Plain English Summary
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@esth.nhs.uk
Trial website
Contact information
Type
Scientific
Primary contact
Dr Veronica Varney
ORCID ID
Contact details
St Helier Hospital
Wrythe lane
Carshalton
surrey
SM51AA
United Kingdom
+44 (0)20 8296 2401
veronica.varney@esth.nhs.uk
Additional identifiers
EudraCT number
ClinicalTrials.gov number
Protocol/serial number
06-09-2006-0208-296-2401
Study information
Scientific title
A double-blind, randomised, placebo-controlled study of co-trimoxazole in advanced pulmonary fibrosis
Acronym
Study hypothesis
Cotrimoxazole may have therapeutic benefit pulmonary fibrosis (both UIP/IPF and Fibrotic NSIP)
Ethics approval
South East Research Ethics Committee, 15/08/2007, ref: 07/MRE01/36
Study design
Double-blind randomised placebo-controlled trial
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Trial setting
Hospitals
Trial type
Treatment
Patient information sheet
Not available in web format, please use the contact details below to request a patient information sheet
Condition
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
Phase
Not Applicable
Drug names
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 trial start date
01/09/2012
Overall trial end date
01/10/2021
Reason abandoned (if study stopped)
Eligibility
Participant 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
Participant type
Patient
Age group
Adult
Gender
Both
Target number of participants
140
Participant 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
Recruitment start date
06/10/2012
Recruitment end date
06/10/2020
Locations
Countries of recruitment
United Kingdom
Trial participating centre
St Helier Hospital
surrey
SM51AA
United Kingdom
Sponsor information
Organisation
St Helier Hospital (UK)
Sponsor details
Wrythe Lane
Carshalton
Surrey
SM5 1AA
United Kingdom
+44 (0)20 8296 2848
yvonne.reilly@esth.nhs.uk
Sponsor type
Hospital/treatment centre
Website
Funders
Funder type
Charity
Funder name
Peel Medical Trust Fund (UK)
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Funder name
Rotary Club Banstead, Surrey (UK)
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Funder name
Morriston Davies Joint Fellowship (UK)
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Results and Publications
Publication and dissemination plan
IPD sharing statement
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).
Intention to publish date
Participant level data
Other
Basic results (scientific)
Publication list