Fibrinolytic Therapy to Treat ARDS in the Setting of COVID-19 Infection
Summary
The global pandemic COVID-19 has overwhelmed the medical capacity to accommodate a large surge of patients with acute respiratory distress syndrome (ARDS). In the United States, the number of cases of COVID-19 ARDS is projected to exceed the number of available ventilators. Reports from China and Italy indicate that 22-64% of critically ill COVID-19 patients with ARDS will die. ARDS currently has no evidence-based treatments other than low tidal ventilation to limit mechanical stress on the lung and prone positioning. A new therapeutic approach capable of rapidly treating and attenuating ARDS secondary to COVID-19 is urgently needed. The dominant pathologic feature of viral-induced ARDS is fibrin accumulation in the microvasculature and airspaces. Substantial preclinical work suggests antifibrinolytic therapy attenuates infection provoked ARDS. In 2001, a phase I trial 7 demonstrated the urokinase and streptokinase were effective in patients with terminal ARDS, markedly improving oxygen delivery and reducing an expected mortality in that specific patient cohort from 100% to 70%. A more contemporary approach to thrombolytic therapy is tissue plasminogen activator (tPA) due to its higher efficacy of clot lysis with comparable bleeding risk 8. We therefore propose a phase IIa clinical trial with two intravenous (IV) tPA treatment arms and a control arm to test the efficacy and safety of IV tPA in improving respiratory function and oxygenation, and consequently, successful extubation, duration of mechanical ventilation and survival.
Timeline
- Start
- 2020-05-14
- Primary completion
- 2021-03-21
- Completion
- 2021-09-30
Publications
- Barrett CD, Moore HB, Moore EE, Wang J, Hajizadeh N, Biffl WL, Lottenberg L, Patel PR, Truitt MS, McIntyre RC Jr, Bull TM, Ammons LA, Ghasabyan A, Chandler J, Douglas IS, Schmidt EP, Moore PK, Wright FL, Ramdeo R, Borrego R, Rueda M, Dhupa A, McCaul DS, Dandan T, Sarkar PK, Khan B, Sreevidya C, McDaniel C, Grossman Verner HM, Pearcy C, Anez-Bustillos L, Baedorf-Kassis EN, Jhunjhunwala R, Shaefi S, Capers K, Banner-Goodspeed V, Talmor DS, Sauaia A, Yaffe MB. Study of Alteplase for Respiratory Failure in SARS-CoV-2 COVID-19: A Vanguard Multicenter, Rapidly Adaptive, Pragmatic, Randomized Controlled Trial. Chest. 2022 Mar;161(3):710-727. doi: 10.1016/j.chest.2021.09.024. Epub 2021 Sep 27.
- Moore HB, Barrett CD, Moore EE, Jhunjhunwala R, McIntyre RC, Moore PK, Wang J, Hajizadeh N, Talmor DS, Sauaia A, Yaffe MB. Study of alteplase for respiratory failure in severe acute respiratory syndrome coronavirus 2/COVID-19: Study design of the phase IIa STARS trial. Res Pract Thromb Haemost. 2020 Aug 19;4(6):984-996. doi: 10.1002/rth2.12395. eCollection 2020 Aug.