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
  Purpose

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 Intervention Phase
Seronegative Spondyloarthropathies
Drug: Methotrexate, Hydroxychloroquine
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, 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

Resource links provided by NLM:


Further study details as provided by Sanjay Gandhi Postgraduate Institute of Medical Sciences:

Primary Outcome Measures:
  • 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 ]

Secondary Outcome Measures:
  • 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 ]

Enrollment: 33
Study Start Date: June 2009
Study Completion Date: December 2012
Primary Completion Date: November 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
Other Name: placebo

Detailed Description:

Spondyloarthropathies SpA

  Eligibility

Ages Eligible for Study:   18 Years to 60 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01040195

Locations
India
Sanjay Gandhi Postgraduate Institute of Medical Sciences
Lucknow, UP, India, 226014
Sponsors and Collaborators
Sanjay Gandhi Postgraduate Institute of Medical Sciences
Investigators
Principal Investigator: Vikas Agarwal, MD, DM SGPGIMS
  More Information

No publications provided

Responsible Party: Vikas Agarwal, Additional Professor, Sanjay Gandhi Postgraduate Institute of Medical Sciences
ClinicalTrials.gov Identifier: NCT01040195     History of Changes
Other Study ID Numbers: A-08:PGI/DM/IEC/45/7.2.2009
Study First Received: December 25, 2009
Last Updated: March 21, 2013
Health Authority: India: Institutional Review Board

Keywords provided by Sanjay Gandhi Postgraduate Institute of Medical Sciences:
ankylosing spondylitis
undifferentiated spondyloarthropathy
spondyloarthropathy
inflammatory back pain
methotrexate
sulfasalazine
hydroxychloroquine

Additional relevant MeSH terms:
Spondylarthropathies
Spondylarthritis
Spondylitis
Spinal Diseases
Bone Diseases
Musculoskeletal Diseases
Arthritis
Joint Diseases
Antirheumatic Agents
Hydroxychloroquine
Methotrexate
Sulfasalazine
Therapeutic Uses
Pharmacologic Actions
Antimalarials
Antiprotozoal Agents
Antiparasitic Agents
Anti-Infective Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Abortifacient Agents, Nonsteroidal
Abortifacient Agents
Reproductive Control Agents
Physiological Effects of Drugs
Antimetabolites, Antineoplastic
Antimetabolites
Antineoplastic Agents
Dermatologic Agents
Folic Acid Antagonists
Immunosuppressive Agents

ClinicalTrials.gov processed this record on August 19, 2014