Treating pulmonary fibrosis with co-trimoxazole

Not Applicable

Completed

• Conditions: Topic: Respiratory disorders; Subtopic: Respiratory (all Subtopics); Disease: Respiratory; Respiratory

• Registration Number: ISRCTN17464641
• Lead Sponsor: orfolk and Norwich University Hospital NHS Trust

Brief Summary

2018 protocol in https://www.ncbi.nlm.nih.gov/pubmed/29402332 2020 results in https://pubmed.ncbi.nlm.nih.gov/33289822/ (added 10/12/2020)

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2015-01-29
• Study Completion: 2019-05-31
• Last Update Posted: 5 January 2021

Recruitment & Eligibility

• Status: Completed
• Sex: All
• Target Recruitment: 342

Inclusion Criteria

Inclusion criteria as of 21/11/2016:
1. Male or female, aged greater than or equal to 40 years. IPF rarely occurs in individuals less than 40 years. Individuals younger than this more frequently have connective tissue related lung disease which is similar to but different from IPF.
2. A diagnosis of idiopathic pulmonary fibrosis (IPF) based on multi-disciplinary consensus according to the latest international guidelines.
3. Patients may receive oral prednisolone up to a dose of 10 mg per day, anti-oxidant therapy, pirfenidone or other licensed medication for IPF e.g. nintedanib. Patients should be on a stable treatment regimen for at least 4 weeks to ensure baseline values are representative.
4. MRC dyspnoea score of greater than 1.
5. Able to provide informed consent.; Target Gender: Male & Female ; Lower Age Limit 40 years

Original inclusion criteria:
1. Male or female, aged greater than or equal to 40 years. IPF rarely occurs in individuals less than 40 years. Individuals younger than this more frequently have connective tissue related lung disease which is similar to but different from IPF.
2. A diagnosis of idiopathic pulmonary fibrosis (IPF) based on multi-disciplinary consensus according to the latest international guidelines within 2 years of enrollment into the study. Patients with a diagnosis of more than 2 years duration can be enrolled if they have evidence of progressive disease defined as =10% decline in forced vital capacity (FVC) or =15% decline in diffusing capacity of carbon monoxide over the preceding 6 or 12 months.
3. Patients may receive oral prednisolone up to a dose of 10 mg per day, anti-oxidant therapy, pirfenidone or other licensed medication for IPF e.g. nintedanib. Patients should be on a stable treatment regimen for at least 6 weeks to ensure baseline values are representative.
4. MRC dyspnoea score of greater than 1.
5. Able to provide informed consent.; Target Gender: Male & Female ; Lower Age Limit 40 years

Exclusion Criteria

Exclusion criteria as of 21/11/2016:
1. FVC > 75% predicted.
2. A recognised significant co-existing respiratory disease, defined as a respiratory condition that exhibits a greater clinical effect on respiratory symptoms and disease progression than IPF as determined by the principal investigator.
3. Patients with airways disease defined as forced expiratory volume in 1 second (FEV1)/FVC<60%
4. A self-reported respiratory tract infection within 4 weeks of screening defined as two or more of cough, sputum or breathlessness and requiring antimicrobial therapy.
5. Significant medical, surgical or psychiatric disease that in the opinion of the patient’s attending physician would affect subject safety or influence the study outcome including liver (Serum transaminase > 3 x upper limit of normal (ULN), Bilirubin > 2 x ULN) and renal failure (creatinine clearance <30ml/min).
6. Patients receiving recognised immunosuppressant medication (except prednisolone above) including azathioprine and mycophenolate mofetil.
7. Female subjects must be of non-childbearing potential, defined as follows: postmenopausal females who have had at least 12 months of spontaneous amenorrhoea or 6 months of spontaneous amenorrhoea with serum FSH>40mIU/ml or females who have had a hysterectomy or bilateral oophorectomy at least 6 weeks prior to enrolment.
8. Allergy or intolerance to trimethoprim or sulphonamides or their combination.
9. Untreated folate or B12 deficiency.
10. Known glucose-6-phosphate dehydrogenase (G6PD) deficiency or G6PD deficiency measured at screening in males of African, Asian or Mediterranean descent.
11. Receipt of an investigational drug or biological agent within the 4 weeks prior to study entry or 5 times the half-life if longer.
12. Receipt of short course antibiotic therapy for respiratory and other infections within 4 weeks of screening.
13. Patients receiving long term (defined as >1 month of therapy) prophylactic antibiotic treatment will not be eligible as this may have an impact on lung microbiota. Such patients may enrol in the EME-TIPAC trial, if this is supported by their clinician, after a ‘wash-out period’ of 3 months.
14. Serum Potassium greater than 5.0 mmol/l due to the potentially increased risk of hyperkalaemia in patients taking co-trimoxazole in combination with potassium sparing diuretics (including angiotensin converting enzyme inhibitors or angiotensin receptor blockers)

Original exclusion criteria:
1. FVC > 70% predicted.
2. A recognised significant co-existing respiratory disease, defined as a respiratory condition that exhibits a greater clinical effect on respiratory symptoms and disease progression than IPF as determined by the principal investigator.
3. Patients with airways disease defined as forced expiratory volume in 1 second (FEV1)/FVC<60%
4. A self-reported respiratory tract infection within 4 weeks of screening defined as two or more of cough, sputum or breathlessness and requiring antimicrobial therapy.
5. Significant medical, surgical or psychiatric disease that in the opinion of the patient’s attending physician would affect subject safety or influence the study outcome

Study & Design

• Study Type: Interventional
• Study Design: Not specified