Evidence map›Paper›PMID 34592318›Full record

Trial reportChest2022

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

Christopher D Barrett, Hunter B Moore, Ernest E Moore, Janice Wang, Negin Hajizadeh, Walter L Biffl, Lawrence Lottenberg, Purvesh R Patel, Michael S Truitt, Robert C McIntyre and 29 more

Registry-linked trialOpen access · bronzeAbstract readClinical Trial, Phase IClinical Trial, Phase IIMulticenter Study
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Chest, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04357730 (Fibrinolytic Therapy to Treat ARDS in the Setting of COVID-19 Infection), which is not on this map. Cited by 43 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
43citing papers in PubMed, 2 pooled it
2.9field-weighted citation impact, top 7% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT04357730 phase2completednot on this map

Fibrinolytic Therapy to Treat ARDS in the Setting of COVID-19 Infection: A Phase 2a Clinical Trial

TypeinterventionalSponsorDenver Health and Hospital AuthorityRan2020 to 2021Enrolled50ConditionsSevere Acute Respiratory Syndrome, Respiratory Failure, Acute Respiratory Distress SyndromeArmsAlteplase 50 MG [Activase]
3 · Its place in the literature

Who cites it

43 citing papers in PubMed, 2 syntheses or guidelines pooled it, 53 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Trial
  4. [Sepsis-induced coagulopathy].Die Anaesthesiologie · 2026
    Review
  5. A grading system of dynamic fibrinolysis resistance in sepsis associates with ICU outcomes.American journal of respiratory and critical care medicine · 2026
    Article
  6. Review
  7. Article
  8. Article
  9. Review
  10. A comparison of anti-coagulation monitoring tests in ICU patients receiving a continuous infusion of unfractionated heparin.Critical care and resuscitation : journal of the Australasian Academy of Critical Care Medicine · 2024
    Article
  11. Article
  12. Article
  13. Article
  14. Article
  15. Review
  16. Article
  17. Article
  18. Fibrinolytic system and COVID-19: From an innovative view of epithelial ion transport.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2023
    Review
  19. Article
  20. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

39 authors at 12 institutions in 1 country.

Christopher D BarrettDepartment of Surgery, Boston University School of Medicine, Boston, MA; Department of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA; Koch Institute for Integrative Cancer Research, Center for Precision Cancer Medicine, Departments of Biological Engineering and Biology, Massachusetts Institute of Technology, Cambridge, MA.
Hunter B MooreDepartment of Surgery, University of Colorado Denver, Aurora, CO.
Ernest E MooreDepartment of Surgery, University of Colorado Denver, Aurora, CO; Ernest E. Moore Shock Trauma Center at Denver Health, Department of Surgery, Denver, CO. Electronic address: ernest.moore@dhha.org.
Janice WangFeinstein Institutes for Medical Research, Northwell Health, Manhasset, NY.
Negin HajizadehFeinstein Institutes for Medical Research, Northwell Health, Manhasset, NY.
Walter L BifflDivision of Trauma/Acute Care Surgery, Department of Surgery, Scripps Memorial Hospital La Jolla, La Jolla, CA.
Lawrence LottenbergDepartment of Surgery, St. Mary's Medical Center, Florida Atlantic University, West Palm Beach, FL.
Purvesh R PatelDepartment of Medicine, Baylor College of Medicine, Houston, Dallas, TX.
Michael S TruittDepartment of Surgery, Methodist Dallas Medical Center, Dallas, TX.
Robert C McIntyreDepartment of Surgery, University of Colorado Denver, Aurora, CO.
Todd M BullDivision of Pulmonary Sciences and Critical Care Medicine, Department of Medicine, University of Colorado Denver, Aurora, CO.
Lee Anne AmmonsErnest E. Moore Shock Trauma Center at Denver Health, Department of Surgery, Denver, CO.
Arsen GhasabyanErnest E. Moore Shock Trauma Center at Denver Health, Department of Surgery, Denver, CO.
James ChandlerErnest E. Moore Shock Trauma Center at Denver Health, Department of Surgery, Denver, CO.
Ivor S DouglasDivision of Pulmonary, Critical Care, and Sleep Medicine, Department of Medicine, Denver Health Medical Center, Denver, CO.
Eric P SchmidtDivision of Pulmonary, Critical Care, and Sleep Medicine, Department of Medicine, Denver Health Medical Center, Denver, CO.
Peter K MooreDivision of Pulmonary Sciences and Critical Care Medicine, Department of Medicine, University of Colorado Denver, Aurora, CO.
Franklin L WrightDepartment of Surgery, University of Colorado Denver, Aurora, CO.
Ramona RamdeoFeinstein Institutes for Medical Research, Northwell Health, Manhasset, NY.
Robert BorregoDivision of Pulmonary/Critical Care Medicine, Department of Medicine, Scripps Memorial Hospital La Jolla, La Jolla, CA.
Mario RuedaDivision of Pulmonary/Critical Care Medicine, Department of Medicine, Scripps Memorial Hospital La Jolla, La Jolla, CA.
Achal DhupaDivision of Trauma/Acute Care Surgery, Department of Surgery, Scripps Memorial Hospital La Jolla, La Jolla, CA.
D Scott McCaulDivision of Trauma/Acute Care Surgery, Department of Surgery, Scripps Memorial Hospital La Jolla, La Jolla, CA.
Tala DandanDivision of Trauma/Acute Care Surgery, Department of Surgery, Scripps Memorial Hospital La Jolla, La Jolla, CA.
Pralay K SarkarDepartment of Medicine, Baylor College of Medicine, Houston, Dallas, TX.
Benazir KhanDepartment of Medicine, Baylor College of Medicine, Houston, Dallas, TX.
Coimbatore SreevidyaDepartment of Medicine, Baylor College of Medicine, Houston, Dallas, TX.
Conner McDanielDepartment of Surgery, Methodist Dallas Medical Center, Dallas, TX.
Heather M Grossman VernerClinical Research Institute, Methodist Dallas Medical Center, Dallas, TX.
Christopher PearcyDepartment of Surgery, Methodist Dallas Medical Center, Dallas, TX.
Lorenzo Anez-BustillosDepartment of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA.
Elias N Baedorf-KassisDivision of Pulmonary and Critical Care Medicine, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA.
Rashi JhunjhunwalaDepartment of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA.
Shahzad ShaefiDepartment of Anesthesia, Critical Care and Pain Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston.
Krystal CapersDepartment of Anesthesia, Critical Care and Pain Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston.
Valerie Banner-GoodspeedDepartment of Anesthesia, Critical Care and Pain Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston.
Daniel S TalmorDepartment of Anesthesia, Critical Care and Pain Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston.
Angela SauaiaErnest E. Moore Shock Trauma Center at Denver Health, Department of Surgery, Denver, CO; Colorado School of Public Health and Department of Surgery, University of Colorado Denver, Denver, CO.
Michael B YaffeDepartment of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA; Koch Institute for Integrative Cancer Research, Center for Precision Cancer Medicine, Departments of Biological Engineering and Biology, Massachusetts Institute of Technology, Cambridge, MA.
University of Colorado Denver · USScripps Memorial Hospital · USBeth Israel Deaconess Medical Center · USDenver Health Medical Center · USBaylor College of Medicine · USHarvard University · USMethodist Dallas Medical Center · USFeinstein Institute for Medical Research · USClinical Research Institute · USFlorida Atlantic University · USMassachusetts Institute of Technology · USNorthwell Health · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundPulmonary 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

methodsAdults 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 Pao

resultsFifty 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 Pao

interpretationThe 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.

Indexed as

PandemicsSARS-CoV-2AdolescentAdultAgedCOVID-19Cross-Sectional StudiesFemaleFibrinolytic AgentsFollow-Up StudiesHumansMaleMiddle AgedPartial Thromboplastin TimeRespiratory InsufficiencyRetrospective StudiesFibrinolytic AgentsTissue Plasminogen ActivatorARDSCOVID-19fibrinolysispulmonary failuretissue plasminogen activator (tPA)

Identifiers

PMID34592318
PMCPMC8474873
OpenAlexW3203445105

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.