SWITCH Clinical Trial for Patients With Rheumatoid Arthritis Who Have Failed an Initial TNF-blocking Drug.
NCT ID: NCT01295151
Last Updated: 2016-11-02
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.
COMPLETED
PHASE4
122 participants
INTERVENTIONAL
2011-08-31
2015-11-30
Brief Summary
Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.
Detailed Description
Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.
Conditions
See the medical conditions and disease areas that this research is targeting or investigating.
Study Design
Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.
RANDOMIZED
PARALLEL
TREATMENT
NONE
Study Groups
Review each arm or cohort in the study, along with the interventions and objectives associated with them.
TNF-blocking drug
Etanercept
Etanercept will be administered at a dose of 50mg by subcutaneous injection per week for a total of 12 weeks. Further treatment will be prescribed at the discretion of the treating clinician.
The patient will be taught how to administer the subcutaneous injection and injections will be monitored by the hospital until the patient is proficient with the technique.
Adalimumab
Adalimumab will be given at a dose of 40mg by subcutaneous injection every two weeks for a minimum of 12 weeks. Further treatment will be prescribed at the discretion of the treating clinician.
The patient will be taught how to administer the subcutaneous injection and injections will be monitored by the hospital until the patient is proficient with the technique.
Certolizumab Pegol
Certolizumab Pegol will be given at a dose of 400mg by subcutaneous injection at weeks 0, 2, 4and then at a dose of 200mg every two weeks thereafter for a minimum of 12 weeks. Further treatment will be prescribed at the discretion of the treating clinician.
The patient will be taught how to administer the subcutaneous injection and injections will be monitored by the hospital until the patient is proficient with the technique.
Infliximab
Infliximab will be given at a dose of 3mg/kg per intravenous infusion in clinic.
The intravenous infusions will be administered at week 0, 2, 6 and then 8-weekly thereafter for a minimum of 12 weeks.
Further treatment will be prescribed at the discretion of the treating clinician.
Golimumab
Golimumab will be given at a dose of 50mg by subcutaneous injection every 4 weeks for a minimum of 24 weeks.
Further treatment will be prescribed in line with the study protocol and following week 48, at the discretion of the treating clinician.
The participant will be taught how to administer the subcutaneous injection and injections will be monitored according to local arrangements until the participant is proficient with the technique according to local practice.
Abatacept
Abatacept
Abatacept will be administered at a dose determined by body weight:
Body Weight (kg) Dose (mg) \< 60kg = 500 mg
\> or equal to 60kg and \< or equal to 100kg = 750 mg \> 100 kg = 1000mg
The intravenous infusions will be administered in clinic on days 1, 15, 29 and every 28 days thereafter for a minimum of 24 weeks. Further treatment will be prescribed at the discretion of the treating clinician.
Rituximab
Rituximab
Rituximab will be given at a dose of 1000mg; 2 intravenous infusions will be administered at days 0 (week 0) and 15 (week 2).
In line with standard practice, a patient who loses an initial response with a DAS28 increase of at least 0.6 may receive a further cycle of rituximab at the discretion of the treating clinician.
Prior to receiving rituximab, intravenous methylprednisolone 100mg will also be given.
Interventions
Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.
Etanercept
Etanercept will be administered at a dose of 50mg by subcutaneous injection per week for a total of 12 weeks. Further treatment will be prescribed at the discretion of the treating clinician.
The patient will be taught how to administer the subcutaneous injection and injections will be monitored by the hospital until the patient is proficient with the technique.
Abatacept
Abatacept will be administered at a dose determined by body weight:
Body Weight (kg) Dose (mg) \< 60kg = 500 mg
\> or equal to 60kg and \< or equal to 100kg = 750 mg \> 100 kg = 1000mg
The intravenous infusions will be administered in clinic on days 1, 15, 29 and every 28 days thereafter for a minimum of 24 weeks. Further treatment will be prescribed at the discretion of the treating clinician.
Rituximab
Rituximab will be given at a dose of 1000mg; 2 intravenous infusions will be administered at days 0 (week 0) and 15 (week 2).
In line with standard practice, a patient who loses an initial response with a DAS28 increase of at least 0.6 may receive a further cycle of rituximab at the discretion of the treating clinician.
Prior to receiving rituximab, intravenous methylprednisolone 100mg will also be given.
Adalimumab
Adalimumab will be given at a dose of 40mg by subcutaneous injection every two weeks for a minimum of 12 weeks. Further treatment will be prescribed at the discretion of the treating clinician.
The patient will be taught how to administer the subcutaneous injection and injections will be monitored by the hospital until the patient is proficient with the technique.
Certolizumab Pegol
Certolizumab Pegol will be given at a dose of 400mg by subcutaneous injection at weeks 0, 2, 4and then at a dose of 200mg every two weeks thereafter for a minimum of 12 weeks. Further treatment will be prescribed at the discretion of the treating clinician.
The patient will be taught how to administer the subcutaneous injection and injections will be monitored by the hospital until the patient is proficient with the technique.
Infliximab
Infliximab will be given at a dose of 3mg/kg per intravenous infusion in clinic.
The intravenous infusions will be administered at week 0, 2, 6 and then 8-weekly thereafter for a minimum of 12 weeks.
Further treatment will be prescribed at the discretion of the treating clinician.
Golimumab
Golimumab will be given at a dose of 50mg by subcutaneous injection every 4 weeks for a minimum of 24 weeks.
Further treatment will be prescribed in line with the study protocol and following week 48, at the discretion of the treating clinician.
The participant will be taught how to administer the subcutaneous injection and injections will be monitored according to local arrangements until the participant is proficient with the technique according to local practice.
Eligibility Criteria
Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.
Inclusion Criteria
2. Patients with a diagnosis of rheumatoid arthritis as per the ACR/EULAR 2010 classification criteria (Appendix 7) confirmed at least 24 weeks prior to the screening visit.
3. Patients who have failed conventional DMARD therapy as per NICE/BSR Guidelines (49) i.e. failure of at least 2 DMARDS including MTX.
4. Patients with persistent RA disease activity despite having been treated with a current initial TNFi agent for at least 12 weeks. Active RA defined as\*:
1. Primary non-response: failing to improve DAS28 by \> 1.2 (Appendix 6) or failing to achieve DAS28 ≤ 3.2 within the first 12 to 24 weeks of starting the initial TNFi.
• This may include patients that have shown a reduction in DAS28 of \> 1.2 but still demonstrate unacceptably high disease activity in the physician's judgement with evidence of an overall DAS28 of ≥ 3.2 OR
2. Secondary non-response: defined as inefficacy to first TNFi (having demonstrated prior satisfactory response) as per clinician judgement; with intolerance not the reason for cessation of first TNFi.
5. MTX dose stable for 4 weeks prior to the screening visit and to be continued for the duration of the study.
6. Patients on NSAIDs and / or corticosteroids (oral prednisolone not exceeding 10mg daily) who have been on an unchanged regimen for at least 4 weeks prior to the screening visit and are expected to remain on a stable dose until the baseline assessments have been completed.
7. Provided written informed consent prior to any trial-specific procedures.
Exclusion Criteria
2. Patients with inflammatory joint disease of different origin, mixed connective tissue disease, Reiter's syndrome, psoriatic arthritis, systemic lupus erythematosus, or any arthritis with onset prior to 16 years of age.
3. Patients receiving doses of prednisolone \> 10mg/day within the 4 weeks prior to the screening visit.
4. Patients receiving intra-articular or intra-muscular steroid injections within 4 weeks prior to the screening visit.
5. Patients who have previously received more than 1 TNFi drug OR any other biological therapy for the treatment of RA.
6. Patients unable or unwilling to stop treatment with a prohibited DMARD (i.e synthetic DMARD aside from MTX e.g. oral or injectable gold, chloroquine, hydroxychloroquine, cyclosporine, azathioprine, leflunomide, sulphasalazine) prior to the start of protocol treatment.
7. Treatment with any investigational drug in the last 12 weeks prior the start of protocol treatment.
8. Patients with other co-morbidity including acute, severe infections, uncontrolled diabetes, uncontrolled hypertension, unstable ischaemic heart disease, moderate/severe heart failure (Class III/IV of the New York Heart Association (NYHA) functional classification system (79)), active bowel disease, active peptic ulcer disease, recent stroke (within 12 weeks before the screening visit), or any other condition which, in the opinion of the investigator, would put the patient at risk to participate in the study or would make implementation of the protocol difficult.
9. Patients with any major episode of infection requiring hospitalisation or treatment with IV antibiotics within 12 weeks of start of treatment protocol or oral antibiotics within 4 weeks of start of protocol treatment.
10. Patients at significant risk of infection, which in the opinion of the investigator would put the patient at risk to participate in the study (e.g. leg ulceration, indwelling urinary catheter, septic joint within 52 weeks (or ever if prosthetic joint still in situ)).
11. Patients with known active current or history of recurrent bacterial, viral, fungal, mycobacterial or other infections including herpes zoster (for tuberculosis and Hepatitis B and C see below), but excluding fungal infections of nail beds as per clinical judgment.
12. Patients with untreated active current or latent tuberculosis (TB). Patients should have been screened for latent TB (as per BSR guidelines) within 24 weeks prior to the screening visit and, if positive, treated following local practice guidelines prior to the start of protocol treatment.
13. Patients with active current hepatitis B and/or C infection. Patients should have been screened for hepatitis B and C within 24 weeks prior to the screening visit and if positive, excluded from the study.
14. Primary or secondary immunodeficiency (history of or currently active) unless related to primary disease under investigation.
15. Pregnancy, lactation or women of child-bearing potential (WCBP) unwilling to use an effective birth control measure (Appendix 2) whilst receiving treatment and after the last dose of protocol treatment as indicated in the relevant SmPC/IB.
16. Men whose partners are of child-bearing potential but who are unwilling to use an effective birth control measure (Appendix 2) whilst receiving treatment and after the last dose of protocol treatment as indicated in the relevant SmPC/IB.
17. Patients with known significantly impaired bone marrow function as for example significant anaemia, leukopaenia, neutropaenia or thrombocytopaenia as shown by the following laboratory values at the time of the screening visit:
* Haemoglobin \< 8.5 g/dl
* Platelet count \< 100 x 109 / L
* White blood cell count \< 2.0 x 109 / L
* Neutrophil count \< 1 x 109 / L
18. Patients with known severe hypoproteinaemia at the time of the screening visit, e.g. in nephrotic syndrome or impaired renal function, as shown by:
* Serum Creatinine \> 150 umol / L
18 Years
ALL
No
Sponsors
Meet the organizations funding or collaborating on the study and learn about their roles.
Julia Brown
OTHER
Responsible Party
Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.
Julia Brown
Director of Leeds Institute of Clinical Trials Research
Principal Investigators
Learn about the lead researchers overseeing the trial and their institutional affiliations.
Maya Buch
Role: PRINCIPAL_INVESTIGATOR
University of Leeds
Locations
Explore where the study is taking place and check the recruitment status at each participating site.
Institute of Rheumatic & Musculoskeletal Medicine, Chapel Allerton Hospital
Leeds, West Yorkshire, United Kingdom
Countries
Review the countries where the study has at least one active or historical site.
References
Explore related publications, articles, or registry entries linked to this study.
Plein S, Erhayiem B, Fent G, Horton S, Dumitru RB, Andrews J, Greenwood JP, Emery P, Hensor EM, Baxter P, Pavitt S, Buch MH. Cardiovascular effects of biological versus conventional synthetic disease-modifying antirheumatic drug therapy in treatment-naive, early rheumatoid arthritis. Ann Rheum Dis. 2020 Nov;79(11):1414-1422. doi: 10.1136/annrheumdis-2020-217653. Epub 2020 Aug 28.
Brown S, Everett CC, Naraghi K, Davies C, Dawkins B, Hulme C, McCabe C, Pavitt S, Emery P, Sharples L, Buch MH. Alternative tumour necrosis factor inhibitors (TNFi) or abatacept or rituximab following failure of initial TNFi in rheumatoid arthritis: the SWITCH RCT. Health Technol Assess. 2018 Jun;22(34):1-280. doi: 10.3310/hta22340.
Navarro Coy NC, Brown S, Bosworth A, Davies CT, Emery P, Everett CC, Fernandez C, Gray JC, Hartley S, Hulme C, Keenan AM, McCabe C, Redmond A, Reynolds C, Scott D, Sharples LD, Pavitt S, Buch MH. The 'Switch' study protocol: a randomised-controlled trial of switching to an alternative tumour-necrosis factor (TNF)-inhibitor drug or abatacept or rituximab in patients with rheumatoid arthritis who have failed an initial TNF-inhibitor drug. BMC Musculoskelet Disord. 2014 Dec 23;15:452. doi: 10.1186/1471-2474-15-452.
Other Identifiers
Review additional registry numbers or institutional identifiers associated with this trial.
2010-023880-17
Identifier Type: EUDRACT_NUMBER
Identifier Source: secondary_id
RR10/9589
Identifier Type: -
Identifier Source: org_study_id