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Rapid Point-of-Care Assay of Enoxaparin Anticoagulant Efficacy in Whole Blood
Published on: October 12, 2012
Protocol for the Catheter-Related Early Thromboprophylaxis With Enoxaparin (CRETE) Studies
E Vincent S Faustino1, Sarah B Kandil1, Matthew K Leroue2
1Department of Pediatrics, Yale School of Medicine, New Haven, CT.
Insights
Enoxaparin prophylaxis effectively reduced central venous catheter-associated deep venous thrombosis in critically ill older children, but not infants. The CRETE studies investigate this age-dependent difference in enoxaparin efficacy for preventing CADVT.
Area of Science:
- Pediatric Critical Care Medicine
- Pharmacology and Therapeutics
- Thrombosis and Hemostasis
Background:
- Previous research indicated enoxaparin prophylaxis reduced central venous catheter (CVC)-associated deep venous thrombosis (CADVT) in critically ill older children.
- However, this benefit was not observed in infants, suggesting age-dependent heterogeneity in enoxaparin efficacy.
Purpose of the Study:
- To investigate the age-dependent heterogeneity in the efficacy of enoxaparin prophylaxis for preventing CADVT in critically ill children.
- To further elucidate the mechanisms underlying these age-specific responses.
Main Methods:
- Two parallel, multicenter Bayesian superiority explanatory randomized clinical trials (RCTs) for older children (phase 3) and infants (phase 2b).
- An exploratory mechanistic nested case-control study.
- Participants: Critically ill children (older children 1-17 years; infants <1 year corrected age) with a new CVC, excluding those with bleeding risk.
Main Results:
- Older children randomized 2:1 to enoxaparin or usual care; infants randomized 1:1:1 to two enoxaparin anti-Xa ranges or usual care.
- Primary outcome assessed by ultrasonography after CVC removal for CADVT.
- Secondary outcomes include bleeding events and markers of thrombin generation.
Conclusions:
- The CRETE studies aim to clarify the role of enoxaparin in preventing CADVT across different pediatric age groups.
- Findings will inform optimal thromboprophylaxis strategies for critically ill children with CVCs.
Objectives:
In post hoc analyses of our previous phase 2b Bayesian randomized clinical trial (RCT), prophylaxis with enoxaparin reduced central venous catheter (CVC)-associated deep venous thrombosis (CADVT) in critically ill older children but not in infants. The goal of the Catheter-Related Early Thromboprophylaxis with Enoxaparin (CRETE) Studies is to investigate this newly identified age-dependent heterogeneity in the efficacy of prophylaxis with enoxaparin against CADVT in critically ill children.
Design:
Two parallel, multicenter Bayesian superiority explanatory RCTs, that is, phase 3 for older children and phase 2b for infants, and an exploratory mechanistic nested case-control study (Trial Registration ClinicalTrials.gov NCT04924322, June 7, 2021).
Setting:
At least 15 PICUs across the United States.
Patients:
Older children 1-17 years old ( n = 90) and infants older than 36 weeks corrected gestational age younger than 1 year old ( n = 168) admitted to the PICU with an untunneled CVC inserted in the prior 24 hours. Subjects with or at high risk of clinically relevant bleeding will be excluded.
Interventions:
Prophylactic dose of enoxaparin starting at 0.5 mg/kg then adjusted to anti-Xa range of 0.2-0.5 international units (IU)/mL for older children and therapeutic dose of enoxaparin starting at 1.5 mg/kg then adjusted to anti-Xa range of greater than 0.5-1.0 IU/mL or 0.2-0.5 IU/mL for infants while CVC is in situ.
Measurements And Main Results:
Randomization is 2:1 to enoxaparin or usual care (no enoxaparin) for older children and 1:1:1 to either of 2 anti-Xa ranges of enoxaparin or usual care for infants. Ultrasonography will be performed after removal of CVC to assess for CADVT. Subjects will be monitored for bleeding. Platelet poor plasma will be analyzed for markers of thrombin generation. Samples from subjects with CADVT will be counter-matched 1:1 to subjects without CADVT from the opposite trial arm. Institutional Review Board approved the "CRETE Studies" on July 1, 2021. Enrollment is ongoing with planned completion in July 2025 for older children and July 2026 for infants.
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