Ignite Creation Date:
2024-05-06 @ 9:14 AM
Last Modification Date:
2024-10-26 @ 12:11 PM
Study NCT ID:
NCT02935387
Status:
TERMINATED
Last Update Posted:
2019-04-29
First Post:
2016-10-10
Brief Title:
REMission INDuction in Very Early Rheumatoid Arthritis
Sponsor:
UMC Utrecht
Organization:
UMC Utrecht
Study Overview
Official Title:
REMission INDuction in Very Early Rheumatoid Arthritis
Status:
TERMINATED
Status Verified Date:
2019-04
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
low recruitment rate
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
REMINDRA
Brief 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 Given the efficacy of TNFi it is conceivable that in early RA patients in remission with methotrexate MTXTNFi 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 im glucocorticoids GC and if not in remission the TNFi golimumab GOL phase I 34th or 1 year Patients in sustained remission on MTXGOL DAS2826 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 ACREUropean League Against Rheumatism EULAR criteria for RA with symptom duration 12 months naïve for anti-rheumatic drugs and glucocorticoids for RA DAS28 32
Intervention Patients in sustained remission defined as DAS2826 with max 4 swollen joints of the 44SJC at 2 consecutive visits 3 months apart on MTXGOL at the end of phase I after 24 weeks of treatment with MTXGOL will be randomized in a ratio of 11 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
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 im glucocorticoids GC and if not in remission the TNFi golimumab GOL phase I 34th or 1 year Patients in sustained remission on MTXGOL DAS2826 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 ACREUropean League Against Rheumatism EULAR criteria for RA with symptom duration 12 months naïve for anti-rheumatic drugs and glucocorticoids for RA DAS28 32
Intervention Patients in sustained remission defined as DAS2826 with max 4 swollen joints of the 44SJC at 2 consecutive visits 3 months apart on MTXGOL at the end of phase I after 24 weeks of treatment with MTXGOL will be randomized in a ratio of 11 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 MTXHCQGC in remission defined as DAS2826 at week 12 or week 24 after start of treatment
The proportion of patients on MTXGOL in sustained remission defined as DAS2826 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 im GC eg 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 eg 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 DAS2826 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 DAS2826 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 DAS2826 after retreatment with the last effective dose upon flare while tapering MTXGOL
Phase III Follow-up
The proportion of patients in drug-free sustained remission defined as DAS2826 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 DAS2826 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
Phase I Remission induction
The proportion of patients on MTXHCQGC in remission defined as DAS2826 at week 12 or week 24 after start of treatment
The proportion of patients on MTXGOL in sustained remission defined as DAS2826 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 im GC eg 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 eg 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 DAS2826 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 DAS2826 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 DAS2826 after retreatment with the last effective dose upon flare while tapering MTXGOL
Phase III Follow-up
The proportion of patients in drug-free sustained remission defined as DAS2826 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 DAS2826 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 Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None