Catheter-Related Early Thromboprophylaxis With Enoxaparin Studies

NCT04924322 | Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: 20000306831R01HD106326-01
• Study Type: interventional
• Target: 258
• Locations: 1 country
• Sites: 22

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.

Conditions

Deep Venous Thrombosis

Keywords

child; critical illness; venous thromboembolism; enoxaparin; thrombin generation; bleed

Outcome Measures

Primary Outcomes (1)

• Number of children with CADVT

  Thrombus in the central vein where the CVC was inserted that is diagnosed with systematic ultrasonographic surveillance.

  Up to removal of CVC (maximum of 28 days)

Secondary Outcomes (6)

• Number of children with any VTE

  Up to removal of CVC (maximum of 28 days)

• Number of children with clinically apparent CADVT

  Up to removal of CVC (maximum of 28 days)

• Number of children with clinically apparent VTE

  Up to removal of CVC (maximum of 28 days)

• Number of children with clinically relevant bleeding

  Maximum of 36 hours after the last dose of enoxaparin

• Number of children with any bleeding

  Maximum of 36 hours after the last dose of enoxaparin

Study Arms (5)

Enoxaparin (Older Children Prophylactic)

EXPERIMENTAL

Prophylactic dose of enoxaparin for older children 1-17 years old.

Drug: Enoxaparin

Control (Older Children)

NO INTERVENTION

Usual care without placebo for older children 1-17 years old.

Enoxaparin (Infants Therapeutic High Anti-Xa Target)

EXPERIMENTAL

Therapeutic dose of enoxaparin for infants \<1 year old with anti-Xa target of \>0.5-1 IU/mL.

Drug: Enoxaparin

Enoxaparin (Infants Therapeutic Low Anti-Xa Target)

EXPERIMENTAL

Therapeutic dose of enoxaparin for infants \<1 year old with anti-Xa target of 0.2-0.5 IU/mL.

Drug: Enoxaparin

Control (Infants)

NO INTERVENTION

Usual care without placebo for infants \<1 year old.

Interventions

Enoxaparin DRUG

Enoxaparin is a LMWH produced from UFH that exerts its anticoagulant effects by binding to and inducing a conformational change in antithrombin to accelerate the inactivation of factor Xa and thrombin. Age-specified dose of enoxaparin will be administered within 24 hours after insertion of the CVC with the dose subsequently adjusted to pre-specified anti-Xa target.

Also known as: Lovenox, Clexane

Enoxaparin (Infants Therapeutic High Anti-Xa Target); Enoxaparin (Infants Therapeutic Low Anti-Xa Target); Enoxaparin (Older Children Prophylactic)

Eligibility Criteria

• Age: Up to 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• \>36 weeks corrected gestational to \<17 years old
• \<24 hours after insertion of an untunneled CVC
• CVC inserted in the internal jugular or femoral vein

You may not qualify if:

• Radiologic diagnosis of CADVT in the site of insertion in prior 6 weeks
• Currently receiving an antithrombotic agent, e.g., LMWH, UFH, warfarin and aspirin, but not UFH at dose to maintain patency of a vascular catheter
• Presence of clinically relevant bleeding, i.e., hemoglobin decreased ≥2 g/dl in 24 hours, required medical or surgical intervention to restore hemostasis, or in the retroperitoneum, pulmonary, intracranial or central nervous system, in the prior 60 days
• Surgery in the prior 7 days
• Major trauma in the prior 7 days
• Presence of coagulopathy, i.e., INR \>2.0, aPTT \>50 seconds or platelet count \<50 x 10\^3/mcL
• Presence of renal failure, i.e., creatinine clearance \<30 mL/min/1.73 m2
• Known hypersensitivity to heparin or pork products
• Laboratory confirmed HIT
• Current pregnancy or lactation
• Presence of an epidural catheter
• Limitation of care
• Previous enrollment in the CRETE Studies

Sponsors & Collaborators

• Yale University: lead
• Children's Hospital Colorado: collaborator
• Children's Hospital of Philadelphia: collaborator
• BJC HealthCare: collaborator
• Medical College of Wisconsin: collaborator
• Children's of Alabama: collaborator
• Golisano Children's Hospital: collaborator
• Maria Fareri Children's Hospital: collaborator
• Nationwide Children's Hospital: collaborator
• New York Presbyterian Hospital: collaborator
• Penn State University: collaborator
• University of Iowa: collaborator
• Johns Hopkins All Children's Hospital: collaborator
• University of Oklahoma: collaborator
• Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD): collaborator
• Children's Hospital of Illinois OSF Saint Francis Medical Center: collaborator
• Hassenfeld Children's Hospital: collaborator

Study Sites (22)

Children's of Alabama

Birmingham, Alabama, 35233, United States

RECRUITING

Arkansas Children's Hospital

Little Rock, Arkansas, 72202, United States

RECRUITING

Children's Hospital Colorado

Aurora, Colorado, 80045, United States

RECRUITING

Yale-New Haven Children's Hospital

New Haven, Connecticut, 06520, United States

RECRUITING

University of Florida -UF Health

Gainesville, Florida, 32610, United States

RECRUITING

Johns Hopkins All Children's

St. Petersburg, Florida, 33701, United States

RECRUITING

Children's Hospital of Illinois at OSF Saint Francis Medical Center

Peoria, Illinois, 61637, United States

RECRUITING

Stead Family Children's Hospital

Iowa City, Iowa, 52242, United States

RECRUITING

Children's Hospital St. Louis

St Louis, Missouri, 63110, United States

RECRUITING

Hassenfeld Children's Hospital

New York, New York, 10016, United States

RECRUITING

New York Presbyterian Hospital

New York, New York, 10065, United States

RECRUITING

Golisano Children's Hospital

Rochester, New York, 14642, United States

RECRUITING

Maria Fareri Children's Hospital

Valhalla, New York, 10595, United States

RECRUITING

UH Rainbow Babies & Children's Hospital

Cleveland, Ohio, 44106, United States

RECRUITING

Nationwide Children's Hospital

Columbus, Ohio, 43205, United States

WITHDRAWN

University of Oklahoma

Oklahoma City, Oklahoma, 73104, United States

RECRUITING

Penn State Hershey Children's Hospital

Hershey, Pennsylvania, 17033, United States

RECRUITING

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

RECRUITING

Dell Children's Medical Canter

Austin, Texas, 78723, United States

RECRUITING

UTSW Medical Center; Children's Medical Center of Dallas

Dallas, Texas, 75235, United States

RECRUITING

Children's Hospital of Richmond

Richmond, Virginia, 23219, United States

WITHDRAWN

Children's Hospital Wisconsin

Milwaukee, Wisconsin, 53226, United States

RECRUITING

Related Publications (1)

• Faustino EVS, Kandil SB, Leroue MK, Sochet AA, Kong M, Cholette JM, Nellis ME, Pinto MG, Chegondi M, Ramirez M, Schreiber H, Kerris EWJ, Glau CL, Kolmar A, Muisyo TM, Sharathkumar A, Polikoff L, Silva CT, Ehrlich L, Navarro OM, Spinella PC, Raffini L, Taylor SN, McPartland T, Shabanova V; Catheter-Related Early Thromboprophylaxis with Enoxaparin (CRETE) Studies Investigators and the Pediatric Critical Care Blood Research Network (BloodNet) of the Pediatric Acute Lung Injury and Sepsis Investigators Network (PALISI). Protocol for the Catheter-Related Early Thromboprophylaxis With Enoxaparin (CRETE) Studies. Pediatr Crit Care Med. 2025 Jan 1;26(1):e95-e105. doi: 10.1097/PCC.0000000000003648. Epub 2024 Nov 20.

  PMID: 39560771 DERIVED

MeSH Terms

Conditions

Venous Thrombosis; Critical Illness; Venous Thromboembolism; Hemorrhage

Interventions

Enoxaparin

Condition Hierarchy (Ancestors)

Thrombosis; Embolism and Thrombosis; Vascular Diseases; Cardiovascular Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Thromboembolism

Intervention Hierarchy (Ancestors)

Heparin, Low-Molecular-Weight; Heparin; Glycosaminoglycans; Polysaccharides; Carbohydrates

Study Officials

• E. Vincent Faustino, MD, MHS

  Associate Professor of Pediatrics, Yale School of Medicine

  PRINCIPAL INVESTIGATOR

Central Study Contacts

E. Vincent Faustino, MD, MHS

CONTACT

203-785-4651; vince.faustino@yale.edu

Tara McPartland, MSW, MPH

CONTACT

203-737-7173; tara.mcpartland@yale.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: The CRETE Studies are open-label with blinded endpoint. Systematic ultrasonographic assessment will be performed with the images blindly and centrally adjudicated.
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Pediatrics (Critical Care)

Model Details: Older children 1-17 years old and infants \<1 year old will be randomized separately. Older children will be randomized 2:1 to prophylactic dose of enoxaparin or control stratified by age. Infants will be randomized 1:1:1 to therapeutic dose of enoxaparin with high or low anti-Xa target or control stratified by age.

Study Record Dates

• First Submitted: June 7, 2021
• First Posted: June 11, 2021
• Study Start: May 11, 2022
• Primary Completion: April 30, 2026
• Study Completion (Estimated): July 31, 2026
• Last Updated: June 11, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (22)