Catheter-Related Early Thromboprophylaxis With Enoxaparin Studies (CRETE)

June 4, 2026 updated by: E. Vincent S. Faustino, Yale University

Age-dependent Heterogeneity in the Efficacy of Prophylaxis With Enoxaparin Against Catheter-associated Thrombosis in Critically Ill Children

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
258

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

Study Locations

  • United States
    • Alabama
      • Birmingham, Alabama, United States, 35233
        • Recruiting
        • Children's of Alabama
        • Principal Investigator:
          • Michele Kong, MD
        • Contact:
    • Arkansas
      • Little Rock, Arkansas, United States, 72202
        • Recruiting
        • Arkansas Children's Hospital
        • Contact:
        • Principal Investigator:
          • Erin Bennett, MD
    • Colorado
      • Aurora, Colorado, United States, 80045
    • Connecticut
      • New Haven, Connecticut, United States, 06520
        • Recruiting
        • Yale-New Haven Children's Hospital
        • Contact:
          • E. Vincent Faustino, MD, MHS
        • Principal Investigator:
          • Vincent Faustino, MD, MHS
        • Contact:
    • Florida
      • Gainesville, Florida, United States, 32610
        • Recruiting
        • University of Florida -UF Health
        • Contact:
        • Principal Investigator:
          • Jose Cardenas, MD
      • St. Petersburg, Florida, United States, 33701
        • Recruiting
        • Johns Hopkins All Children's
        • Principal Investigator:
          • Anthony Sochet, MD
        • Contact:
    • Illinois
      • Peoria, Illinois, United States, 61637
        • Recruiting
        • Children's Hospital of Illinois at OSF Saint Francis Medical Center
        • Contact:
        • Principal Investigator:
          • Madhuradhar Chegondi, MD
    • Iowa
      • Iowa City, Iowa, United States, 52242
        • Recruiting
        • Stead Family Children's Hospital
        • Contact:
        • Principal Investigator:
          • Mahil Rao
    • Missouri
      • St Louis, Missouri, United States, 63110
        • Recruiting
        • Children's Hospital St. Louis
        • Contact:
        • Principal Investigator:
          • Michael Kramer, MD
    • New York
      • New York, New York, United States, 10065
        • Recruiting
        • New York Presbyterian Hospital
        • Principal Investigator:
          • Marianne Nellis, MD
        • Contact:
      • New York, New York, United States, 10016
        • Recruiting
        • Hassenfeld Children's Hospital
        • Contact:
        • Principal Investigator:
          • Michelle Ramirez, MD
      • Rochester, New York, United States, 14642
      • Valhalla, New York, United States, 10595
        • Recruiting
        • Maria Fareri Children's Hospital
        • Principal Investigator:
          • Matthew Pinto, MD
        • Contact:
    • Ohio
      • Cleveland, Ohio, United States, 44106
      • Columbus, Ohio, United States, 43205
        • Withdrawn
        • Nationwide Children's Hospital
    • Oklahoma
      • Oklahoma City, Oklahoma, United States, 73104
        • Recruiting
        • University of Oklahoma
        • Contact:
        • Principal Investigator:
          • Christine Allen, MD
    • Pennsylvania
      • Hershey, Pennsylvania, United States, 17033
        • Recruiting
        • Penn State Hershey Children's Hospital
        • Contact:
        • Principal Investigator:
          • Elizabeth Kerris, MD
      • Philadelphia, Pennsylvania, United States, 19104
        • Recruiting
        • Children's Hospital of Philadelphia
        • Principal Investigator:
          • Christine Glau, MD
        • Contact:
    • Texas
    • Virginia
      • Richmond, Virginia, United States, 23219
        • Withdrawn
        • Children's Hospital of Richmond
    • Wisconsin
      • Milwaukee, Wisconsin, United States, 53226
        • Recruiting
        • Children's Hospital Wisconsin
        • Contact:
        • Principal Investigator:
          • Hilary Schreiber, MD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

No older than 17 years (Child)

Accepts Healthy Volunteers

No

Description

Inclusion criteria

  1. >36 weeks corrected gestational to <17 years old
  2. <24 hours after insertion of an untunneled CVC
  3. CVC inserted in the internal jugular or femoral vein

Exclusion criteria

  1. Radiologic diagnosis of CADVT in the site of insertion in prior 6 weeks
  2. Currently receiving an antithrombotic agent, e.g., LMWH, UFH, warfarin and aspirin, but not UFH at dose to maintain patency of a vascular catheter
  3. 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
  4. Surgery in the prior 7 days
  5. Major trauma in the prior 7 days
  6. Presence of coagulopathy, i.e., INR >2.0, aPTT >50 seconds or platelet count <50 x 10^3/mcL
  7. Presence of renal failure, i.e., creatinine clearance <30 mL/min/1.73 m2
  8. Known hypersensitivity to heparin or pork products
  9. Laboratory confirmed HIT
  10. Current pregnancy or lactation
  11. Presence of an epidural catheter
  12. Limitation of care
  13. Previous enrollment in the CRETE Studies

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Enoxaparin (Older Children Prophylactic)
Prophylactic dose of enoxaparin for older children 1-17 years old.
Drug: Enoxaparin
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.
Other Names:
  • Clexane
  • Lovenox
No Intervention: Control (Older Children)
Usual care without placebo for older children 1-17 years old.
Experimental: Enoxaparin (Infants Therapeutic High Anti-Xa Target)
Therapeutic dose of enoxaparin for infants <1 year old with anti-Xa target of >0.5-1 IU/mL.
Drug: Enoxaparin
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.
Other Names:
  • Clexane
  • Lovenox
Experimental: Enoxaparin (Infants Therapeutic Low Anti-Xa Target)
Therapeutic dose of enoxaparin for infants <1 year old with anti-Xa target of 0.2-0.5 IU/mL.
Drug: Enoxaparin
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.
Other Names:
  • Clexane
  • Lovenox
No Intervention: Control (Infants)
Usual care without placebo for infants <1 year old.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Number of children with CADVT
Time Frame: 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.
Up to removal of CVC (maximum of 28 days)

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Number of children with any VTE
Time Frame: Up to removal of CVC (maximum of 28 days)
Thrombus in the deep vein of any extremity or PE that is confirmed radiologically
Up to removal of CVC (maximum of 28 days)
Number of children with clinically apparent CADVT
Time Frame: Up to removal of CVC (maximum of 28 days)
Any CADVT, except one that is only diagnosed with the systematic ultrasonographic surveillance.
Up to removal of CVC (maximum of 28 days)
Number of children with clinically apparent VTE
Time Frame: Up to removal of CVC (maximum of 28 days)
Any VTE, except one that is only diagnosed with the systematic ultrasonographic surveillance.
Up to removal of CVC (maximum of 28 days)
Number of children with clinically relevant bleeding
Time Frame: 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.
Maximum of 36 hours after the last dose of enoxaparin
Number of children with any bleeding
Time Frame: Maximum of 36 hours after the last dose of enoxaparin
Any overt or macroscopic evidence of bleeding.
Maximum of 36 hours after the last dose of enoxaparin
Number of children with heparin-induced thrombocytopenia
Time Frame: 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.
Maximum of 36 hours after the last dose of enoxaparin

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Yale University

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Children's Hospital of Philadelphia
University of Iowa
Children's Hospital Colorado
University of Oklahoma
Medical College of Wisconsin
Nationwide Children's Hospital
Penn State University
New York Presbyterian Hospital
Johns Hopkins All Children's Hospital
Children's of Alabama
BJC HealthCare
Golisano Children's Hospital
Maria Fareri Children's Hospital
Hassenfeld Children's Hospital
Children's Hospital of Illinois at Peoria

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: E. Vincent Faustino, MD, MHS, Associate Professor of Pediatrics, Yale School of Medicine

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
May 11, 2022

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
April 30, 2027

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
August 31, 2027

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
June 7, 2021

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 7, 2021

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
June 11, 2021

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
June 8, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 4, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
June 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 2000030683
  • 1R01HD106326-01 (U.S. NIH Grant/Contract)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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