Efficacy and Safety of Combined Autologous Blood Patch and Doxycycline Pleurodesis for the Management of Persistent Air Leaks in Secondary Spontaneous Pneumothorax: A Randomized Controlled Trial

Abstract

Background: Persistent air leak (PAL) is a frequent and challenging complication of secondary spontaneous pneumothorax (SSP) and often prolongs hospitalization. We compared the efficacy and safety of autologous blood patch pleurodesis (ABPP) plus doxycycline with those of ABPP alone for managing PAL in patients with SSP who were considered unfit for surgery. Methods: This prospective, randomized controlled trial enrolled 121 patients with SSP and PAL lasting ≥7 days. Participants were randomized to receive ABPP alone (n=62) or ABPP plus intrapleural doxycycline (n=59). The primary outcome was time to air leak cessation. Secondary outcomes included the 7-day success rate, time to drain removal, length of hospital stay, pain score, complications, and recurrence at 1 and 3 months. Results: Kaplan-Meier analysis showed significantly faster air leak cessation in the ABPP plus doxycycline group than in the ABPP-alone group (median, 4 days vs. 6 days; log-rank p<0.001). This was accompanied by earlier intercostal drain removal (median, 5 days vs. 7 days; p<0.001) and a shorter hospital stay (median, 12 days vs. 14 days; p<0.001). The 7-day success rate was 81% in the combination group and 74% in the ABPP group (p=0.34). Post-procedural pain scores were higher in the combination group (p<0.001). However, overall complication rates (36% vs. 40%, p=0.6) and 3-month recurrence rates (3.8% vs. 7%, p=0.68) were statistically comparable between groups. Conclusion: Combining doxycycline with ABPP appears to be a safe and effective bedside intervention. Compared with ABPP alone, the combination significantly accelerated air leak cessation and shortened hospitalization, while achieving pleural symphysis without increasing major complications (trial registration number: Pan African Clinical Trials Registry, PACTR202505753650802).