Arthritis, RheumatoidPhase 4REMINDRANCT02935387
REMission INDuction in Very Early Rheumatoid Arthritis
A Phase 4 study testing Taper in people with Arthritis, Rheumatoid, run by UMC Utrecht at 2 sites in Netherlands.
Trial summary
Rheumatoid arthritis (RA) patients in remission with a combination of TNFinhibitors (TNFi) and methotrexate (MTX) often express their wish to stop MTX treatment because of side effects. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Arthritis, Rheumatoid
- What is being tested?
- Taper
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 53 participants
- Where
- 2 sitesNetherlands
- Study dates
- 21 Apr 2017to 9 Jan 2019
- Phase
- Phase 4
- 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
- Fulfilling 2010 ACR/EULAR criteria for RA.
- Patient reported symptom duration < 12 months
- Naïve for DMARD and biological treatment
- Naïve for previous use of glucocorticoids for RA
- DAS28 ≥3.2
Who cannot join
- Being pregnant or being a nursing women or a women of child bearing potential without (adequate) use of contraception
- Having any other inflammatory rheumatic disease than RA, except for secondary Sjögren's syndrome
Trial locations and contacts
2 sites in 1 country.
About this study
Rheumatoid arthritis (RA) patients in remission with a combination of TNFinhibitors (TNFi) and methotrexate (MTX) often express their wish to stop MTX treatment because of side effects. Given the efficacy of TNFi it is conceivable that in early RA patients in remission with methotrexate (MTX)/TNFi stepwise discontinuation of MTX prior to TNFi is superior in maintaining sustained remission and reaching drug free remission as compared to discontinuation of TNFi prior to MTX.
Objective: To investigate whether tapering MTX first, then the TNFi golimumab (GOL), is more efficacious than tapering GOL first, then MTX, in sustaining remission and reaching drug free remission.
Read more
Study design: multicenter, open label clinical trial in very early RA patients. Remission will be induced by an open label treat-to-target (T2T) remission induction protocol in clinical care: (MTX, hydroxychloroquine (HCQ), i.m. glucocorticoids (GC), and, if not in remission, the TNFi golimumab (GOL)) (phase I, 3/4th or 1 year). Patients in sustained remission on MTX/GOL (DAS28<2.6 with max 4 swollen joints of the 44 swollen joint count (SJC) at 2 consecutive visits 3 months apart) will be randomized to taper either MTX first, then GOL or GOL first, then MTX with as primary endpoint sustained (drug free) remission (phase II, 1 year). During 1 year additional follow-up maintenance of drug-free sustained remission will be investigated (phase III).
Study population: RA patients fulfilling 2010 American College of Rheumatology (ACR)/EUropean League Against Rheumatism (EULAR) criteria for RA, with symptom duration <12 months; naïve for anti-rheumatic drugs and glucocorticoids for RA; DAS28 ≥3.2.
Intervention: Patients in sustained remission (defined as DAS28<2.6 with max 4 swollen joints of the 44SJC at ≥ 2 consecutive visits 3 months apart) on MTX/GOL at the end of phase I (after 24 weeks of treatment with MTX/GOL) will be randomized in a ratio of 1:1 to taper medication as follows:
- Taper and stop GOL first during 24 weeks, then, if still in sustained remission, taper and stop MTX during 24 weeks
- Taper and stop MTX first during 24 weeks, then, if still in sustained remission, taper and stop GOL during 24 weeks The primary end point is the proportion of patients in sustained remission at week 24 after start of tapering of either MTX or GOL first. The main secondary end point is the proportion of patients in drug-free sustained remission, at week 48 after start of tapering.
Read the detailed description
Secondary endpoints:
Phase I (Remission induction):
- The proportion of patients on MTX/HCQ/GC in remission, defined as DAS28<2.6, at week 12 or week 24 after start of treatment.
- The proportion of patients on MTX/GOL in sustained remission, defined as DAS28<2.6 with max 4 swollen joints of the 44SJC at 2 consecutive visits 3 months apart, at week 24 after start of GOL treatment.
- Predictors of remission upon treatment with MTX, HCQ and a single injection of i.m. GC (e.g. smoking status, BMI, alcohol use, sex, disease duration, DAS28, Rheumatoid Factor (RF) -status, Anti-citrullinated protein antibody (ACPA) -status, presence of erosions)
- Predictors of remission upon treatment with MTX and GOL (e.g. smoking status, BMI, alcohol use, sex, disease duration, DAS28, RF-status, ACPA-status, presence of erosions)
Phase II (Tapering):
- The proportion of patients in sustained remission, defined as DAS28<2.6 with max 4 swollen joints of the 44SJC at 2 consecutive visits 3 months apart, at week 48 after start of tapering MTX first, then GOL or GOL first, then MTX.
- The proportion of patients in drug-free sustained remission, defined as DAS28<2.6 with max 4 swollen joints of the 44SJC at 2 consecutive visits 3 months apart while off anti-rheumatic treatment, at week 48 after start of tapering
- Mean disease activity, using the disease activity score assessing 28 joints (DAS28), at week 24 and week 48 after start of tapering
- Mean functional ability, using the Dutch consensus health assessment questionnaire (HAQ), at week 24 and week 48 after start of tapering
- Mean quality of life, using the visual analogue scale (VAS) of the EuroQol 5 dimensions (EQ5D) questionnaire, at week 24 and week 48 after start of tapering
- Mean anxiety and depression (using the Hospital Anxiety and Depression Scale (HADS)), at week 24 and week 48 after start of tapering
- Mean fatigue (using the Functional Assessment of Chronic Illness Therapy Fatigue (FACIT-F)), at week 24 and week 48 after start of tapering
- The proportion of serious adverse events (SAEs) in the two tapering strategies after 24 and after 48 weeks.
- The time until remission (DAS28<2.6) after retreatment with the last effective dose upon flare while tapering MTX/GOL.
Phase III (Follow-up):
- The proportion of patients in drug-free sustained remission, defined as DAS28<2.6 with max 4 swollen joints of the 44SJC at 2 consecutive visits 3 months apart while off anti-rheumatic treatment, at week 48 after discontinuation of both MTX and GOL
- The time until remission, defined as DAS28<2.6, after retreatment in clinical care upon flare
- The proportion of serious adverse events (SAEs) in the two tapering strategies at week 24 and week 48.
Phase II and III:
- Cost per extra patient in remission up to week 96 after start of tapering (end of phase III)
- Cost per Quality Adjusted life Year (QALY) gained up to week 96 after start of tapering (end of phase III)
Overall:
- The sensitivity and predictive value of the patient reported Routine Assessment of Patient Index Data 3 (RAPID3) to detect remission and flare
- Conditions
- Arthritis, Rheumatoid
- Being tested
- Taper
- Keywords
- Very early rheumatoid arthritis
- Medical subject headings
- Arthritis, Rheumatoid
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TaperOther
Taper
| Study group | Role | What they receive |
|---|---|---|
| Taper methotrexate, then golimumab | Experimental | Taper methotrexate 25>0mg/wk during 24 weeks, then, if still in sustained remission, taper golimumab 50>0mg/month during 24 weeks. Receives: Other: Taper |
| Taper golimumab, then methotrexate | Active comparator | Taper golimumab 50>0mg/month during 24 weeks, then, if still in sustained remission, taper methotrexate 25>0mg/wk during 24 weeks. Receives: Other: Taper |
What is being measured
The primary outcome is the main question the study is designed to answer.
proportion of patients in sustained remission
the proportion of patients in sustained remission at week 24 after start of tapering of either MTX or GOL first.
Measured: At week 24 after start of tapering
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Oct 2016 (estimated)
- Study start21 Apr 2017
- Primary completion9 Jan 2019
- Study completion9 Jan 2019
Why it stopped: low recruitment rate
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Arthritis, RheumatoidStudies of the same condition, open and under way.
- More trials run by UMC UtrechtThe 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 4
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 53 participants (actual)
Sponsor and investigators
- Lead sponsor
- UMC Utrecht
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Jacob M van Laar, UMC Utrecht
- Investigators
- Jacob M van Laar, Principal investigator, UMC Utrecht
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02935387
- Sponsor's protocol ID
- REMINDRA
- Acronym
- REMINDRA
- Status last verified
- Apr 2019
- First submitted
- 10 Oct 2016
- Last updated
- 29 Apr 2019
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 29 Apr 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- REMission INDuction in Very Early Rheumatoid Arthritis
- ClinicalTrials.gov ID
- NCT02935387
- Acronym / sponsor ID
- REMINDRA / REMINDRA
- Conditions
- Arthritis, Rheumatoid
- Keywords
- Very early rheumatoid arthritis
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: low recruitment rate
- Enrolment
- 53 participants (actual)
- Lead sponsor
- UMC UtrechtUniversity, hospital or other
- Study start
- 21 Apr 2017 (actual)
- Primary completion
- 9 Jan 2019 (actual)
- Study completion
- 9 Jan 2019 (actual)
- First posted
- 17 Oct 2016 (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.
Rheumatoid arthritis (RA) patients in remission with a combination of TNFinhibitors (TNFi) and methotrexate (MTX) often express their wish to stop MTX treatment because of side effects. Given the efficacy of TNFi it is conceivable that in early RA patients in remission with methotrexate (MTX)/TNFi stepwise discontinuation of MTX prior to TNFi is superior in maintaining sustained remission and reaching drug free remission as compared to discontinuation of TNFi prior to MTX.
Objective: To investigate whether tapering MTX first, then the TNFi golimumab (GOL), is more efficacious than tapering GOL first, then MTX, in sustaining remission and reaching drug free remission.
Study design: multicenter, open label clinical trial in very early RA patients. Remission will be induced by an open label treat-to-target (T2T) remission induction protocol in clinical care: (MTX, hydroxychloroquine (HCQ), i.m. glucocorticoids (GC), and, if not in remission, the TNFi golimumab (GOL)) (phase I, 3/4th or 1 year). Patients in sustained remission on MTX/GOL (DAS28<2.6 with max 4 swollen joints of the 44 swollen joint count (SJC) at 2 consecutive visits 3 months apart) will be randomized to taper either MTX first, then GOL or GOL first, then MTX with as primary endpoint sustained (drug free) remission (phase II, 1 year). During 1 year additional follow-up maintenance of drug-free sustained remission will be investigated (phase III).
Study population: RA patients fulfilling 2010 American College of Rheumatology (ACR)/EUropean League Against Rheumatism (EULAR) criteria for RA, with symptom duration <12 months; naïve for anti-rheumatic drugs and glucocorticoids for RA; DAS28 ≥3.2.
Intervention: Patients in sustained remission (defined as DAS28<2.6 with max 4 swollen joints of the 44SJC at ≥ 2 consecutive visits 3 months apart) on MTX/GOL at the end of phase I (after 24 weeks of treatment with MTX/GOL) will be randomized in a ratio of 1:1 to taper medication as follows:
- Taper and stop GOL first during 24 weeks, then, if still in sustained remission, taper and stop MTX during 24 weeks
- Taper and stop MTX first during 24 weeks, then, if still in sustained remission, taper and stop GOL during 24 weeks The primary end point is the proportion of patients in sustained remission at week 24 after start of tapering of either MTX or GOL first. The main secondary end point is the proportion of patients in drug-free sustained remission, at week 48 after start of tapering.
Detailed description
Secondary endpoints:
Phase I (Remission induction):
- The proportion of patients on MTX/HCQ/GC in remission, defined as DAS28<2.6, at week 12 or week 24 after start of treatment.
- The proportion of patients on MTX/GOL in sustained remission, defined as DAS28<2.6 with max 4 swollen joints of the 44SJC at 2 consecutive visits 3 months apart, at week 24 after start of GOL treatment.
- Predictors of remission upon treatment with MTX, HCQ and a single injection of i.m. GC (e.g. smoking status, BMI, alcohol use, sex, disease duration, DAS28, Rheumatoid Factor (RF) -status, Anti-citrullinated protein antibody (ACPA) -status, presence of erosions)
- Predictors of remission upon treatment with MTX and GOL (e.g. smoking status, BMI, alcohol use, sex, disease duration, DAS28, RF-status, ACPA-status, presence of erosions)
Phase II (Tapering):
- The proportion of patients in sustained remission, defined as DAS28<2.6 with max 4 swollen joints of the 44SJC at 2 consecutive visits 3 months apart, at week 48 after start of tapering MTX first, then GOL or GOL first, then MTX.
- The proportion of patients in drug-free sustained remission, defined as DAS28<2.6 with max 4 swollen joints of the 44SJC at 2 consecutive visits 3 months apart while off anti-rheumatic treatment, at week 48 after start of tapering
- Mean disease activity, using the disease activity score assessing 28 joints (DAS28), at week 24 and week 48 after start of tapering
- Mean functional ability, using the Dutch consensus health assessment questionnaire (HAQ), at week 24 and week 48 after start of tapering
- Mean quality of life, using the visual analogue scale (VAS) of the EuroQol 5 dimensions (EQ5D) questionnaire, at week 24 and week 48 after start of tapering
- Mean anxiety and depression (using the Hospital Anxiety and Depression Scale (HADS)), at week 24 and week 48 after start of tapering
- Mean fatigue (using the Functional Assessment of Chronic Illness Therapy Fatigue (FACIT-F)), at week 24 and week 48 after start of tapering
- The proportion of serious adverse events (SAEs) in the two tapering strategies after 24 and after 48 weeks.
- The time until remission (DAS28<2.6) after retreatment with the last effective dose upon flare while tapering MTX/GOL.
Phase III (Follow-up):
- The proportion of patients in drug-free sustained remission, defined as DAS28<2.6 with max 4 swollen joints of the 44SJC at 2 consecutive visits 3 months apart while off anti-rheumatic treatment, at week 48 after discontinuation of both MTX and GOL
- The time until remission, defined as DAS28<2.6, after retreatment in clinical care upon flare
- The proportion of serious adverse events (SAEs) in the two tapering strategies at week 24 and week 48.
Phase II and III:
- Cost per extra patient in remission up to week 96 after start of tapering (end of phase III)
- Cost per Quality Adjusted life Year (QALY) gained up to week 96 after start of tapering (end of phase III)
Overall:
- The sensitivity and predictive value of the patient reported Routine Assessment of Patient Index Data 3 (RAPID3) to detect remission and flare
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Taper methotrexate, then golimumab | Experimental | Other: TaperTaper methotrexate 25>0mg/wk during 24 weeks, then, if still in sustained remission, taper golimumab 50>0mg/month during 24 weeks. |
| Taper golimumab, then methotrexate | Active comparator | Other: TaperTaper golimumab 50>0mg/month during 24 weeks, then, if still in sustained remission, taper methotrexate 25>0mg/wk during 24 weeks. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Fulfilling 2010 ACR/EULAR criteria for RA.
- Patient reported symptom duration < 12 months
- Naïve for DMARD and biological treatment
- Naïve for previous use of glucocorticoids for RA
- DAS28 ≥3.2
Key exclusion criteria (2 listed)
- Being pregnant or being a nursing women or a women of child bearing potential without (adequate) use of contraception
- Having any other inflammatory rheumatic disease than RA, except for secondary Sjögren's syndrome
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 |
|---|---|---|
| TaperTaper | Other | Taper golimumab, then methotrexate, Taper methotrexate, then golimumab |
Primary outcome
proportion of patients in sustained remission
Time frame: At week 24 after start of tapering
the proportion of patients in sustained remission at week 24 after start of tapering of either MTX or GOL first.
Results and safety
The study was stopped early (reason given: low recruitment rate). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Apr 2019.
- Individual participant dataSharing planned: No
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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.
Jacob M van Laar principal investigator
UMC Utrecht
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Taper in people with Arthritis, Rheumatoid, run by UMC Utrecht at 2 sites in Netherlands.
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 5 inclusion and 2 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: stopped early, as of the sponsor's last update on 29 Apr 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Netherlands. 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
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 was stopped early (reason given: low recruitment rate). Results are not available in the source record.
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?
proportion of patients in sustained remission (time frame: At week 24 after start of tapering). 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 29 Apr 2019.