Rituximab versus cyclophosphamide in connective tissue disease-ILD

Not Applicable

Completed

• Conditions: Interstitial lung disease in people with severe connective tissue disease, including systemic sclerosis, idiopathic interstitial myopathy (including polymyositis/dermatomyositis) and mixed connective tissue disease; Respiratory

• Registration Number: ISRCTN16474148
• Lead Sponsor: Royal Brompton & Harefield NHS trust

Brief Summary

2017 Protocol article in https://www.ncbi.nlm.nih.gov/pubmed/28619061 protocol (added 23/07/2019) 2022 Results article in https://doi.org/10.1016/S2213-2600(22)00359-9 (added 14/11/2022) 2024 Results article in https://doi.org/10.3310/LYWQ8541 (added 10/05/2024)

Detailed Description

Not available

Study Timeline

• Study Start: 2015-04-02
• Study Completion: 2021-01-12
• Last Update Posted: 21 May 2024

Recruitment & Eligibility

• Status: Completed
• Sex: All
• Target Recruitment: 104

Inclusion Criteria

Subjects will be recruited prospectively from rheumatology or interstitial lung disease units at 6 UK centres.

1. A diagnosis of connective tissue disease, based on internationally accepted criteria, in one of the following categories:
1.1. Systemic sclerosis
1.2. Idiopathic interstitial myopathy (including polymyositis/dermatomyositis)
1.3. Mixed connective tissue disease
2. Severe and/or progressive interstitial lung disease associated with the underlying connective tissue disease.
3. Chest HRCT performed within 12 months of randomisation
4. 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 will stabilize or improve CTD-ILD
5. Written informed consent

Exclusion Criteria

1. Age <18 or >80 years.
2. Previous treatment with rituximab and/or intravenous cyclophosphamide
3. Known hypersensitivity to rituximab or cyclophosphamide or their components
4. Significant (in the opinion of the investigator) other organ co-morbidity including cardiac, hepatic or renal impairment
5, Co-existent obstructive pulmonary disease (e.g. asthma, COPD, emphysema) with pre bronchodilator FEV1/FVC <70%
6, Patients at significant risk for infectious complications following immunosuppression including HIV positive or other immunodeficiency syndromes (including hypogammaglobulineamia)
7. Suspected or proven untreated tuberculosis
8. Viral hepatitis
9. Infection requiring antibiotic treatment in the preceding four weeks
10. Unexplained neurological symptoms (which may be suggestive of progressive mutifocal leukoencephalopathy; PML).
11. Other investigational therapy (participation in research trial) received within 8 weeks of randomisation
12. Immunosuppressive or CTD disease modifying therapy (other than corticosteroids) received within 2 weeks of randomisation
13. Pregnant or breast feeding women, or women of child-bearing potential, not using a reliable contraceptive method for up to 12 months following IMP
14. Unexplained haematuria, or previous bladder carcinoma
15. CT scan > 12 months from randomisation
16. Unable to provide informed written consent

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Change in forced vital capacity (FVC) at 24 weeks

Secondary Outcome Measures

Name	Time	Method
Safety, change in diffusing capacity for carbon monoxide (DLco)