RHEUMATOID ARTHRITISPhase 3NCT01724268
Corticosteroids and Anti TNF in Methotrexate Inadequate Responder Rheumatoid Arthritis Patient
A Phase 3 study testing Pred + Meth and Anti TNF + Meth in people with RHEUMATOID ARTHRITIS, run by Hamad Medical Corporation at 1 site in Qatar.
Trial summary
Compare the efficacy of adding small doses of prednisolone (10 mg) daily to the efficacy of adding one of the available anti TNF in the treatment of methotrexate inadequate responder rheumatoid arthritis patient. Hypothesis: Methotrexate + Prednisolone vs. Methotrexate + anti TNF Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- RHEUMATOID ARTHRITIS
- What is being tested?
- Pred + Meth and Anti TNF + Meth
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 80 participants
- Where
- 1 siteQatar
- Study dates
- May 2012to Sep 2014
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Males or females aged 18 years or older.
- Satisfies the 2010 American College of Rheumatology/European League Against Rheumatism Criteria for Rheumatoid Arthritis.
- Rheumatoid arthritis of < 2 years duration
- Has active disease at the time of enrollment. (Modified Disease Activity Score ≥ 3.2)
- Demonstrates functional status of class I, II, or III as defined by American College of Rheumatology revised criteria.
- Is on methotrexate 25 mg weekly or the maximum tolerated dose, therapy should be for at least 3 months duration and on the highest tolerated dose for the last 4 weeks.
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- Is able and willing to self-inject study drug if assigned to the injectable drug group or have a designee who can do so.
- Is PPD negative (skin test for TB exposure) or completed ≥1 month of latent TB treatment if PPD ≥ 5 or quantiferon (blood test for TB exposure) positive.
- Is having normal Chest X-Ray.
- Is Hepatitis B Negative.
- Not on NSAID (e.g. Ibuprofen) or receiving the same dose of the same NSAID throughout the study period unless side effects occur
- All patients in childbearing age should use effective birth control methods
- Is capable of understanding and signing an informed consent form.
Who cannot join
- Received any previous treatment with Tumor Necrosis Factor inhibitor or other biologic treatments for Rheumatoid Arthritis (such as abatacept, rituximab, tocilizumab, or Anakinra).
- Received any previous treatment with oral corticosteroids (e.g. prednisolone)
- Has a known or expected allergy, contraindication, or hypersensitivity to the medications tested.
- Any major illness/condition that, in the investigator's judgment, will substantially increase the risk associated with the subject's participation in, and completion of, the study, or could preclude the evaluation of the subject's response.
- Received any of the following within 4 weeks before baseline visit: leflunomide, hydroxychloroquine, chloroquine, cyclosporine, sulphasalazine, auranofin, intramuscular gold, azathioprine, minocycline, or D-penicillamine
- Received cyclophosphamide within 6mths before screening visit.
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- Received any live (attenuated) vaccines within 4 weeks before screening visit.
- Received intra-articular or subcutaneous corticosteroid injection within 4 weeks before screening visit.
- Received bolus intramuscular/ intravenous treatment with corticosteroids (> 20mg prednisone or equivalent) within 4 weeks before screening visit.
Trial locations and contacts
1 site in 1 country.
Qatar1 site, 1 recruiting
- Recruiting
Hamad General Hospital
Doha, Ad Dawha, 3050
MAGDI H ABDELRAHMAN, MBBS, mrahman1@hmc.org.qa
About this study
Official title: Randomized Controlled Clinical Trial of Low Dose Corticosteroids vs Anti TNF Treatment in Methotrexate Inadequate Responder Rheumatoid Arthritis Patient- a Pilot Study
Compare the efficacy of adding small doses of prednisolone (10 mg) daily to the efficacy of adding one of the available anti TNF in the treatment of methotrexate inadequate responder rheumatoid arthritis patient.
Hypothesis:
Methotrexate + Prednisolone vs. Methotrexate + anti TNF
Read the detailed description
Rheumatoid arthritis (RA) is an autoimmune disease that causes chronic inflammation of the joints and of the tissues around the joints, as well as in other organs in the body. Early diagnosis of rheumatoid arthritis and early aggressive treatment can help prevent joint damage, deformity and disability.
The management of RA rests on several principles; drug treatment, which comprise disease modifying anti-rheumatic drugs (DMARDS), but also non-steroidal anti-inflammatory drugs (NSAIDs) and glucocorticoids (GCs), as well as non-pharmacological measures, such as physical, occupational and psychological therapeutic approaches, together may lead to therapeutic success. However, the mainstay of RA treatment is the application of DMARDs. Methotrexate (MTX) is the anchor drug in the management of RA and has been used for many decades.
New and highly effective DMARDS have continued to emerge until the most recent years- in particular, biologic agents which target tumor necrosis factor, the interleukin 1 (IL -1) receptor, the IL-6 receptor, B lymphocytes and T cell co-stimulation. Furthermore, treatment strategies have changed during this period, initially by calling for early referral and early institution of DMARD treatment on the basis of respective evidence of clinical efficacy.
The EULAR (EUROPEAN LEAGUE AGAINST RHEUMATISM) recommendations for treatment of rheumatoid arthritis (3) emphasize that treatment should be aimed at reaching the target of remission or low disease activity (DAS 28 score ≤ 3.2) as soon as possible in every patient; as long as the target has not been reached, treatment should be adjusted by frequent (every 1-3 months) and strict monitoring.
MTX (1) should be part of the first treatment strategy in patients with active RA and when MTX contraindications (or intolerance) are present, other DMARDs should be considered.
GCs (1) added at low to moderately high doses to synthetic DMARD monotherapy (or combinations of synthetic DMARDs) provide benefit as initial short-term treatment, but should be tapered as rapidly as clinically feasible.
In a systematic review (4), GCs were found to be effective in relieving signs and symptoms and inhibiting radiographic progression, either as monotherapy or combination therapy.
In patients responding insufficiently to MTX and/or other synthetic DMARDs with or without GCs, biological DMARDs should be started (1); current practice would be to start a TNF inhibitor (adalimumab, certolizumab, etanercept, golimumab or infliximab) which should be combined with MTX.
In most of the studies which included GCs in the management of RA, it was included at the beginning of the study (1).
In a recent trial (2), Inclusion of low-dose prednisone from the start into a two-year MTX-based tight control treatment strategy for early RA increases both effectiveness (i.e. disease activity variables) and outcome (i.e. erosive joint damage) without increasing toxicity. It also reduces the need for (early) treatment with biologicals.
The anti TNF treatment is expensive and carries the risk of infection. To our knowledge, there is no study comparing the addition of small doses of steroids of steroids to the addition of anti TNF in patients who failed or did not tolerate the 25 mg of MTX.
The investigators have designed this study to compare the efficacy of adding small doses of prednisolone (10 mg) daily to the efficacy of adding one of the available anti TNF in patients who did not achieve remission on maximum tolerated MTX dose (up to 25 mg).
- Conditions
- RHEUMATOID ARTHRITIS
- Being tested
- Pred + Meth, Anti TNF + Meth
- Medical subject headings
- Arthritis, Rheumatoid
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Pred + MethDrug
Also called Prednisolone, Methotrexate
PREDNISOLONE 10mg orally ONCE DAILY and Methotrexate 25 mg / day
Anti TNF + MethDrug
| Study group | Role | What they receive |
|---|---|---|
| Pred + Meth | Experimental | Prednisolone : 10 mg daily
+ Methotrexate : 25 mg/ day
ARM 1 Treatment Arm Receives: Drug: Pred + Meth |
| Anti TNF + Meth | Active comparator | Etanrcept: 50 mg; Adalimumab: 40 mg; Infliximab: 3mg/kg
+ Methotrexate 25 mg per day Control Arm Receives: Drug: Anti TNF + Meth |
What is being measured
The primary outcome is the main question the study is designed to answer.
Disease activity score
DAS 28: Disease activity score, is a modification of the original DAS score, it divides disease activity into high, moderate, low disease activity, and remission (High disease activity is DAS28 >5.1, moderate is DAS28 of >3.2 to 5.1, low disease activity is DAS28 of 2.6 to 3.2, and remission is DAS28 <2.6).
Measured: 4 months
Secondary outcomes (1)
HAQ Score
HAQ Score: Health Assessment Questionnaire evaluates patients' ability to perform activities of daily living through their answers to 20 questions designed to assess upper or lower extremity use. These questions are organized into eight categories: dressing, rising, eating, walking, hygiene, reach, grip, and usual activities. Each question is answered on a four-level scale of impairment ranging from 0 to 3: 0 = no difficulty; 1 = some difficulty; 2 = much difficulty; and 3 = inability to do.
Measured: 4 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Nov 2012 (estimated)
- Study startMay 2012
- Primary completionMay 2014 (estimated)
- Study completionSep 2014 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for RHEUMATOID ARTHRITISStudies of the same condition, open and under way.
- More trials run by Hamad Medical CorporationThe sponsor's other registered studies.
- 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
- None (open label)
- Enrolment
- 80 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Hamad Medical Corporation
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- MAGDI H ABDELRAHMAN, MBBS, Principal investigator, Hamad Medical CorporationMOHAMMED M HAMMOUDEH, MD, Principal investigator, Hamad Medical Corporation
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01724268
- Sponsor's protocol ID
- 11224-12
- Status last verified
- Nov 2012
- First submitted
- 7 Nov 2012
- Last updated
- 9 Nov 2012
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 9 Nov 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Randomized Controlled Clinical Trial of Low Dose Corticosteroids vs Anti TNF Treatment in Methotrexate Inadequate Responder Rheumatoid Arthritis Patient- a Pilot Study
- ClinicalTrials.gov ID
- NCT01724268
- Acronym / sponsor ID
- 11224-12
- Conditions
- RHEUMATOID ARTHRITIS
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 80 participants (estimated)
- Lead sponsor
- Hamad Medical CorporationIndustry (pharma, biotech, devices)
- Study start
- May 2012
- Primary completion
- May 2014 (estimated)
- Study completion
- Sep 2014 (estimated)
- First posted
- 9 Nov 2012 (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.
Compare the efficacy of adding small doses of prednisolone (10 mg) daily to the efficacy of adding one of the available anti TNF in the treatment of methotrexate inadequate responder rheumatoid arthritis patient.
Hypothesis:
Methotrexate + Prednisolone vs. Methotrexate + anti TNF
Detailed description
Rheumatoid arthritis (RA) is an autoimmune disease that causes chronic inflammation of the joints and of the tissues around the joints, as well as in other organs in the body. Early diagnosis of rheumatoid arthritis and early aggressive treatment can help prevent joint damage, deformity and disability.
The management of RA rests on several principles; drug treatment, which comprise disease modifying anti-rheumatic drugs (DMARDS), but also non-steroidal anti-inflammatory drugs (NSAIDs) and glucocorticoids (GCs), as well as non-pharmacological measures, such as physical, occupational and psychological therapeutic approaches, together may lead to therapeutic success. However, the mainstay of RA treatment is the application of DMARDs. Methotrexate (MTX) is the anchor drug in the management of RA and has been used for many decades.
New and highly effective DMARDS have continued to emerge until the most recent years- in particular, biologic agents which target tumor necrosis factor, the interleukin 1 (IL -1) receptor, the IL-6 receptor, B lymphocytes and T cell co-stimulation. Furthermore, treatment strategies have changed during this period, initially by calling for early referral and early institution of DMARD treatment on the basis of respective evidence of clinical efficacy.
The EULAR (EUROPEAN LEAGUE AGAINST RHEUMATISM) recommendations for treatment of rheumatoid arthritis (3) emphasize that treatment should be aimed at reaching the target of remission or low disease activity (DAS 28 score ≤ 3.2) as soon as possible in every patient; as long as the target has not been reached, treatment should be adjusted by frequent (every 1-3 months) and strict monitoring.
MTX (1) should be part of the first treatment strategy in patients with active RA and when MTX contraindications (or intolerance) are present, other DMARDs should be considered.
GCs (1) added at low to moderately high doses to synthetic DMARD monotherapy (or combinations of synthetic DMARDs) provide benefit as initial short-term treatment, but should be tapered as rapidly as clinically feasible.
In a systematic review (4), GCs were found to be effective in relieving signs and symptoms and inhibiting radiographic progression, either as monotherapy or combination therapy.
In patients responding insufficiently to MTX and/or other synthetic DMARDs with or without GCs, biological DMARDs should be started (1); current practice would be to start a TNF inhibitor (adalimumab, certolizumab, etanercept, golimumab or infliximab) which should be combined with MTX.
In most of the studies which included GCs in the management of RA, it was included at the beginning of the study (1).
In a recent trial (2), Inclusion of low-dose prednisone from the start into a two-year MTX-based tight control treatment strategy for early RA increases both effectiveness (i.e. disease activity variables) and outcome (i.e. erosive joint damage) without increasing toxicity. It also reduces the need for (early) treatment with biologicals.
The anti TNF treatment is expensive and carries the risk of infection. To our knowledge, there is no study comparing the addition of small doses of steroids of steroids to the addition of anti TNF in patients who failed or did not tolerate the 25 mg of MTX.
The investigators have designed this study to compare the efficacy of adding small doses of prednisolone (10 mg) daily to the efficacy of adding one of the available anti TNF in patients who did not achieve remission on maximum tolerated MTX dose (up to 25 mg).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Pred + Meth | Experimental | Drug: Pred + MethPrednisolone : 10 mg daily + Methotrexate : 25 mg/ day ARM 1 Treatment Arm |
| Anti TNF + Meth | Active comparator | Drug: Anti TNF + MethEtanrcept: 50 mg; Adalimumab: 40 mg; Infliximab: 3mg/kg + Methotrexate 25 mg per day Control Arm |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- Males or females aged 18 years or older.
- Satisfies the 2010 American College of Rheumatology/European League Against Rheumatism Criteria for Rheumatoid Arthritis.
- Rheumatoid arthritis of < 2 years duration
- Has active disease at the time of enrollment. (Modified Disease Activity Score ≥ 3.2)
- Demonstrates functional status of class I, II, or III as defined by American College of Rheumatology revised criteria.
Key exclusion criteria (9 listed)
- Received any previous treatment with Tumor Necrosis Factor inhibitor or other biologic treatments for Rheumatoid Arthritis (such as abatacept, rituximab, tocilizumab, or Anakinra).
- Received any previous treatment with oral corticosteroids (e.g. prednisolone)
- Has a known or expected allergy, contraindication, or hypersensitivity to the medications tested.
- Any major illness/condition that, in the investigator's judgment, will substantially increase the risk associated with the subject's participation in, and completion of, the study, or could preclude the evaluation of the subject's response.
- Received any of the following within 4 weeks before baseline visit: leflunomide, hydroxychloroquine, chloroquine, cyclosporine, sulphasalazine, auranofin, intramuscular gold, azathioprine, minocycline, or D-penicillamine
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 |
|---|---|---|
| Pred + MethAlso: Prednisolone, MethotrexatePREDNISOLONE 10mg orally ONCE DAILY and Methotrexate 25 mg / day | Drug | Pred + Meth |
| Anti TNF + Meth | Drug | Anti TNF + Meth |
Primary outcome
Disease activity score
Time frame: 4 months
DAS 28: Disease activity score, is a modification of the original DAS score, it divides disease activity into high, moderate, low disease activity, and remission (High disease activity is DAS28 >5.1, moderate is DAS28 of >3.2 to 5.1, low disease activity is DAS28 of 2.6 to 3.2, and remission is DAS28 <2.6).
1 secondary outcome
HAQ Score
Time frame: 4 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Nov 2012.
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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.
MAGDI H ABDELRAHMAN, MBBS principal investigator
Hamad Medical Corporation
MOHAMMED M HAMMOUDEH, MD principal investigator
Hamad Medical Corporation
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 Pred + Meth and Anti TNF + Meth in people with RHEUMATOID ARTHRITIS, run by Hamad Medical Corporation at 1 site in Qatar.
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 13 inclusion and 9 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: status not confirmed, as of the sponsor's last update on 9 Nov 2012. 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 Qatar. 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. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Each site lists its own contact: choose the nearest one under Trial locations. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Disease activity score (time frame: 4 months). 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 9 Nov 2012.