Oral co-trimoxazole fails to reduce adverse outcomes in patients with IPF

Treatment with oral co-trimoxazole did not reduce time to death, lung transplant or nonelective hospitalization compared with placebo in patients with moderate or severe idiopathic pulmonary fibrosis in the EME-TIPAC trial.

Researchers conducted a double-blind, placebo-controlled, parallel, randomized trial to evaluate the efficacy of co-trimoxazole in patients with moderate and severe IPF. Co-trimoxazole (trimethoprim-sulfamethoxazole) is a broad-spectrum antibiotic that was associated with benefit in previous studies.

The EME-TIPAC trial included 342 patients with moderate to severe IPF, breathlessness and impaired lung function treated at 39 U.K. specialist interstitial lung disease centers from April 2015 to April 2019. Patients were randomly assigned to 960 mg co-trimoxazole twice per day (n = 170; mean age, 71.9 years; 81.7% men) or placebo (n = 172; mean age, 70.7 years; 91.3% men) for 12 to 42 months. Patients in both groups also received 5 mg folic acid once per day.

Eighty-three percent of patients completed the trial, with a mean duration of follow-up of 1.02 years.

The primary outcome was time to death, lung transplant or first nonelective hospital admission. Secondary outcomes included individual components of respiratory-related events, lung function and patient-reported outcomes.

Number of events per person-year of follow-up was 0.45 among patients assigned co-trimoxazole and 0.38 among those assigned placebo (HR = 1.2; 95% CI, 0.9-1.6; P = .32), according to the results.

The researchers reported no significant differences in other event outcomes, lung function or patient-reported outcomes.

“In contrast to the previous smaller study that compared co-trimoxazole with placebo in patients with IPF, there was no reduction in mortality with co-trimoxazole,” Andrew M. Wilson, MD, clinical senior lecturer in respiratory health at the University of East Anglia and honorary consultant physician in respiratory medicine at Norfolk and Norwich University Hospital, Norwich, U.K., and colleagues wrote in JAMA.

Results showed a significant difference in cough severity score in favor of co-trimoxazole, but the researchers noted that “given the null primary outcome results and large number of secondary outcomes, the findings for cough should be considered only hypothesis-generating.”

There were 696 adverse events in the co-trimoxazole group compared with 640 in the placebo group. The most commonly reported adverse events for patients in the co-trimoxazole group and placebo group included nausea (89 events and 67 events, respectively), diarrhea (52 and 84, respectively), vomiting (28 and 20, respectively) and rash (31 and 20, respectively).