Condition category
Respiratory
Date applied
01/04/2015
Date assigned
02/04/2015
Last edited
02/04/2015
Prospective/Retrospective
Retrospectively registered
Overall trial status
Ongoing
Recruitment status
Recruiting

Plain English Summary

Background and study aims
Interstitial lung disease (ILD), a condition that causes inflammation and scarring of the lungs, is the leading cause of death in systemic sclerosis (SSc), and a major cause of morbidity (or illness) in many other connective tissue diseases (CTDs) a group of conditions that are caused by over activity of the immune system. If connective tissue disease associated interstitial lung disease (CTD-ILD) is severe or progressive, immunosuppressive treatment (treatment used to damp down the immune system), such as intravenous cyclophosphamide, is required to suppress inflammation and minimise progressive lung scarring. Occasionally, even intensive standard immunosuppressive drugs fail to control lung inflammation, and progressive lung damage may develop that ultimately results in death. Rituximab, a novel immunosuppressive therapy, has been proven to be of benefit in suppressing inflammation associated with immune system over activity, including pulmonary inflammation in CTDs. In this study, we want to compare how well rituximab works compared to cyclophosphamide in treating patients with severe, progressive CTD-ILD.

Who can participate?
Adults diagnosed with CTD-ILD.

What does the study involve?
Participants are randomly allocated to one of two groups. Those in group 1 are given rituximab on day one of the study and then on day 14. They are then given a placebo four weeks into the study for 16 weeks. Those in group 2 are given cyclophosphamide every 4 weeks from day one of the study to week 20. On day 14, they are given a placebo. Lung function for all participants is assessed at the end of the study.

What are the possible benefits and risks of participating?
Not provided at time of registration

Where is the study run from?
Six NHS centres in the UK

When is the study starting and how long is it expected to run for?
November 2014 to August 2018

Who is funding the study?
National Institute for Health Research (UK)

Who is the main contact?
Dr Vicky Tsipouri

Trial website

Contact information

Type

Scientific

Primary contact

Dr Vicky Tsipouri

ORCID ID

Contact details

Royal Brompton & Harefield NHS Foundation Trust
Sydney Street
London
SW3 6NP
United Kingdom

Additional identifiers

EudraCT number

2012-003633-42

ClinicalTrials.gov number

Protocol/serial number

17594

Study information

Scientific title

A randomized, double blind controlled trial comparing rituximab against intravenous cyclophosphamide in connective tissue disease associated interstitial lung disease

Acronym

RECITAL

Study hypothesis

The aim of this trial is to we compare the effectiveness of rituximab against cyclophosphamide as first line therapy in patients with severe, progressive connective tissue disease associated interstitial lung disease (CTD-ILD).

Ethics approval

13/LO/0968

Study design

Randomised; Interventional; Design type: Not specified, Treatment

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Other

Trial type

Treatment

Patient information sheet

Not available in web format, please use the contact details to request a patient information sheet

Condition

Topic: Musculoskeletal disorders, Respiratory disorders; Subtopic: Musculoskeletal (all Subtopics), Respiratory (all Subtopics); Disease: Musculoskeletal, Respiratory

Intervention

Patients will be randomised on a 1:1 ratio to intravenous rituximab or intravenous cyclophosphamide.
1. Rituximab group: Rituximab will be given at a dose of 1000 mg at day 0 and day 14. At week 4 through to week 20 patients will receive placebo.
2. Cyclophosphamide group: Cyclophosphamide will be given at a dose of 600 mg/m2 body surface area every 4 weeks from day 0 through to week 20. At day 14 the group will receive placebo.

Intervention type

Other

Phase

Phase II/III

Drug names

Primary outcome measures

Change in forced vital capacity (FVC) at 24 weeks

Secondary outcome measures

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

Overall trial start date

03/11/2014

Overall trial end date

31/08/2018

Reason abandoned

Eligibility

Participant 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

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

Planned Sample Size: 116; UK Sample Size: 116

Participant 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

Recruitment start date

03/11/2014

Recruitment end date

31/08/2018

Locations

Countries of recruitment

United Kingdom

Trial participating centre

Royal Brompton & Harefield NHS Foundation Trust
Sydney Street
London
SW3 6NP
United Kingdom

Sponsor information

Organisation

Royal Brompton & Harefield NHS trust

Sponsor details

Royal Brompton Hospital
Sydney Street
London
SW3 6NP
United Kingdom

Sponsor type

Hospital/treatment centre

Website

Funders

Funder type

Government

Funder name

National Institute for Health Research

Alternative name(s)

NIHR

Funding Body Type

government organisation

Funding Body Subtype

Federal/National Government

Location

United Kingdom

Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes