Dataset Information

Study of Alteplase for Respiratory Failure in SARS-CoV-2 COVID-19: A Vanguard Multicenter, Rapidly Adaptive, Pragmatic, Randomized Controlled Trial.

ABSTRACT:

Background

Pulmonary vascular microthrombi are a proposed mechanism of COVID-19 respiratory failure. We hypothesized that early administration of tissue plasminogen activator (tPA) followed by therapeutic heparin would improve pulmonary function in these patients.

Research question

Does tPA improve pulmonary function in severe COVID-19 respiratory failure, and is it safe?

Study design and methods

Adults with COVID-19-induced respiratory failure were randomized from May14, 2020 through March 3, 2021, in two phases. Phase 1 (n = 36) comprised a control group (standard-of-care treatment) vs a tPA bolus (50-mg tPA IV bolus followed by 7 days of heparin; goal activated partial thromboplastin time [aPTT], 60-80 s) group. Phase 2 (n = 14) comprised a control group vs a tPA drip (50-mg tPA IV bolus, followed by tPA drip 2 mg/h plus heparin 500 units/h over 24 h, then heparin to maintain aPTT of 60-80 s for 7 days) group. Patients were excluded from enrollment if they had not undergone a neurologic examination or cross-sectional brain imaging within the previous 4.5 h to rule out stroke and potential for hemorrhagic conversion. The primary outcome was Pao₂ to Fio₂ ratio improvement from baseline at 48 h after randomization. Secondary outcomes included Pao₂ to Fio₂ ratio improvement of > 50% or Pao₂ to Fio₂ ratio of ≥ 200 at 48 h (composite outcome), ventilator-free days (VFD), and mortality.

Results

Fifty patients were randomized: 17 in the control group and 19 in the tPA bolus group in phase 1 and eight in the control group and six in the tPA drip group in phase 2. No severe bleeding events occurred. In the tPA bolus group, the Pao₂ to Fio₂ ratio values were significantly (P < .017) higher than baseline at 6 through 168 h after randomization; the control group showed no significant improvements. Among patients receiving a tPA bolus, the percent change of Pao₂ to Fio₂ ratio at 48 h (16.9% control [interquartile range (IQR), -8.3% to 36.8%] vs 29.8% tPA bolus [IQR, 4.5%-88.7%]; P = .11), the composite outcome (11.8% vs 47.4%; P = .03), VFD (0.0 [IQR, 0.0-9.0] vs 12.0 [IQR, 0.0-19.0]; P = .11), and in-hospital mortality (41.2% vs 21.1%; P = .19) did not reach statistically significant differences when compared with those of control participants. The patients who received a tPA drip did not experience benefit.

Interpretation

The combination of tPA bolus plus heparin is safe in severe COVID-19 respiratory failure. A phase 3 study is warranted given the improvements in oxygenation and promising observations in VFD and mortality.

Trial registry

ClinicalTrials.gov; No.: NCT04357730; URL: www.

Clinicaltrials

gov.

SUBMITTER: Barrett CD

PROVIDER: S-EPMC8474873 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature

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Publications

Study of Alteplase for Respiratory Failure in SARS-CoV-2 COVID-19: A Vanguard Multicenter, Rapidly Adaptive, Pragmatic, Randomized Controlled Trial.

Barrett Christopher D CD Moore Hunter B HB Moore Ernest E EE Wang Janice J Hajizadeh Negin N Biffl Walter L WL Lottenberg Lawrence L Patel Purvesh R PR Truitt Michael S MS McIntyre Robert C RC Bull Todd M TM Ammons Lee Anne LA Ghasabyan Arsen A Chandler James J Douglas Ivor S IS Schmidt Eric P EP Moore Peter K PK Wright Franklin L FL Ramdeo Ramona R Borrego Robert R Rueda Mario M Dhupa Achal A McCaul D Scott DS Dandan Tala T Sarkar Pralay K PK Khan Benazir B Sreevidya Coimbatore C McDaniel Conner C Grossman Verner Heather M HM Pearcy Christopher C Anez-Bustillos Lorenzo L Baedorf-Kassis Elias N EN Jhunjhunwala Rashi R Shaefi Shahzad S Capers Krystal K Banner-Goodspeed Valerie V Talmor Daniel S DS Sauaia Angela A Yaffe Michael B MB

Chest 20210927 3

<h4>Background</h4>Pulmonary vascular microthrombi are a proposed mechanism of COVID-19 respiratory failure. We hypothesized that early administration of tissue plasminogen activator (tPA) followed by therapeutic heparin would improve pulmonary function in these patients.<h4>Research question</h4>Does tPA improve pulmonary function in severe COVID-19 respiratory failure, and is it safe?<h4>Study design and methods</h4>Adults with COVID-19-induced respiratory failure were randomized from May14, 2 ...[more]

PMID: 34592318

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Dataset Information

Study of Alteplase for Respiratory Failure in SARS-CoV-2 COVID-19: A Vanguard Multicenter, Rapidly Adaptive, Pragmatic, Randomized Controlled Trial.

Background

Research question

Study design and methods

Results

Interpretation

Trial registry

Clinicaltrials

Publications

Study of Alteplase for Respiratory Failure in SARS-CoV-2 COVID-19: A Vanguard Multicenter, Rapidly Adaptive, Pragmatic, Randomized Controlled Trial.

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