Collaborative Risk-stratified Investigation in Teen Inpatients With Critical Illness: Anticoagulation With LMWH in Kids for ThromboProphylaxis (CRITICAL-Kids-TP) (CRITICALKidsTP)

Johns Hopkins Medicine

Status and phase

Begins enrollment in 8 months

Phase 3

Conditions

Venous Thromboembolism (VTE)

Treatments

Drug: Dalteparin

Study type

Interventional

Funder types

Other

Identifiers

NCT06628778

IRB00469377 - CRITICAL-Kids-TP

Details and patient eligibility

About

Critically ill adolescents are at greatest risk for developing hospital-acquired venous thromboembolism. To date, no phase 3 randomized controlled trials have been conducted for pharmacological thromboprophylaxis as primary venous thromboembolism prevention in children. The investigators will perform a United States definitive multicenter phase 3 randomized controlled trial of the low molecular weight heparin dalteparin as primary venous thromboembolism prophylaxis among critically ill adolescents who are classified a priori as high risk based upon the investigators validated risk prediction models.

Full description

This trial will establish definitive evidence on the comparative efficacy and safety of pharmacological thromboprophylaxis with the low molecular weight heparin (LMWH) dalteparin versus standard of care (no pharmacological thromboprophylaxis) for the primary prevention of venous thromboembolism (VTE), including deep vein thrombosis and/or pulmonary embolism) among critically ill adolescents who meet a priori criteria for high risk of hospital-acquired (HA-) VTE. No anticoagulant has been FDA-approved for primary VTE prevention in hospitalized children. In the past two decades, the diagnosis of pediatric hospital-acquired VTE (HA-VTE) in the U.S. has increased 130-200-fold. The investigators have shown that critically-ill adolescents are one the highest risk subpopulations for HA-VTE, with average occurrence rates of 13.2% (range: 6.3-19.8%), and have derived and prospectively validated risk models for HA-VTE in this population. Despite a simultaneously increased risk of bleeding in critically ill adolescents, particularly after surgery or major trauma, an investigator-initiated multicenter phase 2 trial recently led by the investigators group during the COVID-19 pandemic demonstrated the safety of LMWH for primary HA-VTE prevention. To date, risk-stratified phase 3 Randomized Controlled Trials (RCTs) of LMWH thromboprophylaxis as primary HA-VTE prevention in children have not been performed. The investigators will perform a U.S.-based definitive multicenter phase 3 RCT of the LMWH dalteparin versus standard-of-care (SOC), no pharmacological thromboprophylaxis) for VTE prevention among critically ill adolescents at highest a priori risk for HA-VTE applying evidence from the investigators published risk prediction models.

Enrollment

802 estimated patients

Sex

All

Ages

12 to 18 years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Admission Age between 12- 18 years of age
Within 24 hours of pediatric intensive care unit (PICU) admission for enrollment
Presence of a Central Venous Catheter
Anticipated PICU Length of Stay /= 4 days
Presumed or confirmed infection or inflammatory condition

Exclusion criteria

Active treatment for VTE or known VTE present prior to or on pediatric intensive care unit (PICU) admission
Current receipt of an antithrombotic agent excluding unfractionated heparin for vascular catheter patency
Active ISTH-defined clinically relevant bleeding
Surgery in the last 7-days
Major trauma within the last 7-days
Admission for management of congenital heart disease including perioperative management of critical congenital heart disease
Presence of coagulopathy including:
International normalized ratio (INR) 2.0 activated partial thromboplastin time (aPTT) 50 seconds Platelet count 50 x103/mL
Creatinine clearance 30 ml/min/1.73 m2
Known hypersensitivity to heparin or pork products
Laboratory confirmed heparin induced thrombocytopenia
Current pregnancy or lactation,
Presence of an epidural catheter
Prior enrollment in the CRITICAL-Kids-TP Trial