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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Vikas Agarwal, Sanjay Gandhi Postgraduate Institute of Medical Sciences
ClinicalTrials.gov Identifier:
NCT01040195
First received: December 25, 2009
Last updated: March 21, 2013
Last verified: March 2013

December 25, 2009
March 21, 2013
June 2009
November 2012   (final data collection date for primary outcome measure)
Primary end point will be number of patients attaining Assessment of spondyloarthropathy international society 20 (ASAS20) response. [ Time Frame: 28 weeks ] [ Designated as safety issue: No ]
Same as current
Complete list of historical versions of study NCT01040195 on ClinicalTrials.gov Archive Site
  • Improvement in Bath ankylosing spondylitis disease activity index (BASDAI) [ Time Frame: 28 weeks ] [ Designated as safety issue: No ]
  • Improvement in Bath ankylosing spondylitis functional index (BASFI) [ Time Frame: 28 weeks ] [ Designated as safety issue: No ]
  • Improvement in Bath ankylosing spondylitis metrology index (BASMI) [ Time Frame: 28 weeks ] [ Designated as safety issue: No ]
  • Improvement in Maastricht Ankylosing Spondylitis Enthesitis Index [ Time Frame: 28 weeks ] [ Designated as safety issue: No ]
  • Patient pain and global assessment of disease [ Time Frame: 28 weeks ] [ Designated as safety issue: No ]
  • Physician assessment of pain and global disease [ Time Frame: 28 weeks ] [ Designated as safety issue: No ]
  • change in Short form 36 (SF-36) and health assessment questionnaire (HAQ) parameters [ Time Frame: 28 weeks ] [ Designated as safety issue: No ]
  • improvement in erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) [ Time Frame: 28 weeks ] [ Designated as safety issue: No ]
  • Reduction in non steroidal anti-inflammatory drug (NSAID) dose [ Time Frame: 28 weeks ] [ Designated as safety issue: No ]
Same as current
Not Provided
Not Provided
 
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.

Spondyloarthropathies SpA

Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Seronegative Spondyloarthropathies
  • 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
  • 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.
    Other Name: placebo
  • 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.
    Intervention: Drug: Methotrexate, Hydroxychloroquine
  • 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.
    Intervention: Drug: Placebo
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
33
December 2012
November 2012   (final data collection date for primary outcome measure)

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
Both
18 Years to 60 Years
No
Contact information is only displayed when the study is recruiting subjects
India
 
NCT01040195
A-08:PGI/DM/IEC/45/7.2.2009
Yes
Vikas Agarwal, Sanjay Gandhi Postgraduate Institute of Medical Sciences
Sanjay Gandhi Postgraduate Institute of Medical Sciences
Not Provided
Principal Investigator: Vikas Agarwal, MD, DM SGPGIMS
Sanjay Gandhi Postgraduate Institute of Medical Sciences
March 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP