Rituximab Versus Cyclophosphamide in Connective Tissue Disease-ILD (RECITAL)

October 6, 2021 updated by: Royal Brompton & Harefield NHS Foundation Trust

A Randomized, Double Blind Controlled Trial Comparing Rituximab Against Intravenous Cyclophosphamide in Connective Tissue Disease Associated Interstitial Lung Disease

Interstitial lung disease (ILD) is characterised by inflammation and scarring of the lung and is the leading cause of death in patients with systemic sclerosis, and contributes significantly to morbidity and mortality in many other connective tissue diseases (CTDs) such as polymyositis/dermatomyositis and mixed connective tissue disease. When ILD is extensive and/or progressive, immunosuppressive medication is often required to stabilize lung disease and alleviate symptoms. Current standard care for CTD associated ILD is extrapolated from studies performed in individuals with systemic sclerosis and comprises low dose corticosteroids and intravenous cyclophosphamide followed by oral azathioprine. In some individuals even this intensive immunosuppression is insufficient to prevent deterioration, and in a significant minority of affected individuals this results in respiratory failure and death. Rituximab has recently been reported as an effective 'rescue therapy' for stabilizing and even improving ILD in this patient group. Based on observations gained from this experience, the investigators believe that rituximab is a potential important alternative to current best therapy for this patient group. This study has therefore been initiated to evaluate the efficacy of rituximab (compared with standard therapy) in patients with progressive CTD related ILD.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

104

Phase

  • Phase 2
  • Phase 3

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

  • United Kingdom
      • London, United Kingdom, SW3 6NP
        • Royal Brompton Hospital

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 to 80 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Age 18 to 80 years at visit 1

  • A diagnosis of connective tissue disease, based on internationally accepted criteria, in one of the following categories21-24: (see Appendix 1 for details)

    • Systemic sclerosis
    • Idiopathic interstitial myopathy (including polymyositis/dermatomyositis)
    • Mixed connective tissue disease
  • Severe and/or progressive interstitial lung disease associated with the underlying connective tissue disease.
  • Chest HRCT performed within 12 months of study visit 1
  • Intention of the caring physician to treat the ILD with intravenous cyclophosphamide (with treatment indications including deteriorating symptoms attributable to ILD, deteriorating lung function tests, worsening gas exchange or extent of ILD at first presentation) and where there is a reasonable expectation that immunosuppressive treatment with stabilize or improve CTD-ILD. In individuals with scleroderma it is anticipated that subjects will fulfil the criteria for extensive disease defined by Goh et al19
  • Able to provide written informed consent

Exclusion Criteria:

  • Age <18 or >80 years.
  • Previous treatment with rituximab and/or intravenous cyclophosphamide
  • Known hypersensitivity to rituximab or cyclophosphamide or their components
  • Significant (in the opinion of the investigator) other organ co-morbidity including cardiac, hepatic or renal impairment
  • Co-existent obstructive pulmonary disease (e.g. asthma, COPD, emphysema) with pre bronchodilator FEV1/FVC < 70%
  • Patients at significant risk for infectious complications following immunosuppression, including; HIV positive or other immunodeficiency syndromes (including hypogammaglobulineamia)
  • Suspected or proven untreated tuberculosis
  • Viral hepatitis
  • Infection requiring antibiotic treatment in the preceding four weeks
  • Unexplained neurological symptoms (which may be suggestive of progressive mutifocal leukoencephalopathy; PML). Neurological symptoms arising as a consequence of the underlying CTD do not necessitate exclusion.
  • Other investigational therapy (participation in research trial) received within 8 weeks of visit 1
  • Immunosuppressive therapy (other than corticosteroids) received within 2 weeks of visit 1 (randomization)
  • Pregnant or breast feeding women, or women of child-bearing potential, not using a reliable contraceptive method
  • Unexplained haematuria, or previous bladder carcinoma
  • Unable to provide informed written consent

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: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Rituximab
1g given at baseline and two weeks.
Drug: Rituximab
Active Comparator: Cyclophosphamide
Intravenous dose of 600 mg/m2 body surface area. 6 doses given 4 weekly.
Drug: Cyclophosphamide

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Absolute change in FVC
Time Frame: 48 weeks
48 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
• Change from baseline in diffusing capacity for carbon monoxide (DLco)
Time Frame: 48 weeks
48 weeks
• Change from baseline in health related quality of life scores
Time Frame: 48 weeks
48 weeks
• Change from baseline in global disease activity score
Time Frame: 48 weeks
48 weeks
• Progression free survival
Time Frame: 48 weeks
composite endpoint of mortality, transplant, treatment failure or decline in FVC > 10% compared to baseline
48 weeks
• Adverse and serious adverse events (as defined in GCP)
Time Frame: 48 weeks
48 weeks

Collaborators and Investigators

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

Sponsor

Royal Brompton & Harefield NHS Foundation Trust

Collaborators

University College London Hospitals
Imperial College London
University of East Anglia

Investigators

  • Study Chair: Toby M Maher, MD PhD, Royal Brompton and Harefield Foundation NHS Trust

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 (Actual)

November 1, 2014

Primary Completion (Actual)

January 1, 2021

Study Completion (Actual)

January 1, 2021

Study Registration Dates

First Submitted

May 22, 2013

First Submitted That Met QC Criteria

May 24, 2013

First Posted (Estimate)

May 27, 2013

Study Record Updates

Last Update Posted (Actual)

October 7, 2021

Last Update Submitted That Met QC Criteria

October 6, 2021

Last Verified

October 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • RBHIPF004
  • 2012-003633-42 (EudraCT Number)

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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