REMission INDuction in Very Early Rheumatoid Arthritis (REMINDRA)

April 25, 2019 updated by: Jacob M van Laar, UMC Utrecht

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Terminated

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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 Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
53

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Netherlands
      • Goes, Netherlands
        • Reumazorg Zuidwest Nederland
      • Utrecht, Netherlands
        • UMC Utrecht

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: PREVENTION
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: NONE

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Taper methotrexate, then golimumab
Taper methotrexate 25>0mg/wk during 24 weeks, then, if still in sustained remission, taper golimumab 50>0mg/month during 24 weeks.
Other: Taper
Taper
Active Comparator: Taper golimumab, then methotrexate
Taper golimumab 50>0mg/month during 24 weeks, then, if still in sustained remission, taper methotrexate 25>0mg/wk during 24 weeks.
Other: Taper
Taper

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
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.
At week 24 after start of tapering

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
UMC Utrecht

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Jacob M van Laar, UMC Utrecht

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
April 21, 2017

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
January 9, 2019

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
January 9, 2019

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
October 10, 2016

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 13, 2016

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
October 17, 2016

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
April 29, 2019

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 25, 2019

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
April 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • REMINDRA

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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