Efficacy of Early Prophylaxis Against Catheter-Associated Thrombosis in Critically Ill Children: A Bayesian Phase 2b Randomized Clinical Trial

E Vincent S Faustino; Veronika Shabanova; Leslie J Raffini; Sarah B Kandil; Simon Li; Matthew G Pinto; Jill M Cholette; Sheila J Hanson; Marianne E Nellis; Cicero T Silva; Ranjit Chima; Anjali Sharathkumar; Kimberly A Thomas; Tara McPartland; Joana A Tala; Philip C Spinella; CRETE Trial Investigators and the Pediatric Critical Care Blood Research Network (BloodNet) of the Pediatric Acute Lung Injury and Sepsis Investigators Network (PALISI)

doi:10.1097/CCM.0000000000004784

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Efficacy of Early Prophylaxis Against Catheter-Associated Thrombosis in Critically Ill Children: A Bayesian Phase 2b Randomized Clinical Trial

Journal article

Peer reviewed

Efficacy of Early Prophylaxis Against Catheter-Associated Thrombosis in Critically Ill Children: A Bayesian Phase 2b Randomized Clinical Trial

E Vincent S Faustino, Veronika Shabanova, Leslie J Raffini, Sarah B Kandil, Simon Li, Matthew G Pinto, Jill M Cholette, Sheila J Hanson, Marianne E Nellis, Cicero T Silva, …

Critical care medicine, Vol.49(3), pp.e235-e246

03/01/2021

DOI: 10.1097/CCM.0000000000004784

PMCID: PMC7902342

PMID: 33372745

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https://www.ncbi.nlm.nih.gov/pmc/articles/7902342View

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Abstract

We obtained preliminary evidence on the efficacy of early prophylaxis on the risk of central venous catheter-associated deep venous thrombosis and its effect on thrombin generation in critically ill children. Bayesian phase 2b randomized clinical trial. Seven PICUs. Children less than 18 years old with a newly inserted central venous catheter and at low risk of bleeding. Enoxaparin adjusted to anti-Xa level of 0.2-0.5 international units/mL started at less than 24 hours after insertion of central venous catheter (enoxaparin arm) versus usual care without placebo (usual care arm). At the interim analysis, the proportion of central venous catheter-associated deep venous thrombosis on ultrasonography in the usual care arm, which was 54.2% of 24 children, was significantly higher than that previously reported. This resulted in misspecification of the preapproved Bayesian analysis, reversal of direction of treatment effect, and early termination of the randomized clinical trial. Nevertheless, with 30.4% of 23 children with central venous catheter-associated deep venous thrombosis on ultrasonography in the enoxaparin arm, risk ratio of central venous catheter-associated deep venous thrombosis was 0.55 (95% credible interval, 0.24-1.11). Including children without ultrasonography, clinically relevant central venous catheter-associated deep venous thrombosis developed in one of 27 children (3.7%) in the enoxaparin arm and seven of 24 (29.2%) in the usual care arm (p = 0.02). Clinically relevant bleeding developed in one child randomized to the enoxaparin arm. Response profile of endogenous thrombin potential, a measure of thrombin generation, was not statistically different between trial arms. These findings suggest the efficacy and safety of early prophylaxis that should be validated in a pivotal randomized clinical trial.

Adolescent

Anticoagulants - administration & dosage

Anticoagulants - adverse effects

Bayes Theorem

Catheterization, Central Venous - adverse effects

Central Venous Catheters - adverse effects

Child

Child, Preschool

Critical Illness

Double-Blind Method

Drug Administration Schedule

Enoxaparin - administration & dosage

Enoxaparin - adverse effects

Humans

Male

Pre-Exposure Prophylaxis

Venous Thrombosis - prevention & control

Details

Title: Subtitle: Efficacy of Early Prophylaxis Against Catheter-Associated Thrombosis in Critically Ill Children: A Bayesian Phase 2b Randomized Clinical Trial
Creators: E Vincent S Faustino - Yale School of Medicine
Veronika Shabanova - Yale School of Medicine
Leslie J Raffini - Children's Hospital of Philadelphia
Sarah B Kandil - Yale School of Medicine
Simon Li - Maria Fareri Children's Hospital
Matthew G Pinto - Maria Fareri Children's Hospital
Jill M Cholette - Golisano Children's Hospital
Sheila J Hanson - Medical College of Wisconsin
Marianne E Nellis - NewYork–Presbyterian Hospital
Cicero T Silva - Yale School of Medicine
Ranjit Chima - Cincinnati Children's Hospital Medical Center
Anjali Sharathkumar - University of Iowa
Kimberly A Thomas - Washington University in St. Louis
Tara McPartland - Yale School of Medicine
Joana A Tala - Pediatric Intensive Care Unit, Yale–New Haven Children's Hospital, New Haven, CT
Philip C Spinella - Washington University in St. Louis
CRETE Trial Investigators and the Pediatric Critical Care Blood Research Network (BloodNet) of the Pediatric Acute Lung Injury and Sepsis Investigators Network (PALISI)
Resource Type: Journal article
Publication Details: Critical care medicine, Vol.49(3), pp.e235-e246
DOI: 10.1097/CCM.0000000000004784
PMID: 33372745
PMCID: PMC7902342
NLM abbreviation: Crit Care Med
ISSN: 1530-0293
eISSN: 1530-0293
Grant note: R21 HD089131 / NICHD NIH HHS UL1 RR024139 / NCRR NIH HHS UL1 TR001863 / NCATS NIH HHS
Language: English
Date published: 03/01/2021
Academic Unit: Stead Family Department of Pediatrics; Hematology/Oncology
Record Identifier: 9984354038602771

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