Rituximab versus cyclophosphamide in connective tissue disease-ILD
| ISRCTN | ISRCTN16474148 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN16474148 |
| EudraCT/CTIS number | 2012-003633-42 |
| ClinicalTrials.gov number | NCT01862926 |
| Secondary identifying numbers | 17594 |
- Submission date
- 01/04/2015
- Registration date
- 02/04/2015
- Last edited
- 10/05/2024
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Respiratory
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 January 2021 (updated 23/06/2021, previously: December 2020; updated 15/08/2019, previously: August 2018)
Who is funding the study?
National Institute for Health Research (UK)
Who is the main contact?
Veronica Tudor
V.Tudor@rbht.nhs.uk
(updated 15/08/2019, previously: Dr Vicky Tsipouri)
Contact information
Scientific
Royal Brompton & Harefield NHS Foundation Trust
Sydney Street
London
SW3 6NP
United Kingdom
| Phone | +44330 128 8854 |
|---|---|
| v.tudor@rbht.nhs.uk |
Study information
| Study design | Randomised; Interventional; Design type: Not specified, Treatment |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Other |
| Study type | Treatment |
| Participant information sheet | Not available in web format, please use the contact details to request a patient information sheet |
| Scientific title | A randomized, double blind controlled trial comparing rituximab against intravenous cyclophosphamide in connective tissue disease associated interstitial lung disease |
| Study 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(s) | 13/LO/0968 |
| Condition | Interstitial lung disease in people with severe connective tissue disease, including systemic sclerosis, idiopathic interstitial myopathy (including polymyositis/dermatomyositis) and mixed connective tissue disease |
| 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 | Drug |
| Pharmaceutical study type(s) | |
| Phase | Not Applicable |
| Drug / device / biological / vaccine name(s) | Rituximab, cyclophosphamide |
| Primary outcome measure | Change in forced vital capacity (FVC) at 24 weeks |
| Secondary outcome measures | Safety, change in diffusing capacity for carbon monoxide (DLco) |
| Overall study start date | 03/11/2014 |
| Overall study end date | 12/01/2021 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Sex | Both |
| Target number of participants | Planned Sample Size: 116; UK Sample Size: 116 |
| Total final enrolment | 104 |
| 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 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 | 31/05/2020 |
Locations
Countries of recruitment
- England
- United Kingdom
Study participating centre
London
SW3 6NP
United Kingdom
Sponsor information
Hospital/treatment centre
Royal Brompton Hospital
Sydney Street
London
SW3 6NP
England
United Kingdom
"ROR" |
https://ror.org/02218z997 |
|---|
Funders
Funder type
Government
Government organisation / National government
- Alternative name(s)
- National Institute for Health Research, NIHR Research, NIHRresearch, NIHR - National Institute for Health Research, NIHR (The National Institute for Health and Care Research), NIHR
- Location
- United Kingdom
Results and Publications
| Intention to publish date | 01/11/2022 |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Not provided at time of registration |
| Publication and dissemination plan | Planned publication in a high-impact peer-reviewed journal. |
| IPD sharing plan | Not provided at time of registration |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Protocol article | protocol | 15/06/2017 | 23/07/2019 | Yes | No |
| Results article | 11/11/2022 | 14/11/2022 | Yes | No | |
| HRA research summary | 28/06/2023 | No | No | ||
| Results article | 01/02/2024 | 10/05/2024 | Yes | No |
Editorial Notes
10/05/2024: Publication reference added.
14/11/2022: Publication reference added.
01/06/2022: The intention to publish date has been changed from 01/05/2022 to 01/11/2022.
13/12/2021: The intention to publish date was changed from 30/06/2021 to 01/05/2022.
23/06/2021: The following changes have been made:
1. The overall trial end date has been changed from 31/05/2021 to 12/01/2021 and the plain English summary has been updated to reflect this change.
2. The publication and dissemination plan has been added.
25/05/2020: The following changes have been made:
1. The recruitment end date has been changed from 24/02/2020 to 31/05/2020.
2. The total final enrolment number has been changed from "101" to "104".
25/05/2020: The following changes have been made:
1. The recruitment end date has been changed from 31/05/2020 to 24/02/2020.
2. The total final enrolment number has been changed from "19" to "101".
21/01/2020: The condition has been changed from "Topic: Musculoskeletal disorders, Respiratory disorders; Subtopic: Musculoskeletal (all Subtopics), Respiratory (all Subtopics); Disease: Musculoskeletal, Respiratory" to "Interstitial lung disease in people with connective tissue disease, including systemic sclerosis, idiopathic interstitial myopathy (including polymyositis/dermatomyositis) and mixed connective tissue disease" following a request from the NIHR.
15/01/2020: The following changes have been made:
1. The recruitment end date has been changed from 31/12/2019 to 31/05/2020.
2. The overall trial end date has been changed from 31/12/2020 to 31/05/2021.
15/08/2019: The following changes were made to the trial record:
1. The recruitment end date was changed from 31/08/2018 to 31/12/2019.
2. The overall end date was changed from 31/08/2018 to 31/12/2020.
3. The intention to publish date was added.
4. The plain English summary was updated to reflect these changes.
5. The total final enrolment was added.
6. The scientific contact was changed from Dr Vicky Tsipouri to Veronica Tudor.
23/07/2019: The following changes were made to the trial record:
1. ClinicalTrials.gov number added.
2. Publication reference added.
