Seronegative SpondyloarthropathiesPhase 3NCT01040195
Combination Disease-Modifying Antirheumatic Drugs (DMARDs) Versus Sulfasalazine in Inflammatory Back Pain
A Phase 3 study testing Methotrexate, Hydroxychloroquine in people with Seronegative Spondyloarthropathies, run by Sanjay Gandhi Postgraduate Institute of Medical Sciences at 1 site in India.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 60 years
- Conditions the study is for
- Seronegative Spondyloarthropathies
- What is being tested?
- Methotrexate, Hydroxychloroquine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 33 participants
- Where
- 1 siteIndia
- Study dates
- Jun 2009to Dec 2012
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 60 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- 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.
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
India1 site
Sanjay Gandhi Postgraduate Institute of Medical Sciences
Lucknow, Uttar Pradesh, 226014
About this study
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
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.
Read more
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.
Read the detailed description
Spondyloarthropathies SpA
- Conditions
- Seronegative Spondyloarthropathies
- Being tested
- Methotrexate, Hydroxychloroquine, Placebo
- Keywords
- ankylosing spondylitis, undifferentiated spondyloarthropathy, spondyloarthropathy, inflammatory back pain, methotrexate, sulfasalazine, hydroxychloroquine
- Medical subject headings
- Spondylitis, Ankylosing, Spondylarthropathies
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Methotrexate, HydroxychloroquineDrug
Also called Folitrax, HCQS
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.
PlaceboDrug
Identical placebos (for methotrexate and hydroxychloroquine)will be prepared and prescribed in identical fashion as the methotrexate and hydroxychloroquine in the combination DMARD arm.
| Study group | Role | What they receive |
|---|---|---|
| Combination DMARD | Active comparator | 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. Receives: Drug: Methotrexate, Hydroxychloroquine |
| Placebo | Placebo comparator | 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. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Primary end point will be number of patients attaining Assessment of spondyloarthropathy international society 20 (ASAS20) response.
Measured: 28 weeks
Secondary outcomes (9)
Improvement in Bath ankylosing spondylitis disease activity index (BASDAI)
Measured: 28 weeks
Improvement in Bath ankylosing spondylitis functional index (BASFI)
Measured: 28 weeks
Improvement in Bath ankylosing spondylitis metrology index (BASMI)
Measured: 28 weeks
Improvement in Maastricht Ankylosing Spondylitis Enthesitis Index
Measured: 28 weeks
Patient pain and global assessment of disease
Measured: 28 weeks
Physician assessment of pain and global disease
Measured: 28 weeks
change in Short form 36 (SF-36) and health assessment questionnaire (HAQ) parameters
Measured: 28 weeks
improvement in erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP)
Measured: 28 weeks
Reduction in non steroidal anti-inflammatory drug (NSAID) dose
Measured: 28 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Dec 2009 (estimated)
- Study startJun 2009
- Primary completionNov 2012
- Study completionDec 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Seronegative SpondyloarthropathiesStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 33 participants (actual)
Sponsor and investigators
- Lead sponsor
- Sanjay Gandhi Postgraduate Institute of Medical Sciences
- Sponsor type
- Other government
- Responsible party
- Principal investigator, Vikas Agarwal, Sanjay Gandhi Postgraduate Institute of Medical Sciences
- Investigators
- Vikas Agarwal, MD, DM, Principal investigator, SGPGIMS
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01040195
- Sponsor's protocol ID
- A-08:PGI/DM/IEC/45/7.2.2009
- Status last verified
- Mar 2013
- First submitted
- 25 Dec 2009
- Last updated
- 22 Mar 2013
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 22 Mar 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01040195
- Acronym / sponsor ID
- A-08:PGI/DM/IEC/45/7.2.2009
- Conditions
- Seronegative Spondyloarthropathies
- Keywords
- ankylosing spondylitis, undifferentiated spondyloarthropathy, spondyloarthropathy, inflammatory back pain, methotrexate, sulfasalazine, hydroxychloroquine
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 33 participants (actual)
- Lead sponsor
- Sanjay Gandhi Postgraduate Institute of Medical SciencesOther government
- Study start
- Jun 2009
- Primary completion
- Nov 2012 (actual)
- Study completion
- Dec 2012 (actual)
- First posted
- 29 Dec 2009 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Spondyloarthropathies SpA
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Combination DMARD | Active comparator | Drug: Methotrexate, HydroxychloroquineAll 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. |
| Placebo | Placebo comparator | Drug: PlaceboAll 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. |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (4 listed)
- 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.
Key exclusion criteria (8 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Methotrexate, HydroxychloroquineAlso: Folitrax, HCQSMethotrexate 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. | Drug | Combination DMARD |
| PlaceboIdentical placebos (for methotrexate and hydroxychloroquine)will be prepared and prescribed in identical fashion as the methotrexate and hydroxychloroquine in the combination DMARD arm. | Drug | Placebo |
Primary outcome
Primary end point will be number of patients attaining Assessment of spondyloarthropathy international society 20 (ASAS20) response.
Time frame: 28 weeks
9 secondary outcomes
Improvement in Bath ankylosing spondylitis disease activity index (BASDAI)
Time frame: 28 weeks
Improvement in Bath ankylosing spondylitis functional index (BASFI)
Time frame: 28 weeks
Improvement in Bath ankylosing spondylitis metrology index (BASMI)
Time frame: 28 weeks
Improvement in Maastricht Ankylosing Spondylitis Enthesitis Index
Time frame: 28 weeks
Patient pain and global assessment of disease
Time frame: 28 weeks
Physician assessment of pain and global disease
Time frame: 28 weeks
change in Short form 36 (SF-36) and health assessment questionnaire (HAQ) parameters
Time frame: 28 weeks
improvement in erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP)
Time frame: 28 weeks
Reduction in non steroidal anti-inflammatory drug (NSAID) dose
Time frame: 28 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Mar 2013.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Vikas Agarwal, MD, DM principal investigator
SGPGIMS
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Methotrexate, Hydroxychloroquine in people with Seronegative Spondyloarthropathies, run by Sanjay Gandhi Postgraduate Institute of Medical Sciences at 1 site in India.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 22 Mar 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in India. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Primary end point will be number of patients attaining Assessment of spondyloarthropathy international society 20 (ASAS20) response. (time frame: 28 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Mar 2013.