Interstitial Lung DiseasePhase 2/3RECITALNCT01862926
Rituximab Versus Cyclophosphamide in Connective Tissue Disease-ILD
A Phase 2/3 study testing Rituximab and Cyclophosphamide in people with Interstitial Lung Disease and Scleroderma, run by Royal Brompton & Harefield NHS Foundation Trust at 1 site in United Kingdom.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Interstitial Lung Disease, Scleroderma, Idiopathic Inflammatory Myositis
- What is being tested?
- Rituximab and Cyclophosphamide
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 104 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- Nov 2014to Jan 2021
- Phase
- Phase 2/3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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
Who cannot join
- 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)
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- 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
Trial locations and contacts
1 site in 1 country.
About this study
Official title: 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.
- Conditions
- Interstitial Lung Disease, Scleroderma, Idiopathic Inflammatory Myositis, Mixed Connective Tissue Disease
- Being tested
- Rituximab, Cyclophosphamide
- Keywords
- connective tissue disease, interstitial lung disease, pulmonary fibrosis, rituximab, scleroderma, polymyositis, dermatomyositis
- Medical subject headings
- Lung Diseases, Interstitial, Scleroderma, Diffuse, Myositis, Mixed Connective Tissue Disease, Connective Tissue Diseases, Pulmonary Fibrosis, Polymyositis, Dermatomyositis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RituximabDrug
CyclophosphamideDrug
| Study group | Role | What they receive |
|---|---|---|
| Rituximab | Experimental | 1g given at baseline and two weeks. Receives: Drug: Rituximab |
| Cyclophosphamide | Active comparator | Intravenous dose of 600 mg/m2 body surface area. 6 doses given 4 weekly. Receives: Drug: Cyclophosphamide |
What is being measured
The primary outcome is the main question the study is designed to answer.
Absolute change in FVC
Measured: 48 weeks
Secondary outcomes (5)
• Change from baseline in diffusing capacity for carbon monoxide (DLco)
Measured: 48 weeks
• Change from baseline in health related quality of life scores
Measured: 48 weeks
• Change from baseline in global disease activity score
Measured: 48 weeks
• Progression free survival
composite endpoint of mortality, transplant, treatment failure or decline in FVC > 10% compared to baseline
Measured: 48 weeks
• Adverse and serious adverse events (as defined in GCP)
Measured: 48 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 May 2013 (estimated)
- Study startNov 2014
- Primary completionJan 2021
- Study completionJan 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for Interstitial Lung DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 104 participants (actual)
Sponsor and investigators
- Lead sponsor
- Royal Brompton & Harefield NHS Foundation Trust
- Sponsor type
- University, hospital or other
- Collaborators
- Imperial College London, University of East Anglia, University College London Hospitals
- Responsible party
- Sponsor
- Investigators
- Toby M Maher, MD PhD, Study chair, Royal Brompton and Harefield Foundation NHS Trust
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01862926
- Sponsor's protocol ID
- RBHIPF004
- Other IDs
- 2012-003633-42
- Acronym
- RECITAL
- Status last verified
- Oct 2021
- First submitted
- 22 May 2013
- Last updated
- 7 Oct 2021
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Tyndall AJ, Bannert B, Vonk M, Airo P, Cozzi F, Carreira PE, Bancel DF, Allanore Y, Muller-Ladner U, Distler O, Iannone F, Pellerito R, Pileckyte M, Miniati I, Ananieva L, Gurman AB, Damjanov N, Mueller A, Valentini G, Riemekasten G, Tikly M, Hummers L, Henriques MJ, Caramaschi P, Scheja A, Rozman B, Ton E, Kumanovics G, Coleiro B, Feierl E, Szucs G, Von Muhlen CA, Riccieri V, Novak S, Chizzolini C, Kotulska A, Denton C, Coelho PC, Kotter I, Simsek I, de la Pena Lefebvre PG, Hachulla E, Seibold JR, Rednic S, Stork J, Morovic-Vergles J, Walker UA. Causes and risk factors for death in systemic sclerosis: a study from the EULAR Scleroderma Trials and Research (EUSTAR) database. Ann Rheum Dis. 2010 Oct;69(10):1809-15. doi: 10.1136/ard.2009.114264. Epub 2010 Jun 15.
PubMed 20551155Hoyles RK, Ellis RW, Wellsbury J, Lees B, Newlands P, Goh NS, Roberts C, Desai S, Herrick AL, McHugh NJ, Foley NM, Pearson SB, Emery P, Veale DJ, Denton CP, Wells AU, Black CM, du Bois RM. A multicenter, prospective, randomized, double-blind, placebo-controlled trial of corticosteroids and intravenous cyclophosphamide followed by oral azathioprine for the treatment of pulmonary fibrosis in scleroderma. Arthritis Rheum. 2006 Dec;54(12):3962-70. doi: 10.1002/art.22204.
PubMed 17133610Keir GJ, Maher TM, Hansell DM, Denton CP, Ong VH, Singh S, Wells AU, Renzoni EA. Severe interstitial lung disease in connective tissue disease: rituximab as rescue therapy. Eur Respir J. 2012 Sep;40(3):641-8. doi: 10.1183/09031936.00163911. Epub 2012 Jan 26.
PubMed 22282550Goh NS, Desai SR, Veeraraghavan S, Hansell DM, Copley SJ, Maher TM, Corte TJ, Sander CR, Ratoff J, Devaraj A, Bozovic G, Denton CP, Black CM, du Bois RM, Wells AU. Interstitial lung disease in systemic sclerosis: a simple staging system. Am J Respir Crit Care Med. 2008 Jun 1;177(11):1248-54. doi: 10.1164/rccm.200706-877OC. Epub 2008 Mar 27.
PubMed 18369202Maher TM, Tudor VA, Saunders P, Gibbons MA, Fletcher SV, Denton CP, Hoyles RK, Parfrey H, Renzoni EA, Kokosi M, Wells AU, Ashby D, Szigeti M, Molyneaux PL; RECITAL Investigators. Rituximab versus intravenous cyclophosphamide in patients with connective tissue disease-associated interstitial lung disease in the UK (RECITAL): a double-blind, double-dummy, randomised, controlled, phase 2b trial. Lancet Respir Med. 2023 Jan;11(1):45-54. doi: 10.1016/S2213-2600(22)00359-9. Epub 2022 Nov 11.
PubMed 36375479Saunders P, Tsipouri V, Keir GJ, Ashby D, Flather MD, Parfrey H, Babalis D, Renzoni EA, Denton CP, Wells AU, Maher TM. Rituximab versus cyclophosphamide for the treatment of connective tissue disease-associated interstitial lung disease (RECITAL): study protocol for a randomised controlled trial. Trials. 2017 Jun 15;18(1):275. doi: 10.1186/s13063-017-2016-2.
PubMed 28619061
Study at a glance
From the registry record, last updated by the sponsor on 7 Oct 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Double Blind Controlled Trial Comparing Rituximab Against Intravenous Cyclophosphamide in Connective Tissue Disease Associated Interstitial Lung Disease
- ClinicalTrials.gov ID
- NCT01862926
- Acronym / sponsor ID
- RECITAL / RBHIPF004
- Conditions
- Interstitial Lung Disease, Scleroderma, Idiopathic Inflammatory Myositis, Mixed Connective Tissue Disease
- Keywords
- connective tissue disease, interstitial lung disease, pulmonary fibrosis, rituximab, scleroderma, polymyositis, dermatomyositis
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 104 participants (actual)
- Lead sponsor
- Royal Brompton & Harefield NHS Foundation TrustUniversity, hospital or other
- Collaborators
- Imperial College London, University of East Anglia, University College London Hospitals
- Study start
- Nov 2014 (actual)
- Primary completion
- Jan 2021 (actual)
- Study completion
- Jan 2021 (actual)
- First posted
- 27 May 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Rituximab | Experimental | Drug: Rituximab1g given at baseline and two weeks. |
| Cyclophosphamide | Active comparator | Drug: CyclophosphamideIntravenous dose of 600 mg/m2 body surface area. 6 doses given 4 weekly. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- 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)
- 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
Key exclusion criteria (15 listed)
- 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%
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Rituximab | Drug | Rituximab |
| Cyclophosphamide | Drug | Cyclophosphamide |
Primary outcome
Absolute change in FVC
Time frame: 48 weeks
5 secondary outcomes
• Change from baseline in diffusing capacity for carbon monoxide (DLco)
Time frame: 48 weeks
• Change from baseline in health related quality of life scores
Time frame: 48 weeks
• Change from baseline in global disease activity score
Time frame: 48 weeks
• Progression free survival
Time frame: 48 weeks
• Adverse and serious adverse events (as defined in GCP)
Time frame: 48 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Oct 2021.
- Background: PubMed 20551155Tyndall AJ, Bannert B, Vonk M, Airo P, Cozzi F, Carreira PE, Bancel DF, Allanore Y, Muller-Ladner U, Distler O, Iannone F, Pellerito R, Pileckyte M, Miniati I, Ananieva L, Gurman AB, Damjanov N, Mueller A, Valentini G, Riemekasten G, Tikly M, Hummers L, Henriques MJ, Caramaschi P, Scheja A, Rozman B, Ton E, Kumanovics G, Coleiro B, Feierl E, Szucs G, Von Muhlen CA, Riccieri V, Novak S, Chizzolini C, Kotulska A, Denton C, Coelho PC, Kotter I, Simsek I, de la Pena Lefebvre PG, Hachulla E, Seibold JR, Rednic S, Stork J, Morovic-Vergles J, Walker UA. Causes and risk factors for death in systemic sclerosis: a study from the EULAR Scleroderma Trials and Research (EUSTAR) database. Ann Rheum Dis. 2010 Oct;69(10):1809-15. doi: 10.1136/ard.2009.114264. Epub 2010 Jun 15.
- Background: PubMed 17133610Hoyles RK, Ellis RW, Wellsbury J, Lees B, Newlands P, Goh NS, Roberts C, Desai S, Herrick AL, McHugh NJ, Foley NM, Pearson SB, Emery P, Veale DJ, Denton CP, Wells AU, Black CM, du Bois RM. A multicenter, prospective, randomized, double-blind, placebo-controlled trial of corticosteroids and intravenous cyclophosphamide followed by oral azathioprine for the treatment of pulmonary fibrosis in scleroderma. Arthritis Rheum. 2006 Dec;54(12):3962-70. doi: 10.1002/art.22204.
- Background: PubMed 22282550Keir GJ, Maher TM, Hansell DM, Denton CP, Ong VH, Singh S, Wells AU, Renzoni EA. Severe interstitial lung disease in connective tissue disease: rituximab as rescue therapy. Eur Respir J. 2012 Sep;40(3):641-8. doi: 10.1183/09031936.00163911. Epub 2012 Jan 26.
- Background: PubMed 18369202Goh NS, Desai SR, Veeraraghavan S, Hansell DM, Copley SJ, Maher TM, Corte TJ, Sander CR, Ratoff J, Devaraj A, Bozovic G, Denton CP, Black CM, du Bois RM, Wells AU. Interstitial lung disease in systemic sclerosis: a simple staging system. Am J Respir Crit Care Med. 2008 Jun 1;177(11):1248-54. doi: 10.1164/rccm.200706-877OC. Epub 2008 Mar 27.
- Derived from this study: PubMed 36375479Maher TM, Tudor VA, Saunders P, Gibbons MA, Fletcher SV, Denton CP, Hoyles RK, Parfrey H, Renzoni EA, Kokosi M, Wells AU, Ashby D, Szigeti M, Molyneaux PL; RECITAL Investigators. Rituximab versus intravenous cyclophosphamide in patients with connective tissue disease-associated interstitial lung disease in the UK (RECITAL): a double-blind, double-dummy, randomised, controlled, phase 2b trial. Lancet Respir Med. 2023 Jan;11(1):45-54. doi: 10.1016/S2213-2600(22)00359-9. Epub 2022 Nov 11.
- Derived from this study: PubMed 28619061Saunders P, Tsipouri V, Keir GJ, Ashby D, Flather MD, Parfrey H, Babalis D, Renzoni EA, Denton CP, Wells AU, Maher TM. Rituximab versus cyclophosphamide for the treatment of connective tissue disease-associated interstitial lung disease (RECITAL): study protocol for a randomised controlled trial. Trials. 2017 Jun 15;18(1):275. doi: 10.1186/s13063-017-2016-2.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Toby M Maher, MD PhD study chair
Royal Brompton and Harefield Foundation NHS Trust
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Rituximab and Cyclophosphamide in people with Interstitial Lung Disease and Scleroderma, run by Royal Brompton & Harefield NHS Foundation Trust at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 7 Oct 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Absolute change in FVC (time frame: 48 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01862926, which also lists 6 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Oct 2021.