Treating idiopathic pulmonary fibrosis with the addition of co-trimoxazole: a randomised controlled trial
- Ludmila Shulgina1,
- Anthony P Cahn2,
- Edwin R Chilvers3,
- Helen Parfrey3,
- Allan B Clark1,
- Edward C F Wilson1,
- Orion P Twentyman4,
- Anthony G Davison5,
- John J Curtin4,
- Michael B Crawford4,
- Andrew M Wilson1,4
- 1Norwich Medical School, University of East Anglia, Norwich, UK
- 2Department of Respiratory Medicine, Bedford Hospital NHS Trust, Bedford, UK
- 3Respiratory Medicine Division, Department of Medicine, School of Clinical Medicine, University of Cambridge, CUHNHSFT and Papworth Hospitals, Cambridge, UK
- 4Department of Respiratory Medicine, Norfolk and Norwich University Hospital NHS Foundation Trust, Norwich, UK
- 5Department of Respiratory Medicine, Southend University Hospital NHS Foundation Trust, Essex, UK
- Correspondence to Dr Andrew M Wilson, Norwich Medical School, University of East Anglia, Norwich, Norfolk NR4 7TJ, UK;
- Received 10 July 2012
- Revised 14 October 2012
- Accepted 18 October 2012
- Published Online First 10 November 2012
Background Idiopathic pulmonary fibrosis (IPF) is a fatal condition with limited treatment options. However, in a previous small study, co-trimoxazole was found to be beneficial.
Methods In a double-blind multicentre study, 181 patients with fibrotic idiopathic interstitial pneumonia (89% diagnosed as definite/probable IPF) were randomised to receive co-trimoxazole 960 mg twice daily or placebo for 12 months in addition to usual care. Measurements were made of forced vital capacity (FVC) (primary endpoint), diffusing capacity of carbon monoxide (Dlco) and EuroQol (EQ5D)-based utility, 6-minute walk test (6MWT) and Medical Research Council (MRC) dyspnoea score (secondary endpoints). All-cause mortality and adverse events were recorded (tertiary endpoints).
Results Co-trimoxazole had no effect on FVC (mean difference 15.5 ml (95% CI −93.6 to 124.6)), Dlco (mean difference −0.12 mmol/min/kPa (95% CI 0.41 to 0.17)), 6MWT or MRC dyspnoea score (intention-to-treat analysis). The findings of the per-protocol analysis were the same except that co-trimoxazole treatment resulted in a significant improvement in EQ5D-based utility (mean difference 0.12 (95% CI 0.01 to 0.22)), a reduction in the percentage of patients requiring an increase in oxygen therapy (OR 0.05 (95% CI 0.00 to 0.61)) and a significant reduction in all-cause mortality (co-trimoxazole 3/53, placebo 14/65, HR 0.21 (95% CI 0.06 to 0.78), p=0.02)) compared with placebo. The use of co-trimoxazole reduced respiratory tract infections but increased the incidence of nausea and rash.
Conclusions The addition of co-trimoxazole therapy to standard treatment for fibrotic idiopathic interstitial pneumonia had no effect on lung function but resulted in improved quality of life and a reduction in mortality in those adhering to treatment.