LB 01.5 - Effect of the P-selectin Inhibitor Crizanlizumab on Survival Free of Organ Support in Patients Hospitalized for COVID-19: A Randomized Controlled Trial

Sunday, June 25, 2023

11:45 – 12:00 ET

Room: 517

Session Available As: Live-Streamed and On-Demand

Presenting Author(s)

Charles Lowenstein, MD

Chief of Cardiology
The Johns Hopkins University School of Medicine
Baltimore, Maryland, United States

Co-Author(s)

SS

Scott Solomon

Professor
Brigham and Women's Hospital
Boston, Massachusetts, United States
AB

Ankeet Bhatt

Professor
Brigham and Women's Hospital
Boston, Massachusetts, United States
AP

Alexander Peikert

Professor
Brigham and Women’s Hospital,
Boston, Massachusetts, United States
OV

Orly Vardeny

Professor
University of Minnesota
Minneapolis, Minnesota, United States
MK

Mikhail Kosiborod

Vice-President for Research
Saint Luke's Mid America Heart Institute
Kansas City, Kansas, United States
JB

Jeffrey S. Berger

Associate Professor of Medicine and Surgery
New York University Grossman School of Medicine
New York, New York, United States
HR

Harmony Reynolds

Professor
Cardiovascular Clinical Research Center, NYU Grossman School of Medicine
New York, New York, United States
AA

Andrew Althouse

Professor
University of Pittsburgh
Pittsburgh, Pennsylvania, United States
EL

Eric Leifer

Mathematical Statistician
National Heart, Lung, and Blood Institute, NIH
Bethesda, Maryland, United States
AK

Andrei Kindzelski

Program Director
National Institutes of Health
Bethesda, Maryland, United States
Mary Cushman, MD, MSc (she/her/hers)

Professor
Department of Medicine, Larner College of Medicine at the University of Vermont, USA
Colchester, Vermont, United States
MG

Michelle Gong

Professor
Montefiore Medical Center
New York, New York, United States
LK

Lucy Kornblith

Professor
University of California, San Francisco,
San Francisco, California, United States
KK

Keri Kim

Professor
University of Illinois, Chicago
Chicago, Illinois, United States
Lisa Baumann Kreuziger, MD, MS (she/her/hers)

Investigator
Versiti Blood Research Institute, Versiti, Milwaukee, WI, USA
Milwaukee, Wisconsin, United States
BK

Bridget-Anne Kirwan

Chief Scientific Officer and Chief Executive Officer
SOCAR Research SA
Nyon, Vaud, Switzerland
MG

Mark Geraci

Associate Vice Chancellor for Interdisciplinary Research
University of Pittsburgh
Pittsburgh, Pennsylvania, United States
Matthew D. Neal, MD FACS (he/him/his)

Associate Professor
University of Pittsburgh
Pittsburgh, Pennsylvania, United States
JH

Judith Hochman

Professor & Senior Associate Dean for Clinical Sciences
NYU Langone Health
New York, New York, United States

Background: COVID-19 is associated with endothelial injury, microvascular inflammation, and thrombosis. Activated endothelial cells release and express P-selectin and von Willebrand Factor, both of which are elevated in severe COVID-19 and may be implicated in the disease pathophysiology. We hypothesized that crizanlizumab, a humanized monoclonal antibody to P-selectin, would reduce morbidity and mortality in patients hospitalized for COVID-19.

Aims: To test the effect of crizanlizumab on morbidity and mortality of inpatients with COVID-19.

Methods:

Methods: An international, adaptive randomized-controlled platform trial, funded by NHLBI, randomly assigned 422 patients hospitalized with moderate or severe COVID-19 to receive either a single infusion of the P-selectin inhibitor crizanlizumab (at a dose of 5 mg/kg) plus standard-of-care, or standard-of-care alone, in an open-label 1:1 ratio. The primary outcome was organ support-free days, evaluated on an ordinal scale consisting of the number of days alive free of organ support through the first 21 days after trial entry. Institutional review board approval was provided at each site. All patients or their representatives provided written informed consent.

Results: The study was stopped for futility by the data safety monitoring committee. Among 421 randomized patients with known 21-day outcome, 163 (77%) patients randomized to the crizanlizumab plus standard-of-care arm did not require any respiratory or cardiovascular organ support compared with 169 (80%) in the standard-of-care only arm. The adjusted OR for the effect of crizanlizumab on organ support–free days was 0.70 (95% CrI, 0.43 to 1.16), where OR>1 indicates treatment benefit, yielding a posterior probability of futility Pr(OR < 1.2) of 98% and a posterior probability of inferiority Pr(OR < 1.0) of 91% (Figure). Overall, there were 37 deaths (17.5%) in the crizanlizumab arm and 27 (12.8%) deaths in the standard-of-care arm (HR=1.42, 95% CrI 0.90-2.36, Pr(HR>1) = 0.934).

Conclusion(s): Crizanlizumab, a P-selectin inhibitor, did not improve organ support free days in patients hospitalized with COVID-19.