Combination Disease-Modifying Antirheumatic Drugs (DMARDs) Versus Sulfasalazine in Inflammatory Back Pain

Sponsor

Sanjay Gandhi Postgraduate Institute of Medical Sciences (Other)

Overall Status

Completed

CT.gov ID

NCT01040195

Collaborator

(none)

Enrollment

Location

Arms

Duration (Months)

0.8

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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

Detailed Description

Spondyloarthropathies SpA

Study Design

Study Type:

Interventional

Actual Enrollment :

33 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

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 :

Jun 1, 2009

Actual Primary Completion Date :

Nov 1, 2012

Actual Study Completion Date :

Dec 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
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. Other Names: Folitrax HCQS
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.	Drug: Placebo Identical placebos (for methotrexate and hydroxychloroquine)will be prepared and prescribed in identical fashion as the methotrexate and hydroxychloroquine in the combination DMARD arm.

Arm

Intervention/Treatment

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.

Other Names:

Folitrax

HCQS

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.

Drug: Placebo

Identical placebos (for methotrexate and hydroxychloroquine)will be prepared and prescribed in identical fashion as the methotrexate and hydroxychloroquine in the combination DMARD arm.

Outcome Measures

Primary Outcome Measures

Primary end point will be number of patients attaining Assessment of spondyloarthropathy international society 20 (ASAS20) response. [28 weeks]

Secondary Outcome Measures

Improvement in Bath ankylosing spondylitis disease activity index (BASDAI) [28 weeks]
Improvement in Bath ankylosing spondylitis functional index (BASFI) [28 weeks]
Improvement in Bath ankylosing spondylitis metrology index (BASMI) [28 weeks]
Improvement in Maastricht Ankylosing Spondylitis Enthesitis Index [28 weeks]
Patient pain and global assessment of disease [28 weeks]
Physician assessment of pain and global disease [28 weeks]
change in Short form 36 (SF-36) and health assessment questionnaire (HAQ) parameters [28 weeks]
improvement in erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) [28 weeks]
Reduction in non steroidal anti-inflammatory drug (NSAID) dose [28 weeks]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 60 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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