Combination Disease-Modifying Antirheumatic Drugs (DMARDs) Versus Sulfasalazine in Inflammatory Back Pain
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|ClinicalTrials.gov Identifier: NCT01040195|
Recruitment Status : Completed
First Posted : December 29, 2009
Last Update Posted : March 22, 2013
Till now no drug has been conclusively shown to affect the natural course of the inflammatory back ache in seronegative spondylarthropathies. Non-steroidal anti-inflammatory drugs (NSAIDS) have been the main stay of treatment for these diseases for long. Despite providing good pain relief, they are largely ineffective in altering the natural course of these diseases. However, very often, in spite of therapy, pain and discomfort continues in these patients with recurrent exacerbations. Other drugs have been tried in these patients.
The DMARDS (Disease Modifying Anti Rheumatic Drugs) are a group of drugs which have come into prominence following their remarkable efficacy in the management of Rheumatoid Arthritis, another chronic inflammatory autoimmune arthritis. The major drugs which come in this group are Methotrexate, Sulfasalazine, Hydroxychloroquine and Leflunomide. Of these drugs, the most well studied drug in Spondylarthropathy is Sulfasalazine. Trials have shown variable results of response of spondyloarthropathy to sulfasalazine. The other major DMARD tried is methotrexate. Though large well controlled trials are lacking, the available data on its efficacy in spondyloarthropathy has not been favorable. Leflunomide, the other major DMARD has also fared poorly in a controlled trial in ankylosing spondylitis. There is at present inadequate data regarding the efficacy of Hydroxychloroquine.
The discovery of anti TNF-α have been the major breakthrough in the management of ankylosing spondylitis (AS) and Spondyloarthropathies (SpA). These drugs, besides providing symptomatic improvement, also produce improvement in the indices of disease activity as Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and the Assessment of Spondylo-Arthritis International Society (ASAS). Besides, the enormous cost, incurred at a rate of about Rs 700,000/- per annum, put it out of reach of the majority of affected population. Add to these is the increased risk of tuberculosis and fungal infections, a major problem in India.
In this background there is severe and pressing need for alternate safe and effective drugs in the management of these diseases. It is here that the combination DMARD therapy assumes importance as a potential safe and cheaper alternative.
We aim to assess the efficacy of combination DMARD therapy in patients with early inflammatory chronic backache in patients with sero negative spondyloarthropathies.
|Condition or disease||Intervention/treatment||Phase|
|Seronegative Spondyloarthropathies||Drug: Methotrexate, Hydroxychloroquine Drug: Placebo||Phase 3|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||33 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
|Official Title:||A Prospective Double Blind Placebo Controlled Trial of Combination Disease Modifying Antirheumatic Drugs (DMARDs) vs Monotherapy (Sulfasalazine) in Patients With Inflammatory Low Backache in Early Seronegative Spondylarthropathy|
|Study Start Date :||June 2009|
|Actual Primary Completion Date :||November 2012|
|Actual Study Completion Date :||December 2012|
Active Comparator: Combination DMARD
All patients included in the study, will be started on Sulfasalazine 1 gm once daily and in the absence of side effects increased to 2gm daily. All patients will also receive folic acid 5 mg thrice weekly. At the end of four weeks the patients will be reassessed with baseline hemogram, SGPT, SGOT and serum Creatinine. In the absence of any contraindication, patients will be randomized into two groups Group 1 to receive Combination Disease Modifying therapy with Sulfasalazine, Methotrexate and hydroxychloroquine (HCQ). Patient will be started on Methotrexate/placebo at 10 mg once weekly and increased every week by 2.5 mg to maximum dose of 20 mg per week in the absence of side effects. These patients will also be started on Hydroxychloroquine 200 mg per day.
Drug: Methotrexate, Hydroxychloroquine
Methotrexate will be prepared as unmarked tablets of 2.5 mg strength each and Hydroxychloroquine as unmarked tablet of 200 mg strength. Patients will be started on Methotrexate/placebo at 10 mg once weekly and increased every week by 2.5 mg to maximum dose of 20 mg per week in the absence of side effects. These patients will also be started on Hydroxychloroquine 200 mg per day or placebo.
Placebo Comparator: Placebo
All patients included in the study, will be started on Sulfasalazine 1 gm once daily and in the absence of side effects increased to 2gm daily All patients will also receive folic acid 5 mg twice weekly. At the end of four weeks the patients will be reassessed with baseline hemogram, SGPT, SGOT and serum Creatinine. Group 2 patients will receive Sulfasalazine and placebo for methotrexate and hydroxychloroquine.
Identical placebos (for methotrexate and hydroxychloroquine)will be prepared and prescribed in identical fashion as the methotrexate and hydroxychloroquine in the combination DMARD arm.
- Primary end point will be number of patients attaining Assessment of spondyloarthropathy international society 20 (ASAS20) response. [ Time Frame: 28 weeks ]
- Improvement in Bath ankylosing spondylitis disease activity index (BASDAI) [ Time Frame: 28 weeks ]
- Improvement in Bath ankylosing spondylitis functional index (BASFI) [ Time Frame: 28 weeks ]
- Improvement in Bath ankylosing spondylitis metrology index (BASMI) [ Time Frame: 28 weeks ]
- Improvement in Maastricht Ankylosing Spondylitis Enthesitis Index [ Time Frame: 28 weeks ]
- Patient pain and global assessment of disease [ Time Frame: 28 weeks ]
- Physician assessment of pain and global disease [ Time Frame: 28 weeks ]
- change in Short form 36 (SF-36) and health assessment questionnaire (HAQ) parameters [ Time Frame: 28 weeks ]
- improvement in erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) [ Time Frame: 28 weeks ]
- Reduction in non steroidal anti-inflammatory drug (NSAID) dose [ Time Frame: 28 weeks ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01040195
|Sanjay Gandhi Postgraduate Institute of Medical Sciences|
|Lucknow, UP, India, 226014|
|Principal Investigator:||Vikas Agarwal, MD, DM||SGPGIMS|