Abstract Number: PB0045
Meeting: ISTH 2022 Congress
Theme: COVID and Coagulation » COVID and Coagulation, Clinical
Background: Alveolar fibrin deposition and pulmonary microthrombi are pathophysiological features of COVID-19-induced respiratory failure. Nebulised thrombolysis offers locally targeted therapy with potentially lower bleed risk than systemic administration.
Aims: To investigate the safety and potential for clinical efficacy of nebulised recombinant tissue plasminogen activator (rt-PA) for improving oxygenation in patients hospitalised with COVID-19 complicated by mild to severe acute respiratory distress syndrome (ARDS).
Methods: Patients hospitalised with severe COVID-19 and a PaO2/FiO2 (P/F) ratio of < 300 (units), requiring invasive mechanical ventilation (IMV) or non-invasive respiratory support (NIRS) received 40–60mg per day of rt-PA, dosed for ≤14 days in a phase II, open-label, single-centre pilot study. Efficacy was assessed via improved oxygenation. Safety was assessed by treatment-related serious adverse event bleeding and reduction of fibrinogen to < 1.0–1.5 g/L.
Results: Nine (Cohort 1 [C1]; 6/9 IMV, 3/9 NIRS) and 26 adults (Cohort 2 [C2]; 12/26 IMV, 14/26 NIRS) received nebulised rt-PA alongside standard of care. Matched historical controls (HC) (n=18) were used for comparison in C1. Mean P/F ratio increased in both C1 groups from baseline (BL) to end of study (EOS) (rt-PA; 154.4 to 298.8 vs. HC; 154.1 to 211.6); a linear mixed effect model confirmed higher P/F ratios in the rt-PA group. Among C2 groups, greater improvements in mean P/F ratio from BL to EOS were seen in the NIRS group (NIRS; 125.5 to 239.4 vs. IMV; 120.3 to 188.2). Four potentially treatment-related bleeds were reported; no clinically significant fibrinogen reductions were observed. Lower mortality was observed in the C1 rt-PA group (11.1%) vs. the HC group (55.6%) and in the C2 NIRS group (21.4%) vs. the IMV group (41.7%).
Conclusion(s): Nebulised rt-PA is well-tolerated, improves oxygenation in patients with COVID-19-related ARDS, and merits a randomised controlled trial to confirm efficacy and potentially identify a subgroup of interest.
To cite this abstract in AMA style:
Chowdary P, Agarwal B, Bhagani S, Lipman M, Gomez K. A pilot, open-label, phase II clinical trial of nebulised recombinant tissue-plasminogen activator in patients with COVID-19 acute respiratory distress syndrome: the PACA trial [abstract]. https://abstracts.isth.org/abstract/a-pilot-open-label-phase-ii-clinical-trial-of-nebulised-recombinant-tissue-plasminogen-activator-in-patients-with-covid-19-acute-respiratory-distress-syndrome-the-paca-trial/. Accessed March 21, 2024.« Back to ISTH 2022 Congress
ISTH Congress Abstracts - https://abstracts.isth.org/abstract/a-pilot-open-label-phase-ii-clinical-trial-of-nebulised-recombinant-tissue-plasminogen-activator-in-patients-with-covid-19-acute-respiratory-distress-syndrome-the-paca-trial/