title: Treating idiopathic pulmonary fibrosis with the addition of co-trimoxazole: a randomised controlled trial.
abstract: 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. ISRCTN22201583.
authors.affiliation: Norwich Medical School, University of East Anglia, Norwich, UK.
authors.forename: Ludmila
authors.initials: L
authors.lastname: Shulgina
authors.forename: Anthony P
authors.initials: AP
authors.lastname: Cahn
authors.forename: Edwin R
authors.initials: ER
authors.lastname: Chilvers
authors.forename: Helen
authors.initials: H
authors.lastname: Parfrey
authors.forename: Allan B
authors.initials: AB
authors.lastname: Clark
authors.forename: Edward C F
authors.initials: EC
authors.lastname: Wilson
authors.forename: Orion P
authors.initials: OP
authors.lastname: Twentyman
authors.forename: Anthony G
authors.initials: AG
authors.lastname: Davison
authors.forename: John J
authors.initials: JJ
authors.lastname: Curtin
authors.forename: Michael B
authors.initials: MB
authors.lastname: Crawford
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Wilson
mesh_terms: D000368:Aged; D000890:Anti-Infective Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D054990:Idiopathic Pulmonary Fibrosis / Q000188:drug therapy* / Q000401:mortality / Q000503:physiopathology; D057194:Intention to Treat Analysis; D008297:Male; D008875:Middle Aged; D011788:Quality of Life; D012129:Respiratory Function Tests; D016896:Treatment Outcome; D015662:Trimethoprim, Sulfamethoxazole Drug Combination / Q000627:therapeutic use*
chemical_list: D000890:Anti-Infective Agents; D015662:Trimethoprim, Sulfamethoxazole Drug Combination