- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01040195
Combination Disease-Modifying Antirheumatic Drugs (DMARDs) Versus Sulfasalazine in Inflammatory Back Pain
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
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.
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Study Type
Enrollment (Actual)
Phase
- Phase 3
Contacts and Locations
Study Locations
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UP
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Lucknow, UP, India, 226014
- Sanjay Gandhi Postgraduate Institute of Medical Sciences
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Patients who fulfilled criteria for the diagnosis of Ankylosing Spondylitis (Modified New York Criteria) or undifferentiated spondyloarthropathy (UspA) (Amor criteria) and are within 8 years of disease onset with:
- Inflammatory back Pain of more than 6 months
- BASDAI ≥4 or EMS ≥45 minutes
- Have failed maximum dose of at least one NSAID for 6 weeks.
Exclusion Criteria:
- Patients with renal diseases
- patients with hepatic diseases
- Patients with severe uncorrected anemia (Hb<7gm)
- Patients previously received full dose of sulfasalazine and/or methotrexate with inadequate relief
- Pregnant or lactating females
- Malignancy or active infection
- Patient requiring and affording biologicals
- Patients who have received steroids in the past 3 months
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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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.
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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.
Other Names:
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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.
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Identical placebos (for methotrexate and hydroxychloroquine)will be prepared and prescribed in identical fashion as the methotrexate and hydroxychloroquine in the combination DMARD arm.
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Primary end point will be number of patients attaining Assessment of spondyloarthropathy international society 20 (ASAS20) response.
Time Frame: 28 weeks
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28 weeks
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Secondary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Improvement in Bath ankylosing spondylitis disease activity index (BASDAI)
Time Frame: 28 weeks
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28 weeks
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Improvement in Bath ankylosing spondylitis functional index (BASFI)
Time Frame: 28 weeks
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28 weeks
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Improvement in Bath ankylosing spondylitis metrology index (BASMI)
Time Frame: 28 weeks
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28 weeks
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Improvement in Maastricht Ankylosing Spondylitis Enthesitis Index
Time Frame: 28 weeks
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28 weeks
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Patient pain and global assessment of disease
Time Frame: 28 weeks
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28 weeks
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Physician assessment of pain and global disease
Time Frame: 28 weeks
|
28 weeks
|
change in Short form 36 (SF-36) and health assessment questionnaire (HAQ) parameters
Time Frame: 28 weeks
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28 weeks
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improvement in erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP)
Time Frame: 28 weeks
|
28 weeks
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Reduction in non steroidal anti-inflammatory drug (NSAID) dose
Time Frame: 28 weeks
|
28 weeks
|
Collaborators and Investigators
Investigators
- Principal Investigator: Vikas Agarwal, MD, DM, SGPGIMS
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Infections
- Joint Diseases
- Musculoskeletal Diseases
- Arthritis
- Spinal Diseases
- Bone Diseases
- Bone Diseases, Infectious
- Spondylitis
- Spondylarthritis
- Spondylarthropathies
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Anti-Infective Agents
- Nucleic Acid Synthesis Inhibitors
- Enzyme Inhibitors
- Antirheumatic Agents
- Antimetabolites, Antineoplastic
- Antimetabolites
- Antineoplastic Agents
- Immunosuppressive Agents
- Immunologic Factors
- Dermatologic Agents
- Reproductive Control Agents
- Antiprotozoal Agents
- Antiparasitic Agents
- Antimalarials
- Abortifacient Agents, Nonsteroidal
- Abortifacient Agents
- Folic Acid Antagonists
- Methotrexate
- Hydroxychloroquine
Other Study ID Numbers
- A-08:PGI/DM/IEC/45/7.2.2009
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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