Procalcitonin-guided use of antibiotic in hospitalized patients with acute exacerbation of chronic obstructive pulmonary disease: a randomized clinical trial.

Objectives: The objectives of this study are to analyse the effect and safety of procalcitonin (PCT)-guided antibiotic therapy in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD).

Methods: We conducted a multicentre, open-label, randomized controlled trial amongst patients hospitalized for AECOPD in six hospitals in China. Enrolled patients were randomly assigned to either the PCT-guided group or the Global Initiative for Chronic Obstructive Lung Disease (GOLD) strategy-guided group. The co-primary endpoints were antibiotic prescription rate for AECOPD within 30 days after randomization (to demonstrate superiority) and treatment success rate at day 30 after randomization (to demonstrate non-inferiority). For primary outcomes, χ² test, corrected χ² test, or Fisher's exact test was used to evaluate the differences between the intervention and control groups. 95% CIs were calculated for all the outcomes. Secondary outcomes, including days of antibiotic use during hospitalization, length of hospital stay, and change in modified Medical Research Council dyspnoea scale and COPD Assessment Test score, were compared using the Student's t-test, with corresponding differences and 95% CIs calculated. Intention-to-treat (ITT) population were those who were randomly assigned, and per-protocol population were those who strictly adhered to the treatment plan.

Results: A total of 455 patients were randomly assigned, with 229 in the PCT-guided group and 226 in the GOLD-guided group. The rate of antibiotic prescription for AECOPD by day 30 was significantly lower in the PCT-guided group than that in the GOLD-guided group (38% [88/229] vs. 59% [134/226]; difference -21%; 95% CI: -30% to -12%; p < 0.0001) in the ITT analysis. There was no significant difference in the clinical treatment success rate by day 30 between the 2 groups (97% [223/229] vs. 94% [212/229]; difference 4%, 95% CI: 0-7%; p 0.06). Compared with the GOLD strategy, PCT-guided antibiotic therapy was significantly associated with lower antibiotic prescription rate during hospitalization (37% vs. 59%, difference -22%, 95% CI: -31 to -13; p < 0.0001), and fewer days of antibiotic use during hospitalization (2.63 ± 4.66 vs. 4.86 ± 4.83, difference -2.23 days, 95% CI: -1.35 to -3.11; p < 0.0001). There were no significant differences between the two groups in length of hospital stay, subsequent exacerbation rate, hospital readmission rate, intensive care unit admission, and 30-day mortality in the ITT analysis. The results in the per-protocol analysis were consistent with that in the ITT analysis.

Discussion: Compared with the GOLD strategy, PCT-guided antibiotic therapy significantly reduced the rate of antibiotic prescription for patients with AECOPD, without negatively affecting the treatment success rate.