vaccination 2.2. Current disease activity level and change since booster, 4 and 12 weeks post booster vaccination 3. Disease flare-up and actions taken to deal with them measured using patient self-report at 4 and 12 weeks post booster vaccination 4. Effect on quality of life measured using the EQ-5D-5L questionnaire at 4 and 12 weeks post booster vaccination 5. Adherence with advice to interrupt or continue methotrexate measured using patient self-report at 2 and 4 weeks post booster vaccination Mechanistic sub-study only: 1. COVID-19 neutralising titre measured from blood sample collected at 4 and 12 weeks post booster vaccination 2. Adherence to methotrexate allocation measured using patient self-report at 4 and 12 weeks post booster vaccination |
| Overall study start date | 01/07/2021 |
| Overall study end date | 26/09/2022 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | Both |
| Target number of participants | 560 |
| Total final enrolment | 383 |
| Participant inclusion criteria | 1. Aged ≥18 years 2. Diagnosed with inflammatory conditions such as rheumatoid arthritis, psoriasis with or without arthritis, seronegative spondyloarthritis, reactive arthritis, atopic eczema, polymyalgia rheumatica, or systemic lupus erythematosus. This is not an exhaustive list and people with other inflammatory conditions where treatment may be interrupted for two weeks without the risk of a substantial increase in disease activity, or organ or life-threatening flare up will also be eligible to participate in the study in order to increase the generalisability of the study. 3. Prescribed with oral or subcutaneous methotrexate (≤25 mg/week) +/- hydroxychloroquine weekly administered for at least the previous three months 4. Able to temporarily suspend methotrexate for two weeks in the opinion of patients’ consultant without the risk of substantial increase in disease activity, or organ or life-threatening flare-up 5. Able to give informed consent; 6. Eligible for planned booster vaccination for COVID-19 (i.e. have received any 2 vaccinations from the original NHS COVID Vaccination Programme 2020/21) |
| Participant exclusion criteria | Current participant exclusion criteria as of 08/03/2022: 1. Diagnosed with any of: ANCA associated vasculitis, large vessel vasculitis, myositis, giant cell arteritis, solid organ transplant or any another inflammatory condition for which treatment cannot be interrupted safely. 2. Treated with Rituximab drip in the last 18 months or planning to start it 3. Concurrent immune suppressive treatments in the last two months specifically leflunomide, ciclosporin, azathioprine or mercaptopurine, sulfasalazine or other 5-amino-salicylic acid drugs, mycophenolate, apremilast, or biologic agents 4. Radiotherapy or cancer chemotherapy in last six months 5. Prednisolone dose >7.5 mg/day within 30 days of randomisation 6. Active solid organ cancer (people with skin cancer or those cured of solid organ cancer are eligible) Previous participant exclusion criteria: 1. Diagnosed with inflammatory conditions for which treatment cannot be interrupted safely such as ANCA associated vasculitis, large vessel vasculitis, myositis, giant cell arteritis, or solid organ transplant 2. Treated with Rituximab drip in the last 18 months or planning to start it 3. Concurrent immune suppressive treatments in the last two months specifically leflunomide, ciclosporin, azathioprine or mercaptopurine, sulfasalazine or other 5-amino-salicylic acid drugs, mycophenolate, apremilast, or biologic agents 4. Radiotherapy or cancer chemotherapy in last six months 5. Prednisolone dose >7.5 mg/day within 30 days of randomisation 6. Active solid organ cancer (people with skin cancer or those cured of solid organ cancer are eligible) |
| Recruitment start date | 30/09/2021 |
| Recruitment end date | 07/03/2022 |
Locations
Countries of recruitment
- England
- United Kingdom
- Wales
Study participating centres
Queens Medical Centre
Derby Road
Nottingham
NG7 2UH
United Kingdom
Mansfield Road
Sutton-in-ashfield
NG17 4JL
United Kingdom
Cannock Chase Hospital
Brunswick Road
Cannock
Staffordshire
WS11 5XY
United Kingdom
Marlborough Road
Swindon
SN3 6BB
United Kingdom
Cardiff Road
Newport
NP20 2EF
United Kingdom
Calow
Chesterfield
S44 5BL
United Kingdom
Ansari Court
CF72 8TB
United Kingdom
Sheriff Hill
Gateshead
NE9 6SX
United Kingdom
Lancaster Park Road
Harrogate
HG2 7SX
United Kingdom
Du Cane Road
London
W12 0HS
United Kingdom
Vicarage Lane
Preston
PR2 8DW
United Kingdom
High Lane
Stoke on Trent
ST6 7AG
United Kingdom
Colney
Norwich
NR4 7UY
United Kingdom
The Cumberland Infirmary
Port Road
Carlisle
CA2 7AF
United Kingdom
Bretton Gate
Bretton
Peterborough
PE3 9GZ
United Kingdom
Windmill Road
Oxford
OX3 7LD
United Kingdom
Pensnett Road
Dudley
DY1 2HQ
United Kingdom
Freeman Road
High Heaton
Newcastle upon Tyne
NE7 7DN
United Kingdom
King's Lynn
PE30 4ET
United Kingdom
Oswestry
SY10 7AG
United Kingdom
Newton Road
Torquay
TQ2 7AA
United Kingdom
Tremona Road
Southampton
SO16 6YD
United Kingdom
Clifford Bridge Road
Coventry
CV2 2DX
United Kingdom
Abbey Road
Brigton
BN2 1ES
United Kingdom
Arrowe Park Road
Upton
Wirral
CH49 5PE
United Kingdom
Wigginton Road
York
YO31 8HE
United Kingdom
Sponsor information
University/education
Research and Innovation, University of Nottingham
East Atrium, Jubilee Conference Centre
Triumph Road
Nottingham
NG8 1DH
England
United Kingdom
| Phone | +44 (0)1158467906 |
|---|---|
| sponsor@nottingham.ac.uk | |
| Website | http://www.nottingham.ac.uk/ |
"ROR" |
https://ror.org/01ee9ar58 |
Funders
Funder type
Government
Government organisation / National government
- Alternative name(s)
- NIHR Efficacy and Mechanism Evaluation Programme, EME
- Location
- United Kingdom
Results and Publications
| Intention to publish date | 01/10/2023 |
|---|---|
| Individual participant data (IPD) Intention to share | Yes |
| IPD sharing plan summary | Available on request |
| Publication and dissemination plan | The study will be publicised to research, clinical and patient communities and other important stakeholders, such as self-help groups. Once the study is completed, in addition to the final report for the NIHR EME Programme, we aim to publish the study results in peer-reviewed high impact journals such as the BMJ or the Lancet and present at national and international meetings to ensure maximum impact and rapid dissemination. Additionally, we will seek to disseminate findings through publication in other journals, such as Pulse, newsletters to British Society for Rheumatology, British Association of Dermatology, and Royal College of General Practitioners. We will engage with patients; primary care clinicians; Royal College of General Practitioners. We will ensure that the study results are disseminated to the guideline writing groups. |
| IPD sharing plan | Participant level dataset and statistical code will be made available upon reasonable request to OCTRU and the CI, once the VROOM study findings have been published in full. Some specific data items may not be shared in order to maintain participant anonymity. |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Protocol article | 03/05/2022 | 04/05/2022 | Yes | No | |
| Results article | 27/06/2022 | 01/07/2022 | Yes | No | |
| HRA research summary | 28/06/2023 | No | No | ||
| Results article | 12/12/2023 | 25/01/2024 | Yes | No |
Editorial Notes
25/01/2024: Publication reference added.
09/08/2023: The following changes were made to the study record:
1. The overall study end date was changed from 31/08/2023 to 26/09/2022 and the plain English summary updated accordingly.
2. The intention to publish date was changed from 01/09/2023 to 01/10/2023.
3. The public contact was changed.
08/06/2023: The following changes were made to the study record:
1. The recruitment start date was changed from 01/09/2021 to 30/09/2021.
2. The recruitment end date was changed from 31/08/2022 to 07/03/2022.
01/07/2022: Publication reference added.
04/05/2022: Publication reference added.
09/03/2022: Internal review.
08/03/2022: The following changes have been made:
1. The total final enrolment number has been added.
2. The participant exclusion criteria have been updated.
3. The individual participant data (IPD) sharing statement has been added and the IPD sharing summary has been changed from "Data sharing statement to be made available at a later date" to "Available on request".
4. The trial participating centres "Aneurin Bevan University Health Board”, “Chesterfield Royal Hospital NHS Foundation Trust”, “Cwm Taf Morgannwg University Health Board”, “Gateshead Health NHS Foundation Trust”, “Harrogate and District NHS Foundation Trust”, “Imperial College Healthcare NHS Trust”, “Lancashire & South Cumbria NHS Foundation Trust”, “Midlands Partnership NHS Foundation Trust”, “Norfolk and Norwich University Hospitals NHS Foundation Trust”, “North Cumbria Integrated Care NHS Foundation Trust”, “North West Anglia NHS Foundation Trust”, “Oxford University Hospitals NHS Foundation Trust”, “The Dudley Group NHS Foundation Trust”, “The Newcastle Upon Tyne Hospitals NHS Foundation Trust”, “The Queen Elizabeth Hospital, King's Lynn. NHS Foundation Trust”, “The Robert Jones and Agnes Hunt Orthopaedic Hospital NHS Foundation Trust”, “Torbay and South Devon NHS Foundation Trust”, “University Hospital Southampton NHS Foundation Trust”, “University Hospitals Coventry and Warwickshire NHS Trust”, “University Hospitals Sussex NHS Foundation Trust”, “Wirral University Teaching Hospital NHS Foundation Trust”, and “York and Scarborough Teaching Hospitals NHS Foundation Trust" have been added.
01/10/2021: The following changes have been made:
1. The ethics approval has been added.
2. The trial participating centres "Sherwood Forest Hospitals NHS Foundation Trust", "Royal Wolverhampton NHS Trust", and "Great Western Hospitals NHS Foundation Trust" have been added.
23/07/2021: Trial’s existence confirmed by the National Institute for Health Research (NIHR).
