Clinical trial NCT06628778: Collaborative Risk-stratified Investigation in Teen Inpatients With Critical Illness: Anticoagulation With LMWH in Kids for ThromboProphylaxis (CRITICAL-Kids-TP)
Official title: Collaborative Risk-stratified Investigation in Teen Inpatients With Critical Illness: Anticoagulation With LMWH in Kids for ThromboProphylaxis (CRITICAL-Kids-TP)
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE3
Conditions: Venous Thromboembolism (VTE)
Keywords: pediatric
adolescent
critical illness
thromboprophylaxis
Lead sponsor: Johns Hopkins All Children's Hospital
Sponsor class: OTHER
Collaborators: name: University of California, San Diego
First posted: 2024-10-08
Enrollment: 802
Sex: ALL
Minimum age (years): 12
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: PROBE study design, Randomized allocation 2:1 (Intervention:Standard of care) of dalteparin thromboprophylaxis versus standard-of-care (i.e., no pharmacological thromboprophylaxis). Analytic study populations will be modified intent-to-treat, per-protocol, and safety populations
Primary purpose: PREVENTION

Brief summary: 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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Risk (i.e., cumulative incidence) of Symptomatic venous thromboembolism
timeFrame: From randomization through discharge from the pediatric intensive care unit, approximately 1-2 weeks
measure: Risk (i.e., cumulative incidence) of Clinically relevant bleeding
timeFrame: From randomization through discharge from the pediatric intensive care unit, approximately 1-2 weeks
Secondary outcomes:
measure: Net Clinical Benefit - Modelled Attributable Risk Difference in HA-VTE (Efficacy) by Attributable Risk Difference in clinically relevant bleeding (Safety)
timeFrame: From randomization through discharge from the pediatric intensive care unit, approximately 1-2 weeks
measure: Risk (i.e. cumulative incidence) of symptomatic venous thromboembolism
timeFrame: From randomization through 30-days post discharge from the pediatric intensive care unit
measure: Risk (i.e. cumulative incidence) of clinically relevant bleeding
timeFrame: From randomization through 30-days post discharge from the pediatric intensive care unit
measure: Serious adverse events
timeFrame: From randomization through 30-days post discharge from the pediatric intensive care unit
Other outcomes:
Locations:
city: Saint Petersburg
country: United States
facility: Johns Hopkins All Children"s Hospital
state: Florida
Study officials:
affiliation: Johns Hopkins All Children's Hospital
name: Anthony Sochet, MD, MSc
role: PRINCIPAL_INVESTIGATOR
References: