Dataset Information

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

ABSTRACT:

Background

COVID-19 has been associated with endothelial injury, resultant 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 death in patients hospitalized for COVID-19.

Methods

An international, adaptive, randomized controlled platform trial, funded by the National Heart, Lung, and Blood Institute, randomly assigned 422 patients hospitalized with COVID-19 with moderate or severe illness 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.

Results

The study was stopped for futility by the data safety monitoring committee. Among 421 randomized patients with known 21-day outcomes, 163 patients (77%) 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-alone arm. The adjusted odds ratio for the effect of crizanlizumab on organ support-free days was 0.70 (95% CI, 0.43-1.16), where an odds ratio >1 indicates treatment benefit, yielding a posterior probability of futility (odds ratio <1.2) of 98% and a posterior probability of inferiority (odds ratio <1.0) of 91%. Overall, there were 37 deaths (17.5%) in the crizanlizumab arm and 27 deaths (12.8%) in the standard-of-care arm (hazard ratio, 1.33 [95% CrI, 0.85-2.21]; [probability of hazard ratio>1] = 0.879).

Conclusions

Crizanlizumab, a P-selectin inhibitor, did not result in improvement in organ support-free days in patients hospitalized with COVID-19.

Registration

URL: https://www.

Clinicaltrials

gov; Unique identifier: NCT04505774.

SUBMITTER: Solomon SD

PROVIDER: S-EPMC10373640 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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

Solomon Scott D SD Lowenstein Charles J CJ Bhatt Ankeet S AS Peikert Alexander A Vardeny Orly O Kosiborod Mikhail N MN Berger Jeffrey S JS Reynolds Harmony R HR Mavromichalis Stephanie S Barytol Anya A Althouse Andrew D AD Luther James F JF Leifer Eric S ES Kindzelski Andrei L AL Cushman Mary M Gong Michelle N MN Kornblith Lucy Z LZ Khatri Pooja P Kim Keri S KS Baumann Kreuziger Lisa L Wahid Lana L Kirwan Bridget-Anne BA Geraci Mark W MW Neal Matthew D MD Hochman Judith S JS

Circulation 20230625 5

<h4>Background</h4>COVID-19 has been associated with endothelial injury, resultant 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 death in patients hospitalized for COVID-19.<h4>Methods</h4>An international, ...[more]

PMID: 37356038

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Project description:BackgroundRecipients of an organ transplantation face a number of challenges and often need to change their health behaviour. Good self-management skills are essential for optimal clinical outcomes. However, few interventions are available to support post-transplant self-management. To fill this gap, we developed a self-management support intervention offered by nurse practitioners. The primary aim of the study is to implement and test the effectiveness of the ZENN intervention in promoting self-management skills among heart, kidney liver and lung transplant recipients in comparison to standard care. The secondary aim is to assess the self-management support skills of nurse practitioners who will deliver the intervention.MethodsThis multi-centre stepped-wedge randomized controlled trial will take place from September 2020 until May 2023. All departments will commence with inclusion of patients in the control period. Each department will be randomly assigned to a start date (step in the wedge) to commence the experimental period. Patients in the control period will receive standard care and will be asked to complete questionnaires at baseline (T0), 6 months (T1) and 12 months (T2), to assess self-management, self-regulation, quality of life and adherence. During the experimental period, patients will receive standard care plus the ZENN intervention and receive the same set of questionnaires as participants in the control period. Nurse practitioners will complete a baseline and follow-up questionnaire to assess differences in self-management support skills. Video recordings of outpatient clinic consultations during the control and experimental periods will determine the differences in nurses' needs-thwarting and needs-supporting skills between the control and experimental period.DiscussionThe ZENN intervention could be a useful approach to support patients' self-management skills after organ transplantation and thus promote clinical outcomes as well as avoid adverse events.Trial registrationDutch Trial Register NL8469 . Registered on March 19, 2020.

Dataset Information

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

Background

Methods

Results

Conclusions

Registration

Clinicaltrials

Publications

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

Similar Datasets

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