Spacing of TNF-blocker Injections in Rheumatoid Arthritis Study (STRASS)

February 1, 2012 updated by: Assistance Publique - Hôpitaux de Paris

Effect of TNF-blocker Injections Spacing on Rheumatoid Arthritis Inflammatory Activity in Patients in Clinical Remission or Low Disease Activity

Remission is nowadays the recommended therapeutic objective in rheumatoid arthritis. Once this objective is achieved thanks to TNF-blockers, the optimal therapeutic strategy remains unclear, either therapeutic maintenance or progressive DMARD tapering (with a non quantified risk of disease flare).

STRASS is a 2-arm randomized controlled trial aiming to compare these 2 strategies (DMARD maintenance or progressive spacing of TNF-blocker injections) in terms of remission maintenance, relapse risk, safety issues and economic consequences during 18 months.

The inclusion period is 18 months, between September 2008 and February 2010.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Rationale:

Clinical remission is the therapeutic objective in rheumatoid arthritis, as recommended by professional practice guidelines. Once this objective is achieved with subcutaneous TNF-blockers, the maintenance of such treatments - highly efficacious but expensive and potentially toxic - is debated. To date, no reliable data are available to estimate the risk - benefice ratio associated with either their maintenance or their tapering.

Objectives:

In RA patients in remission, the study aims:

  1. To compare RA inflammatory activity based on repeated measures of the Disease Activity Score (DAS) depending on 2 therapeutic schemes: (M) maintenance of unchanged TNF-blockers or (S) tapering of TNF-blocker doses by progressive spacing of subcutaneous injections according to a predefined algorithm;
  2. To estimate the cost - effectiveness ratio of TNF-blocker spacing as compared to TNF-blocker maintenance.

Inclusion criteria:

  • Patients aged 18 or more, diagnosed with RA according to the 1987 ACR classification criteria;
  • RA treated with subcutaneous TNF-blockers (etanercept or adalimumab) at stable and standard dosage for 1 year or more, as monotherapy or associated with stable conventional DMARD;
  • RA in clinical remission, defined as a stable DAS28 ≤ 2.6 for 6 months or more, without any structural damage progression on X-rays (local reading by the treating rheumatologist);

Exclusion criteria:

  • Treatment with steroids;
  • progressing disease on X-rays during the year preceding the trial;
  • surgery planed in the 18 coming months;
  • pregnancy;
  • on-going neoplastic disease;
  • other auto-immune disorders different from RA;
  • inability to speak or understand French;
  • absence of signed informed consent;
  • absence of medical insurance coverage.

Sample size calculation: 250 patients, 125 for each arm.

Centers: 22 inclusion centers in France.

Research duration: 3 years. Participation duration for each patient: 18 months. Inclusion period duration: 18 months (Sep 2008 - Feb 2010).

Methods:

Equivalence trial, prospective, randomized, controlled versus usual care, patients remaining blinded of the tested hypotheses.

Investigators assessing disease activity remain blind of the protocol arm. The statistical analysis will be based on a mixed linear model taking into account repeated data.

Randomization:

Computer-assisted randomization (CleanWeb software) by blocks of unequal size, stratified on inclusion centers and TNF-blocker molecule.

Primary endpoint:

RA inflammatory activity over 18 months estimated by DAS28 repeated measures.

Secondary endpoints:

  • RA inflammatory activity over 18 months estimated by DAS44 repeated measures;
  • Cost - Effectiveness ratio calculated as: (CostMaintenance - CostSpacing) / (EfficacyMaintenance - EfficacySpacing);
  • Relapse rate over 18 months based on Kaplan Meier survival analysis;
  • Functional impairment based on HAQ index;
  • Health-related quality of life on SF-36;
  • Utility based on EQ-5D instrument;
  • Structural damage progression over 18 months assessed with the van der HEIJDE-modified Sharp score (SHS);
  • Safety;
  • Determinants of maintained remission or relapse after TNF-blocker injection spacing.

Research time sheet:

Clinical, biological and imaging follow-up is based on guidelines-recommended RA follow-up.

Biological work-ups specifically dedicated to the research represent 80 mL. The others are part of usual care and may be performed in non-hospital laboratories.

Expected results and perspectives:

The trial aims to test the feasibility and the risk - benefit ratio of a step-down strategy for TNF-blockers in the course of RA.

Study Type

Interventional

Enrollment (Actual)

250

Phase

  • 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

  • France
      • Paris, France, 75013
        • Service de rhumatologie / Groupe hospitalier Pitié Salpêtrière

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

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Patients aged 18 or more, diagnosed with RA according to the 1987 ACR classification criteria;
  • RA treated with subcutaneous TNF-blockers (étanercept or adalimumab) at stable and standard dosage for 1 year or more, as monotherapy or associated with stable conventional DMARD;
  • RA in clinical remission, defined as a stable DAS28 ≤ 2.6 for 6 months or more, without any structural damage progression on X-rays (local reading by the treating rheumatologist);

Exclusion Criteria:

  • Treatment with steroids;
  • progressing disease on X-rays during the year preceding the trial;
  • surgery planed in the 18 coming months;
  • pregnancy;
  • on-going neoplastic disease;
  • other auto-immune disorders different from RA;
  • inability to speak or understand French;
  • absence of signed informed consent;
  • absence of medical insurance coverage.

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: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: 1-M : Maintenance
Usual care
Drug: DMARD maintenance
DMARD maintenance
Experimental: 2 -S : Spacing of TNF-blocker injections
Spacing of TNF-blocker injections
Drug: progressive spacing of TNF-blocker injections

Experimental arm

Progressive spacing of TNF-blocker injections according to the following algorithm :

  • if DAS28 ≤ 2.6 at trimestrial assessment: go for step N+1
  • if DAS28 > 2.6 and DAS28 change ≤ 0.6: continue at step N
  • if DAS28 > 2.6 and DAS28 change > 0.6 : return to step N-1 (relapse as defined by the European expert consensus).

Step 0 (inclusion) :

  • Adalimumab 40 mg / 14 days
  • Etanercept 50 mg / 7 days

Step 1 :

  • Adalimumab 40 mg / 21 days
  • Etanercept 50 mg / 10 days

Step 2 :

  • Adalimumab 40 mg / 28 days
  • Etanercept 50 mg / 14 days

Step 3 :

  • Adalimumab 40 mg / 42 days
  • Etanercept 50 mg / 21 days

Step 4 :

  • TNF-blocker stop
Other Names:
  • Spacing (S)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
RA inflammatory activity over 18 months based on repeated DAS28 measures
Time Frame: over 18 months
over 18 months

Secondary Outcome Measures

Outcome Measure
Time Frame
RA inflammatory activity over 18 months estimated by DAS44 repeated measures
Time Frame: over 18 months
over 18 months
Cost - Effectiveness ratio calculated as: (CostMaintenance - CostSpacing) / (EfficacyMaintenance - EfficacySpacing);
Time Frame: during the study
during the study
Relapse rate over 18 months based on Kaplan Meier survival analysis
Time Frame: over 18 months
over 18 months
Functional impairment based on HAQ index
Time Frame: during the study
during the study
Health-related quality of life on SF-36
Time Frame: during the study
during the study
Utility based on EQ-5D instrument
Time Frame: during the study
during the study
Structural damage progression over 18 months assessed with the van der HEIJDE-modified Sharp score (SHS)
Time Frame: over 18 months
over 18 months
Determinants of maintained remission or relapse after TNF-blocker injection spacing
Time Frame: during teh study
during teh study

Collaborators and Investigators

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

Sponsor

Assistance Publique - Hôpitaux de Paris

Collaborators

French Society of Rheumatology

Investigators

  • Principal Investigator: Bruno FAUTREL, MD, PhD, Assistance Publique - Hôpitaux de Paris

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

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

September 1, 2008

Primary Completion (Actual)

September 1, 2011

Study Completion (Actual)

September 1, 2011

Study Registration Dates

First Submitted

October 27, 2008

First Submitted That Met QC Criteria

October 27, 2008

First Posted (Estimate)

October 28, 2008

Study Record Updates

Last Update Posted (Estimate)

February 2, 2012

Last Update Submitted That Met QC Criteria

February 1, 2012

Last Verified

October 1, 2008

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • AOM 07127

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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