Clinical Question

Do prophylactic antibiotics improve outcomes in adults with idiopathic pulmonary fibrosis (IPF)?

Bottom Line

The study found an increased number of adverse events without any significant benefit from antimicrobial therapy compared with usual care alone for adults with IPF. The study was terminated earlier than planned because of futility and the possibility of significantly increased harm. (Level of Evidence = 1b)

Synopsis

An increased lung bacterial load is associated with disease progression in adults with IPF. The investigators randomized (concealed allocation assignment) 513 adults, 18 years or older, who met the standard diagnostic criteria for IPF to receive antimicrobial therapy (trimethoprim, 160 mg/sulfamethoxazole, 800 mg twice daily, plus folic acid, 5 mg daily, or doxycycline, 100 mg once or twice daily, depending on body weight) in addition to usual care or to usual care alone (no placebo was provided). Although patients and their clinicians remained aware of their treatment group assignment, the individuals who assessed outcomes were unaware of the assignments. Complete follow-up occurred for more than 97% of participants for a median of 12.7 months. Using intention-to-treat analysis, no differences occurred between the antimicrobial group and the usual care alone group for the primary end point of respiratory event–related hospitalization or all-cause mortality. No significant treatment group differences occurred in multiple secondary outcomes, including respiratory infections, fatigue, or quality of life. An increased number of adverse events occurred in the antimicrobial groups, including diarrhea, rash, vomiting, and arrhythmias secondary to hyperkalemia.

Study design: Randomized controlled trial (single-blinded)

Funding source: Foundation

Allocation: Concealed

Setting: Outpatient (specialty)

Reference: Martinez FJ, Yow E, Flaherty K, R, et al.; CleanUP-IPF Investigators of the Pulmonary Trials Cooperative. Effect of antimicrobial therapy on respiratory hospitalization or death in adults with idiopathic pulmonary fibrosis: the CleanUP-IPF randomized clinical trial. JAMA. 2021;325(18):1841–1851.