Study of co-trimoxazole in advanced pulmonary fibrosis
| ISRCTN | ISRCTN87032740 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN87032740 |
| EudraCT/CTIS number | 2006-004927-12 |
| Secondary identifying numbers | 06-09-2006-0208-296-2401 |
- Submission date
- 20/08/2012
- Registration date
- 09/10/2012
- Last edited
- 01/11/2021
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Respiratory
Plain English summary of protocol
Background and study aims
Pulmonary fibrosis is a disease in which scars form in the lung tissues, leading to serious breathing problems such as perpetual shortness of breath. Previous studies have shown clinical improvement in patients treated with the drug co-trimoxazole. The aim of this study is to expand a previous small study to a larger study and confirm whether co-trimoxazole is effective at treating pulmonary fibrosis.
Who can participate?
Patients aged 40 to 86 with pulmonary fibrosis.
What does the study involve?
Participants are randomly allocated to be treated with either co-trimoxazole or an identical placebo (dummy drug) for 12 weeks. Participants are assessed with walking tests, lung function tests, questionnaires and blood tests.
What are the possible benefits and risks of participating?
The risks are minimal and the safety of cotrimoxazole is well established in transplant cases and other immune-suppressed patients, where it is used long-term. The study excludes those allergic to cotrimoxazole (septrin) and requires patients to take folic acid for bone marrow protection. The study is short (12 weeks) and placebo patients can receive active treatment after that so they are not denied active treatment for long.
Where is the study run from?
St Helier Hospital (UK)
When is the study starting and how long is it expected to run for?
September 2012 to October 2021
Who is funding the study?
Peel Medical Trust Fund, Rotary Club and the Morriston-Davies Trust (UK)
Who is the main contact?
Dr Veronica Varney
veronica.varney@nhs.uk
Contact information
Scientific
St Helier Hospital
Wrythe lane
Carshalton
surrey
SM51AA
United Kingdom
| Phone | +44 (0)20 8296 2401 |
|---|---|
| veronica.varney@nhs.uk |
Study information
| Study design | Double-blind randomised placebo-controlled trial |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Hospital |
| Study type | Treatment |
| Participant information sheet | Not available in web format, please use the contact details below to request a patient information sheet |
| Scientific title | A double-blind, randomised, placebo-controlled study of co-trimoxazole in advanced pulmonary fibrosis |
| Study objectives | Cotrimoxazole may have therapeutic benefit pulmonary fibrosis (both UIP/IPF and Fibrotic NSIP) |
| Ethics approval(s) | South East Research Ethics Committee, 15/08/2007, ref: 07/MRE01/36 |
| Health condition(s) or problem(s) studied | Advanced pulmonary fibrosis (UIP/IPF and fibrotic NSIP) |
| Intervention | The study will consist of two phases: 1. Double-blind randomised phase (3 months) 2. Open-label extension phase (to complete 12 months on treatment) |
| Intervention type | Drug |
| Pharmaceutical study type(s) | |
| Phase | Not Applicable |
| Drug / device / biological / vaccine name(s) | Co-trimoxazole |
| Primary outcome measure | Change from baseline to 3 months in forced vital capacity |
| Secondary outcome measures | Change from baseline to 3 months in: 1. Shuttle walking test 2. Symptom score on the MRC 5-Point Dyspnoea Scale. 3. Total lung capacity 4. Pulmonary gas exchange, as measured by DLCO and KCO 5. Cough, as measured by diary cards 6. SGRQ 7. Resting oxygen saturation on air 8. Chest radiograph 9. Changes in pulmonary cytokines relevant to this disease at entry & 3 months A further efficacy endpoint will be a formal assessment of response to therapy (Favourable Response, Stable Response, Failure of Response) as defined in the ATS/ERS International Consensus statement (2000). |
| Overall study start date | 01/09/2012 |
| Completion date | 01/10/2021 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Sex | Both |
| Target number of participants | 140 |
| Key inclusion criteria | 1. Male or female 2. Aged 40 86 years 3. An established clinical history consistent with IIP according to the criteria for diagnosis outlined in the ATS/ERS consensus statement. (Bronchoscopic and/or biopsy data, although desirable, are not required for patient entry into the trial) 4. Clear cut HRCT evidence of UIP or fibrotic NSIP. An HRCT within 6 months of study enrolment is required. Lung function within 3 months of enrolement 5. Permitted concurrent therapies are: 5.1. Prednisolone 1 30 mg per day, established for at least 3 months at study entry 5.2. Short burst oxygen therapy for symptomatic benefit only 6. Stability of the disease process itself following the introduction of prednisolone is not required for study entry 7. Patients in whom oral steroids have been withdrawn due to lack of efficacy are eligible 8. Oxygen desaturation below 90% on a shuttle-walking test 9. MRC score of 3 or more |
| Key exclusion criteria | 1. A secondary cause for pulmonary fibrosis 2. Subject currently smokes 3. A recognized coexisting respiratory disorder (e.g. significant COPD, asthma, sarcoid or lung carcinoma) that in the opinion of the investigator would put the patient at risk or invalidate the study outcome measures 4. A requirement for long-term oxygen therapy (LTOT) at entry as defined by the prescription of oxygen to be used for greater than or equal to 12 hours therapy per day 5. Overt and persistent right heart failure 6. Inability to perform the shuttle walking tests 7. Women who are pregnant, or who have the potential to become pregnant during the course of the study, or who are breast feeding 8. Co-trimoxazole allergy or prior known intolerance 9. Untreated vitamin B12 deficiency 10. Suspected or known glucose-6-phosphate dehydrogenase deficiency 11. Impaired renal function with an established creatinine greater than 175 ìmol/l 12. The following therapies will not be permitted on entry to the study: 12.1. Long-term oxygen therapy (LTOT) 12.2. Azathioprine 12.3 Cyclophosphamide 12.4. Methotrexate 12.5. D-penicillamine 12.6. Colchicine 12.7. Gamma-interferon 13. The following therapies will require caution or increased monitoring: 13.1. Digoxin 13.2 Warfarin 13.3. Phenytoin 13.4. Sulphonylureas 13.5. Procainamide hydrochloride |
| Date of first enrolment | 06/10/2012 |
| Date of final enrolment | 06/10/2020 |
Locations
Countries of recruitment
- England
- United Kingdom
Study participating centre
SM51AA
United Kingdom
Sponsor information
Hospital/treatment centre
Wrythe Lane
Carshalton
Surrey
SM5 1AA
England
United Kingdom
| Phone | +44 (0)20 8296 2848 |
|---|---|
| yvonne.reilly@esth.nhs.uk | |
| Website | http://www.epsom-sthelier.nhs.uk/ |
"ROR" |
https://ror.org/019hb9542 |
Funders
Funder type
Charity
No information available
No information available
No information available
Results and Publications
| Intention to publish date | |
|---|---|
| Individual participant data (IPD) Intention to share | Yes |
| IPD sharing plan summary | Other |
| Publication and dissemination plan | |
| IPD sharing plan | The datasets generated and/or analysed during the current study during this study will be included in the subsequent results publication as it is a double-blind study, although I plan to publish the first 50 cases from their out of study data (treatment out of study in the open part of the study to show how steady the lung function has remained). |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Abstract results | results | 16/11/2016 | 24/01/2020 | No | No |
Editorial Notes
01/11/2021: The following changes were made to the trial record:
1. The contact email was updated.
2. The plain English summary was updated to reflect these changes.
04/02/2020: EudraCT number added.
24/01/2020: Publication reference added.
03/01/2019: The recruitment end date was changed from 01/09/2019 to 06/10/2020.
24/01/2018: Participant level data was added.
18/12/2017: Overall trial date has been updated from 01/09/2019 to 01/10/2021.
08/09/2017: Recruitment start date has been updated from 01/09/2012 to 06/10/2012. Recruitment end date has been updated from 01/09/2016 to 01/09/2019. Overall trial end date has been updated from 01/09/2016 to 01/09/2019.
