Effect of Intrapleural Fibrinolytic Therapy vs Surgery for Complicated Pleural Infections: A Randomized Clinical Trial.

IMPORTANCE

There is a paucity of high-quality prospective randomized clinical trials comparing intrapleural fibrinolytic therapy (IPFT) with surgical decortication in patients with complicated pleural infections.

OBJECTIVE

To assess the feasibility, safety, and efficacy of an algorithm comparing tissue plasminogen activator plus deoxyribonuclease therapy with surgical decortication in patients with complicated pleural infections.

DESIGN, SETTING, AND PARTICIPANTS: This parallel pilot randomized clinical trial was performed at a single urban community-based center from March 1, 2019, to December 31, 2021, with follow-up for 90 days. Seventy-four individuals were screened and 48 were excluded. Twenty-six patients 18 years or older with clinical pleural infection and positive findings of pleural fluid analysis were included. Of these, 20 patients underwent randomized selection (10 in each group), and 6 were observed.

INTERVENTIONS

Intrapleural tissue plasminogen activator plus deoxyribonuclease therapy vs surgical decortication.

MAIN OUTCOMES AND MEASURES

Primary outcomes were the percentage of patients enrolled to study completion and multidisciplinary adherence. Secondary outcomes included the number of patients with and the reason for inadequate screening, screening to enrollment failures, time to accrual of 20 patients or the number accrued at 1 year, and clinical data.

RESULTS

Twenty-six patients were enrolled, 10 were randomized to each group, and 6 were observed. There was 100% enrollment to study completion in each treatment group, no protocol deviations, 2 minor protocol amendments, and no screening to enrollment failures. It took 32 months to enroll 26 patients. The 20 randomized patients had a median age of 57 (IQR, 46-65) years, were predominantly men (15 [75%]), and had a median RAPID (Renal, Age, Purulence, Infection Source, and Dietary Factors) score of 2 (IQR, 1-3). Treatment failure occurred in 1 patient and 2 crossover treatments occurred, all of which were in the IPFT group. Intraprocedure and postprocedure complications were similar between the groups. There were no reoperations or in-hospital deaths. Median duration of chest tube use was comparable in the IPFT (5 [IQR, 4-8] days) and surgery (4 [IQR, 3-5] days) groups (P = .21). Median hospital stay tended to be longer in the IPFT (11 [IQR, 4-18] days) vs surgery (5 [IQR, 4-6] days) groups, although the difference as not significantly different (P = .08). There were no 30-day readmissions or 30- or 90-day deaths.

CONCLUSIONS AND RELEVANCE

In this pilot randomized clinical trial, the study algorithm was feasible, safe, and efficacious. This provides evidence to move forward with a multicenter randomized clinical trial.

TRIAL REGISTRATION

ClinicalTrials.gov Identifier: NCT03873766.