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Anticoagulation and Antiplatelet Therapy for Prevention of Venous and Arterial Thrombotic Events in Critically Ill Patients With COVID-19: COVID-PACT

2022· article· en· W4293463343 on OpenAlexaff
Erin A. Bohula, David D. Berg, Mathew S. Lopes, Jean M. Connors, Ijlal Babar, Christopher F. Barnett, Sunit‐Preet Chaudhry, Amit Chopra, Wilson Ginete, Michael H. Ieong, Jason N. Katz, Edy Y. Kim, Julia Kuder, Emílio Mazza, Dalton McLean, Jarrod Mosier, Ari Moskowitz, Sabina A. Murphy, Michelle L. O’Donoghue, Jeong‐Gun Park, Rajnish Prasad, Christian T. Ruff, Mohamad N. Shahrour, Shashank S. Sinha, Stephen D. Wiviott, Sean van Diepen, Mark Zainea, Vivian M. Baird-Zars, Marc S. Sabatine, David A. Morrow, Kyung Ah Im, Retu Saxena, Brandon M. Wiley, Carina Benson, Roman Delamed, Nedaa Skeik, Ami Chopra, Marc A. Judson, Scott Beegle, Boris Shkolnik, Anupama Tiwari, Gregory F. Wu, Abhijit Raval, E. Branch, Franz Rischard, Cameron Hypes, Billie Bixby, Christian Bime, Madhan Sundaram, Nancy K. Sweitzer, Alfredo Vazquez Sandoval, Heath D. White, Katherine M. Berg, Shahzad Shaefi, Michael W. Donnino, Brett Carroll, Kimberly Ackerbauer, Jaime Murphy, Ankeet S. Bhatt, Alexander Blood, Siddharth Patel, Victor Luu, Shraddha Narechania, Austin Lorganger, Robert Plambeck, Ali Nayfeh, Michael Sanley, Michel Del Cor, A. J. Hegg, Winston Nara, M Snyder, Faisal Khan, Imad Shawa, Joshua Larned, Elias Collado, Mohammed Al Faiyumi, Rajeev Mehta, Sudarshan Komanapalli, Vijayadershan Muppidi, Mehul J. Desai, Casey M. Flanagan, Leonard Genovese, Tariq Haddad, Christopher R. King, Amber Peterson, Thane Htun, Elizabeth Pionk, Nicolas J. Mouawad, C. V. Nithish Kumar, Kevin Nguyen, Majid Mughal, Ryan Malek, Akarsh Parekh, Christopher Provenzano, Melissa Marie Ianitelli, Nicole Prentice-Gaytan, Adam Bykowski, Don Tait, Shelley Schendel, Varun Yalamanchili, Vasim Lala, Victor Hunyadi, Alexander Papolos, Benjamin B. Kenigsberg, Aarthi Shenoy, Thomas Stuckey, Douglas McQuaid, Praveen Mannam, Jeffrey McClung, Kent W. Nilsson, Andrew C. McKown, Jason B. Wells, David Hotchkin, Marc Jacobs, Wayne Strauss, Rick Balestra, V. Anik Sahni, R. Jeffrey Snell, Hussam Suradi, Sarah Sungurlu, J. Kuppy, Eileen Gajo, F. D. ADAMS, Abbas Shehadeh, Addi Suleiman, Harish Nandigam, Jihad Slim, Sardar Ijlal Babar, Dipti Baral, Talha Nawaz, Syed Abdullah Waheed, Randy Roth, Subhas Sitaula, S A Hayat, Jooby Babu, Jason Caberto, Victor W. Hsu, Robert W. Chang, Markian R. Bochan, Rafael Garcia‐Cortes, Hal A. Skopicki, On Chen, Lauren Pilato, Paul Richman, A. Adler, Praveen Sudhindra, Jamie Beversdorf, Ravindra Kashyap, Parth Mehta, Borna Mehrad, Ali Ataya, Jorge Lascano, Mark Brantly, Adam Austin, Eduard Koman, Thomas Galski, V Vineeth Kumar, Ayman O. Soubani, N. Harrison, Vineet Reddy, Audrey Fonkam

Bibliographic record

VenueCirculation · 2022
Typearticle
Languageen
FieldMedicine
TopicCOVID-19 Clinical Research Studies
Canadian institutionsUniversity of Alberta HospitalUniversity of Alberta
FundersEisaiARCA BiopharmaDaiichi-SankyoZora BiosciencesAmerican Heart AssociationAmerican Thoracic SocietyIntarcia TherapeuticsIonis PharmaceuticalsNational Institutes of HealthRegeneron PharmaceuticalsHarvard CatalystAlnylam PharmaceuticalsNovo NordiskVertex PharmaceuticalsAlexion PharmaceuticalsServierBayerCSL BehringAstraZenecaBristol-Myers SquibbPfizerAmgenBayer HealthCareKowa CompanySanofiBrigham and Women's HospitalJanssen Research and DevelopmentUnited States Agency for International Development
KeywordsMedicineIntensive care unitVenous thrombosisStroke (engine)Mechanical ventilationClinical endpointThrombosisPulmonary embolismRandomized controlled trialInternal medicine

Abstract

fetched live from OpenAlex

Background: The efficacy and safety of prophylactic full-dose anticoagulation and antiplatelet therapy in critically ill COVID-19 patients remain uncertain. Methods: COVID-PACT (Prevention of Arteriovenous Thrombotic Events in Critically-ill COVID-19 Patients Trial) was a multicenter, 2×2 factorial, open-label, randomized-controlled trial with blinded end point adjudication in intensive care unit–level patients with COVID-19. Patients were randomly assigned to a strategy of full-dose anticoagulation or standard-dose prophylactic anticoagulation. Absent an indication for antiplatelet therapy, patients were additionally randomly assigned to either clopidogrel or no antiplatelet therapy. The primary efficacy outcome was the hierarchical composite of death attributable to venous or arterial thrombosis, pulmonary embolism, clinically evident deep venous thrombosis, type 1 myocardial infarction, ischemic stroke, systemic embolic event or acute limb ischemia, or clinically silent deep venous thrombosis, through hospital discharge or 28 days. The primary efficacy analyses included an unmatched win ratio and time-to-first event analysis while patients were on treatment. The primary safety outcome was fatal or life-threatening bleeding. The secondary safety outcome was moderate to severe bleeding. Recruitment was stopped early in March 2022 (≈50% planned recruitment) because of waning intensive care unit–level COVID-19 rates. Results: At 34 centers in the United States, 390 patients were randomly assigned between anticoagulation strategies and 292 between antiplatelet strategies (382 and 290 in the on-treatment analyses). At randomization, 99% of patients required advanced respiratory therapy, including 15% requiring invasive mechanical ventilation; 40% required invasive ventilation during hospitalization. Comparing anticoagulation strategies, a greater proportion of wins occurred with full-dose anticoagulation (12.3%) versus standard-dose prophylactic anticoagulation (6.4%; win ratio, 1.95 [95% CI, 1.08–3.55]; P =0.028). Results were consistent in time-to-event analysis for the primary efficacy end point (full-dose versus standard-dose incidence 19/191 [9.9%] versus 29/191 [15.2%]; hazard ratio, 0.56 [95% CI, 0.32–0.99]; P =0.046). The primary safety end point occurred in 4 (2.1%) on full dose and in 1 (0.5%) on standard dose ( P =0.19); the secondary safety end point occurred in 15 (7.9%) versus 1 (0.5%; P =0.002). There was no difference in all-cause mortality (hazard ratio, 0.91 [95% CI, 0.56–1.48]; P =0.70). There were no differences in the primary efficacy or safety end points with clopidogrel versus no antiplatelet therapy. Conclusions: In critically ill patients with COVID-19, full-dose anticoagulation, but not clopidogrel, reduced thrombotic complications with an increase in bleeding, driven primarily by transfusions in hemodynamically stable patients, and no apparent excess in mortality. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT04409834.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.001
metaresearch head score (Gemma)0.008
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: Observational
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.010
Threshold uncertainty score0.964

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0010.008
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0000.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.055
GPT teacher head0.404
Teacher spread0.350 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one teacher head, not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designObservational
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

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Citations82
Published2022
Admission routes1
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