Catheter-Related Early Thromboprophylaxis With Enoxaparin (CRETE) Trial
- Registration Number
- NCT03003390
- Lead Sponsor
- Yale University
- Brief Summary
The purpose of this phase 2a, multi-center, randomized controlled study, is to explore the efficacy of early prophylaxis against catheter-associated deep venous thrombosis (CADVT) in critically ill children.
- Detailed Description
Critical illness and the presence of a central venous catheter (CVC) are the most important risk factors for deep venous thrombosis (DVT) in children. Catheter-associated thrombosis (CADVT) is highly prevalent and associated with poor outcomes in critically ill children. Yet, based on underpowered pediatric trials, prophylaxis against CADVT is not recommended in children. The recommendation to provide prophylaxis against thrombosis in critically ill adults should not be applied to children because the hemostatic system and co-morbidities vastly differ between age groups. Pivotal trials are urgently needed to determine whether prophylaxis can prevent CADVT and its complications in critically ill children. However, the timing and extent of reduction in thrombin generation, the biochemical goal of prophylaxis, needed to prevent CADVT in children are unclear. The goal of this application is to explore the efficacy of early prophylaxis against CADVT in critically ill children. Aim 1 is to obtain preliminary evidence on the effect of early prophylaxis on the incidence of CADVT in critically ill children. Based on the natural history of CADVT, we hypothesize that among critically ill children, prophylaxis administered \<24 hours after catheter insertion decreases the incidence of ultrasound-diagnosed CADVT compared with no prophylaxis. In this phase 2a trial, children admitted to the intensive care unit with a newly inserted central venous catheter will receive enoxaparin adjusted according to anti-Xa activity, a control group will not receive enoxaparin adjusted according to anti-Xa activity. Enoxaparin has become the "standard" pediatric anticoagulant for prophylaxis despite the absence of conclusive data. We will use Bayesian approach to determine whether further trials are warranted. Aim 2 is to evaluate the effect of an anti-Xa activity-directed prophylactic strategy on thrombin generation in critically ill children. We hypothesize that among critically ill children, standard prophylactic dose of enoxaparin adjusted by anti-Xa activity reduces thrombin generation to \<700 nanomolar-minute (nM.min), as measured by endogenous thrombin potential (ETP). In non-critically ill adults, prophylactic dose of enoxaparin proven to prevent DVT reduces ETP to \<700 nM.min. Endogenous thrombin potential is the best available measure of thrombin generation. We will measure endogenous thrombin potential and anti-Xa activity at multiple time points then examine their relationship in all children enrolled in the phase 2a trial. The proposed research challenges the current paradigm on prophylaxis against CADVT in children. High quality evidence is needed to prevent CADVT and its complications in this vulnerable population.
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 51
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Prophylaxis with enoxaparin Enoxaparin A clinical nurse will administer enoxaparin subcutaneously \<24 hours after insertion of the central venous catheter and then give enoxaparin subcutaneously every 12 hours until the removal of the catheter.
- Primary Outcome Measures
Name Time Method Number of Participants With Central Venous Catheter (CVC)- Associated Deep Vein Thrombosis (DVT) Up to removal of CVC, an average of 6 days Thrombus in the central vein where the CVC was inserted that is clinically suspected then confirmed radiologically, an incidental radiologic finding, or diagnosed with the study-related active surveillance ultrasound
Endogenous Thrombin Potential Day of, day after and day 4 after insertion of the CVC An established measure of coagulation status and is the best method to measure thrombin generation. It directly measures the amount of thrombin generation over time capturing the effects of natural (i.e., subject's coagulation status) and pharmacological (e.g., enoxaparin) pro- and anticoagulants. Endogenous thrombin potential is measured using thrombin generation assay.
- Secondary Outcome Measures
Name Time Method Number With Other Thromboembolic Events Up to removal of CVC, an average of 6 days Thrombus in the deep vein of any extremity or PE that is clinically suspected then confirmed radiologically, an incidental radiologic finding, excluding DVT diagnosed with the study-related active surveillance ultrasound
Length of Stay in the Pediatric Intensive Care Unit in Days Up to day of discharge from the pediatric intensive care unit, an average of 10 days Duration of stay in the pediatric intensive care unit from the day of enrollment
Number With Clinically Relevant Bleeding Up to 30 hours after the last enoxaparin dose Bleeding that is fatal, associated with a decrease in hemoglobin by ≥2 g/dl in 24 hours, requires medical or surgical intervention to restore hemostasis, or is in the retroperitoneum, pulmonary, intracranial or central nervous system as defined by International Society of Thrombosis and Haemostasis
Number With Laboratory Confirmed Heparin-induced Thrombocytopenia Up to removal of CVC, an average of 6 days Heparin-induced thrombocytopenia that is diagnosed with a positive serotonin release assay
Number of Mortality Up to day of discharge from the hospital, average of 18 days In-hospital mortality during the subject's admission
Number of Enrolled Eligible Children Up to 24 hours after insertion of CVC Number of eligible children enrolled in the study.
Time to Target Anti-Xa Activity Up to removal of CVC, an average of 6 days Time from insertion of the CVC to time that anti-Xa activity was within 0.2-0.5 IU/mL.
Number of Missed Doses of Enoxaparin Up to removal of CVC, an average of 6 days Number of doses of enoxaparin that were not administered. This outcome measure was only applicable to the enoxaparin arm.
Number of Children With Ultrasound Up to 24 hours after removal of CVC Number of children in whom ultrasound was not performed.
Length of Stay in the Hospital Up to day of discharge from the hospital, an average of 18 days Duration of stay in the hospital from the day of enrollment
Time to 1st Dose of Enoxaparin Up to 48 hours after insertion of CVC Time to first dose of enoxaparin
Trial Locations
- Locations (6)
Saint Louis Children's Hospital-Washington University School of Medicine-
🇺🇸Saint Louis, Missouri, United States
Maria Fareri Children's Hospital
🇺🇸Valhalla, New York, United States
Yale University Yale New Haven Health
🇺🇸New Haven, Connecticut, United States
University of Rochester Medical Center-Golisano Children's Hospital-
🇺🇸Rochester, New York, United States
Weill Cornell Medicine
🇺🇸New York, New York, United States
Children's Hospital of Wisconsin/Medical College of Wisconsin
🇺🇸Milwaukee, Wisconsin, United States