Catheter-Related Early Thromboprophylaxis with Enoxaparin Studies
- Registration Number
- NCT04924322
- Lead Sponsor
- Yale University
- Brief Summary
The goal of the CRETE Studies is to investigate the newly identified age-dependent heterogeneity in the efficacy of enoxaparin in reducing the risk of central venous catheter-associated deep venous thrombosis in critically ill children.
- Detailed Description
Pediatric venous thromboembolism (VTE), which is predominantly deep venous thrombosis (DVT), is a top contributor to harm in hospitalized children. Its incidence increased by \>300% in the past 2 decades. Critical illness and central venous catheter (CVC) are the most important risk factors for VTE in children. Among critically ill children, the risk of CVC-associated DVT (CADVT) is as high as 54% with 72% of cases in infants \<1-year old. Pharmacologic prophylaxis is the most effective strategy against VTE in adults. However, due to paucity of age-appropriate evidence on its efficacy against CADVT, pharmacologic prophylaxis is uncommon in children. Extrapolation of evidence from adults is not appropriate because the hemostatic system changes significantly with age. The investigators recently completed a Bayesian phase 2b randomized clinical trial. In this trial, the investigators randomized critically ill children to early administration of prophylactic dose of enoxaparin, the most commonly used anticoagulant for prophylaxis, or usual care. Prophylaxis with enoxaparin appeared to reduce the risk of CADVT by half. In post hoc analyses, reduction was limited to older children 1-17 years old. The goal of the CRETE Studies is to investigate this newly identified age-dependent heterogeneity in the efficacy of enoxaparin in reducing the risk of CADVT in critically ill children. To achieve this goal, the investigators aim (1) to confirm the efficacy and safety of early administration of prophylactic dose of enoxaparin in reducing the risk of CADVT in critically ill older children; (2) to determine the efficacy and safety of early administration of therapeutic dose of enoxaparin in reducing the risk of CADVT in critically ill infants; and, (3) to probe the mechanisms that underly the age-dependent heterogeneity in the efficacy of enoxaparin in reducing the risk of CADVT in critically ill children. The investigators will conduct 2 multicenter Bayesian explanatory randomized clinical trials in parallel to address Specific Aims 1 and 2. Depending on age, subjects will be randomized to different doses of enoxaparin vs usual care. Subjects will be systematically assessed for the development of CADVT using ultrasonography and clinically for bleeding. Using plasma obtained from subjects in the 2 trials, the investigators will conduct an exploratory mechanistic nested case-control study to address Specific Aim 3. Biomarkers of selected mechanisms underlying CVC-associated thrombus formation, particularly thrombin generation, will be compared between subjects with and without CADVT. The investigators will use Bayesian methods to improve the efficiency in the conduct and analyses of these studies. The CRETE Studies will provide high-quality age-appropriate evidence that will inform preventive strategies against CADVT and decrease harm in hospitalized children.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 258
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Enoxaparin (Older Children Prophylactic) Enoxaparin Prophylactic dose of enoxaparin for older children 1-17 years old. Enoxaparin (Infants Therapeutic High Anti-Xa Target) Enoxaparin Therapeutic dose of enoxaparin for infants \<1 year old with anti-Xa target of \>0.5-1 IU/mL. Enoxaparin (Infants Therapeutic Low Anti-Xa Target) Enoxaparin Therapeutic dose of enoxaparin for infants \<1 year old with anti-Xa target of 0.2-0.5 IU/mL.
- Primary Outcome Measures
Name Time Method Number of children with CADVT Up to removal of CVC (maximum of 28 days) Thrombus in the central vein where the CVC was inserted that is diagnosed with systematic ultrasonographic surveillance.
- Secondary Outcome Measures
Name Time Method Number of children with clinically apparent CADVT Up to removal of CVC (maximum of 28 days) Any CADVT, except one that is only diagnosed with the systematic ultrasonographic surveillance.
Number of children with any bleeding Maximum of 36 hours after the last dose of enoxaparin Any overt or macroscopic evidence of bleeding.
Number of children with any VTE Up to removal of CVC (maximum of 28 days) Thrombus in the deep vein of any extremity or PE that is confirmed radiologically
Number of children with clinically apparent VTE Up to removal of CVC (maximum of 28 days) Any VTE, except one that is only diagnosed with the systematic ultrasonographic surveillance.
Number of children with heparin-induced thrombocytopenia Maximum of 36 hours after the last dose of enoxaparin Unexplained drop in platelet count to \<50 x 10\^3/mcL or by 50 percent of baseline platelet count in the ICU within 21 days following exposure to heparin, and with a positive anti-platelet factor 4 antibody.
Number of children with clinically relevant bleeding Maximum of 36 hours after the last dose of enoxaparin Bleeding that is fatal, with drop in hemoglobin by ≥2 g/dl in 24 hours, requires medical or surgical intervention to restore hemostasis, or in the retroperitoneum, pulmonary or central nervous system.
Trial Locations
- Locations (21)
Children's of Alabama
🇺🇸Birmingham, Alabama, United States
Arkansas Children's Hospital
🇺🇸Little Rock, Arkansas, United States
Children's Hospital Colorado
🇺🇸Aurora, Colorado, United States
Yale-New Haven Children's Hospital
🇺🇸New Haven, Connecticut, United States
University of Florida -UF Health
🇺🇸Gainesville, Florida, United States
Johns Hopkins All Children's
🇺🇸Saint Petersburg, Florida, United States
Children's Hospital of Illinois at OSF Saint Francis Medical Center
🇺🇸Peoria, Illinois, United States
Stead Family Children's Hospital
🇺🇸Iowa City, Iowa, United States
Children's Hospital St. Louis
🇺🇸Saint Louis, Missouri, United States
Hassenfeld Children's Hospital
🇺🇸New York, New York, United States
New York Presbyterian Hospital
🇺🇸New York, New York, United States
Golisano Children's Hospital
🇺🇸Rochester, New York, United States
Maria Fareri Children's Hospital
🇺🇸Valhalla, New York, United States
UH Rainbow Babies & Children's Hospital
🇺🇸Cleveland, Ohio, United States
Nationwide Children's Hospital
🇺🇸Columbus, Ohio, United States
University of Oklahoma
🇺🇸Oklahoma City, Oklahoma, United States
Penn State Hershey Children's Hospital
🇺🇸Hershey, Pennsylvania, United States
Children's Hospital of Philadelphia
🇺🇸Philadelphia, Pennsylvania, United States
Dell Children's Medical Canter
🇺🇸Austin, Texas, United States
Children's Hospital of Richmond
🇺🇸Richmond, Virginia, United States
Children's Hospital Wisconsin
🇺🇸Milwaukee, Wisconsin, United States