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

Sponsor:	Sanjay Gandhi Postgraduate Institute of Medical Sciences
Information provided by:	Sanjay Gandhi Postgraduate Institute of Medical Sciences
ClinicalTrials.gov Identifier:	NCT01040195

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 III

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:

Genetics Home Reference related topics: ankylosing spondylitis

MedlinePlus related topics: Ankylosing Spondylitis Back Pain

Drug Information available for: Methotrexate Hydroxychloroquine Sulfasalazine Hydroxychloroquine sulfate

U.S. FDA Resources

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 ]

Estimated Enrollment:	100
Study Start Date:	June 2009
Estimated Study Completion Date:	December 2012
Estimated Primary Completion Date:	March 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

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

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

Contacts

Contact: Vikas Agarwal, MD, DM	91-522-2494318	vikasagr@yahoo.com
Contact: Vishad Viswanath, MD	91-9919642573	vishadv@gmail.com

Locations

India
Sanjay Gandhi Postgraduate Institute of Medical Sciences	Recruiting
Lucknow, UP, India, 226014
Contact: Vikas Agarwal, MD, DM 91-522-2494318 vikasagr@yahoo.com
Principal Investigator: Vikas Agarwal, MD, DM

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, Assistant professor, SGPGIMS
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:	April 11, 2011
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
Enzyme Inhibitors

Molecular Mechanisms of Pharmacological Action
Antimalarials
Antiprotozoal Agents
Antiparasitic Agents
Anti-Infective Agents
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 February 09, 2012