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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01862926
Recruitment Status : Completed
First Posted : May 27, 2013
Last Update Posted : October 7, 2021
Imperial College London
University of East Anglia
University College London Hospitals
Information provided by (Responsible Party):
Royal Brompton & Harefield NHS Foundation Trust

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Interstitial Lung Disease Scleroderma Idiopathic Inflammatory Myositis Mixed Connective Tissue Disease Drug: Rituximab Drug: Cyclophosphamide Phase 2 Phase 3

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 104 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Randomized, Double Blind Controlled Trial Comparing Rituximab Against Intravenous Cyclophosphamide in Connective Tissue Disease Associated Interstitial Lung Disease
Actual Study Start Date : November 2014
Actual Primary Completion Date : January 2021
Actual Study Completion Date : January 2021

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

Primary Outcome Measures :
  1. Absolute change in FVC [ Time Frame: 48 weeks ]

Secondary Outcome Measures :
  1. • Change from baseline in diffusing capacity for carbon monoxide (DLco) [ Time Frame: 48 weeks ]
  2. • Change from baseline in health related quality of life scores [ Time Frame: 48 weeks ]
  3. • Change from baseline in global disease activity score [ Time Frame: 48 weeks ]
  4. • Progression free survival [ Time Frame: 48 weeks ]
    composite endpoint of mortality, transplant, treatment failure or decline in FVC > 10% compared to baseline

  5. • Adverse and serious adverse events (as defined in GCP) [ Time Frame: 48 weeks ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01862926

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United Kingdom
Royal Brompton Hospital
London, United Kingdom, SW3 6NP
Sponsors and Collaborators
Royal Brompton & Harefield NHS Foundation Trust
Imperial College London
University of East Anglia
University College London Hospitals
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Study Chair: Toby M Maher, MD PhD Royal Brompton and Harefield Foundation NHS Trust

Publications automatically indexed to this study by Identifier (NCT Number):
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Responsible Party: Royal Brompton & Harefield NHS Foundation Trust Identifier: NCT01862926    
Other Study ID Numbers: RBHIPF004
2012-003633-42 ( EudraCT Number )
First Posted: May 27, 2013    Key Record Dates
Last Update Posted: October 7, 2021
Last Verified: October 2021
Keywords provided by Royal Brompton & Harefield NHS Foundation Trust:
connective tissue disease
interstitial lung disease
pulmonary fibrosis
Additional relevant MeSH terms:
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Lung Diseases
Lung Diseases, Interstitial
Scleroderma, Systemic
Scleroderma, Diffuse
Connective Tissue Diseases
Mixed Connective Tissue Disease
Respiratory Tract Diseases
Skin Diseases
Muscular Diseases
Musculoskeletal Diseases
Neuromuscular Diseases
Nervous System Diseases
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Antineoplastic Agents, Immunological