Contact information
Type
Scientific
Primary contact
Dr Veronica Varney
ORCID ID
Contact details
St Helier Hospital
Wrythe Lane
Carshalton
SM5 1AA
United Kingdom
+44 (0)20 8296 2401
vvarney@epsom-sthelier.nhs.uk
Additional identifiers
EudraCT number
ClinicalTrials.gov number
Protocol/serial number
UK study number for local regional ethical committee (LREC) 64/99
Study information
Scientific title
Double Blind Randomised Placebo Controlled Trial of Oral Co-trimoxazole in Pulmonary Fibrosis
Acronym
Septrin and CFA
Study hypothesis
Oral Co-trimoxazole improves exercise capacity in patients with pulmonary fibrosis
Ethics approval
Not provided at time of registration
Study design
Randomised controlled trial
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Trial setting
Not specified
Trial type
Treatment
Patient information sheet
Condition
Idiopathic pulmonary fibrosis (UIP/NSIP/Mixed)
Intervention
Investigations prior to selection and randomisation:
All selected patients underwent baseline investigations before entry. This included:
1. Arterial gases at rest (on air)
2. Pulmonary function tests (laboratory measurement of TLC, DLCO)
3. St Georges Hospital respiratory questionnaire (SGHRQ), and MRC 5 Point Dyspnoea Score
4. Two shuttle-walking tests (2 weeks apart) demonstrating oxygen desaturation below 90% (either during or upon cessation of exercise)
5. An echocardiogram and ECG
6. Routine bloods tests including serum samples for cytokine measurements
7. Sputum samples for pneumocystis silver stain at request of Ethics Committee
Randomisation:
Patients were randomly allocated to active or placebo treatments by our clinical trials pharmacist, using computer generated random numbers. This assigned patients to study treatment groups, with a patient number. The study was conducted double blind. To preserve the double blind status of the trial, medication was issued by the pharmacist; using identical placebo tablets and labelling to ensure all treatment packs were identical.
Drug Treatment:
Co-trimoxazole or identical placebo (480 mg) tablets were supplied with dosage according to body-weight. Patients up to 70 kg received 960 mg bd, those above 70 kg, took 1440 mg (3 x 480 mg) bd. Folic acid 5 mg was given 3 times a week (minimum dose) to protect the bone marrow. Ranitidine 150 mg bd was supplied but optional for any indigestion. Patients on oral daily prednisolone had no adjustments to their prednisolone dose throughout the double blind study, except that permitted during a viral illness.
Assessment during Study:
On entry to the study all patients made visits for the following assessments every 2 weeks:
1. Body-weight
2. Resting respiratory rate and chest auscultation
3. FVC
4. Oxygen saturations at rest and during shuttle walking test and recovery recorded by Pulsox 3i wrist watch Minolta range
5. MRC-5 Point Dyspnoea Score
6. Compliance with treatment/side effects/study withdrawal and deaths were assessed and recorded
7. Blood tests (FBC, U & E, LFTs, ESR and CRP)
At 3 months all patients had arterial gases, full pulmonary function tests, serum cytokines and SGHRQ, repeated. Six weeks of pulmonary rehabilitation (rehab) was then commenced. Two weeks post rehabilitation final assessments were made before decoding. These assessments were identical to the regular 2 week assessments during the study.
Intervention type
Drug
Phase
Not Specified
Drug names
Co-trimoxazole
Primary outcome measure
Exercise capacity (shuttle walking test) with area under the curve oxygen desaturation
Secondary outcome measures
1. Respiratory function tests (FVC, TLC, DLCO)
2. Arterial oxygen measurements
3. Quality of life data
4. Benefit of pulmonary rehabilitation
Twenty patients were selected.
Overall trial start date
21/02/2000
Overall trial end date
01/02/2004
Reason abandoned (if study stopped)
Eligibility
Participant inclusion criteria
1. Male or female below 85 years old
2. Demonstrated breathlessness with oxygen desaturation below 90% on two baseline shuttle walking tests (SWT)
3. Physical examination, HRCT scan and pulmonary function test results compatible with IPF (with or without histological diagnosis)
4. New diagnosis of IPF without treatment or previous diagnosis on regular daily prednisolone
5. Symptoms of exertional dyspnoea affecting life quality
6. Normal glucose 6-phosphate dehydrogenase levels to avoid drug induced haemolysis. Normal vitamin B12 levels
Participant type
Patient
Age group
Adult
Gender
Both
Target number of participants
20
Participant exclusion criteria
1. Recognised secondary causes of pulmonary fibrosis
2. Co-trimoxazole allergy or severe upper GI symptoms
3. Abnormal liver function tests or concurrent drug treatments that disturb liver function including azathioprine
4. Inability to perform the shuttle test due to musculoskeletal or cardiac causes
Recruitment start date
21/02/2000
Recruitment end date
01/02/2004
Locations
Countries of recruitment
United Kingdom
Trial participating centre
St Helier Hospital
Carshalton
SM5 1AA
United Kingdom
Funders
Funder type
Charity
Funder name
Part funded by The Peel Trust Fund for funding of placebo and Co-trimoxazole drugs only
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
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
Basic results (scientific)
Publication list
2008 results in https://www.ncbi.nlm.nih.gov/pubmed/17500020