Catheter-Related Early Thromboprophylaxis With Enoxaparin (CRETE) Trial

NCT03003390 | Terminated Phase 2 Results DMC FDA Drug

• 2 other identifiers: 13020115061R21HD089131-01A1
• Study Type: interventional
• Target: 51
• Locations: 1 country
• Sites: 6

Brief Summary

The purpose of this phase 2a, multi-center, randomized controlled study, is to explore the efficacy of early prophylaxis against catheter-associated deep venous thrombosis (CADVT) in critically ill children.

Conditions

Deep Venous Thrombosis

Keywords

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

Outcome Measures

Primary Outcomes (2)

• Number of Participants With Central Venous Catheter (CVC)- Associated Deep Vein Thrombosis (DVT)

  Thrombus in the central vein where the CVC was inserted that is clinically suspected then confirmed radiologically, an incidental radiologic finding, or diagnosed with the study-related active surveillance ultrasound

  Up to removal of CVC, an average of 6 days

• Endogenous Thrombin Potential

  An established measure of coagulation status and is the best method to measure thrombin generation. It directly measures the amount of thrombin generation over time capturing the effects of natural (i.e., subject's coagulation status) and pharmacological (e.g., enoxaparin) pro- and anticoagulants. Endogenous thrombin potential is measured using thrombin generation assay.

  Day of, day after and day 4 after insertion of the CVC

Secondary Outcomes (11)

• Number With Other Thromboembolic Events

  Up to removal of CVC, an average of 6 days

• Length of Stay in the Pediatric Intensive Care Unit in Days

  Up to day of discharge from the pediatric intensive care unit, an average of 10 days

• Length of Stay in the Hospital

  Up to day of discharge from the hospital, an average of 18 days

• Number With Clinically Relevant Bleeding

  Up to 30 hours after the last enoxaparin dose

• Number With Laboratory Confirmed Heparin-induced Thrombocytopenia

  Up to removal of CVC, an average of 6 days

Study Arms (2)

Prophylaxis with enoxaparin

EXPERIMENTAL

A clinical nurse will administer enoxaparin subcutaneously \<24 hours after insertion of the central venous catheter and then give enoxaparin subcutaneously every 12 hours until the removal of the catheter.

Drug: Enoxaparin

Control arm

NO INTERVENTION

Participants randomized to the control arm will receive no 'placebo' intervention.

Interventions

Enoxaparin DRUG

The clinical nurse will give enoxaparin subcutaneously every 12 hours at the currently used starting dose of 0.75 mg/kg for children ≤2 months old or 0.5 mg/kg (maximum of 40 mg) for older children. The 1st dose will be given \<24 hours after insertion of the catheter. Doses will be adjusted to target an anti-Xa level of 0.2-0.5 IU/mL.

Also known as: Lovenox

Prophylaxis with enoxaparin

Eligibility Criteria

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

You may qualify if:

• Untunneled CVC inserted in the internal jugular or femoral vein within the past 24 hours
• Child anticipated to stay in the pediatric intensive care unit ≥48 hours
• CVC anticipated to be required for ≥24 hours
• \>36 weeks corrected gestational age to \<18 years old

You may not qualify if:

• Coagulopathy (i.e., international normalized ratio \>2.0, activated partial thromboplastin time \>50 seconds or platelet count \<50,000/mm3)
• Known bleeding disorder
• Clinically relevant bleeding as defined by the International Society on Thrombosis and Hemostasis (i.e., Hb decreased ≥2 g/dl in 24 hours, required medical or surgical intervention to restore hemostasis, or in a critical organ system \[i.e., retroperitoneum, pulmonary, intracranial or central nervous system\])
• \<60 days from a clinically relevant bleeding as defined above
• \<7 days after trauma or surgery
• Anticipated surgery within 48 hours after insertion of the CVC
• Renal failure (i.e., creatinine clearance \<30 mL/min)
• Presence of epidural catheter
• Currently taking an antithrombotic agent (e.g., low molecular weight heparin (LMWH), unfractionated heparin (UFH) at therapeutic doses, Coumadin or aspirin)
• Radiologically documented DVT at the site of insertion of the CVC in the previous 6 weeks
• Known hypersensitivity to heparin or its components, including pork products
• History of heparin-induced thrombocytopenia (HIT) (i.e., positive serotonin release assay)
• Currently pregnant
• Currently lactating
• Prior enrollment in the study

Sponsors & Collaborators

• Yale University: lead
• St. Louis Children's Hospital: collaborator
• Dell Children's Medical Center of Central Texas: collaborator
• Children's Hospital and Health System Foundation, Wisconsin: collaborator
• Weill Medical College of Cornell University: collaborator
• Maria Fareri Children's Hospital: collaborator
• University of Rochester: collaborator
• Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD): collaborator

Study Sites (6)

Yale University Yale New Haven Health

New Haven, Connecticut, 06520, United States

Location

Saint Louis Children's Hospital-Washington University School of Medicine-

St Louis, Missouri, 63110, United States

Location

Weill Cornell Medicine

New York, New York, 10065, United States

Location

University of Rochester Medical Center-Golisano Children's Hospital-

Rochester, New York, 14642, United States

Location

Maria Fareri Children's Hospital

Valhalla, New York, 10595, United States

Location

Children's Hospital of Wisconsin/Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

Related Publications (2)

• Faustino EVS, Raffini LJ, Hanson SJ, Cholette JM, Pinto MG, Li S, Kandil SB, Nellis ME, Shabanova V, Silva CT, Tala JA, McPartland T, Spinella PC; for the CRETE Trial Investigators and the Pediatric Critical Care Blood Research Network (BloodNet) of the Pediatric Acute Lung Injury and Sepsis Investigators Network (PALISI); CRETE Trial Investigators: Clinical Coordinating Center:; and; Data Coordinating Center:; and; Outcomes Adjudication Committee:; and; Data and Safety Monitoring Board:; and; Independent Safety Monitor:; and; Children's Hospital Wisconsin:; and; Dell Children's Medical Center:; and; Maria Fareri Children's Hospital:; and; St. Louis Children's Hospital:; and; University of Rochester Golisano Children's Hospital:; and; Weill Cornell Medical Center:; and; and Yale-New Haven Children's Hospital:; and; for the CRETE Trial Investigators and the Pediatric Critical Care Blood Research Network (BloodNet) of the Pediatric Acute Lung Injury and Sepsis Investigators Network (PALISI) and CRETE Trial Investigators: Clinical Coordinating Center: and and and Data Coordinating Center: and and and Outcomes Adjudication Committee: and and and Data and Safety Monitoring Board: and and and Independent Safety Monitor: and and and Children's Hospital Wisconsin: and and and Dell Children's Medical Center: and and and Maria Fareri Children's Hospital: and and and St. Louis Children's Hospital: and and and University of Rochester Golisano Children's Hospital: and and and Weill Cornell Medical Center: and and and and Yale-New Haven Children's Hospital: and and. Age-Dependent Heterogeneity in the Efficacy of Prophylaxis With Enoxaparin Against Catheter-Associated Thrombosis in Critically Ill Children: A Post Hoc Analysis of a Bayesian Phase 2b Randomized Clinical Trial. Crit Care Med. 2021 Apr 1;49(4):e369-e380. doi: 10.1097/CCM.0000000000004848.

  PMID: 33566465 DERIVED

• Faustino EVS, Shabanova V, Raffini LJ, Kandil SB, Li S, Pinto MG, Cholette JM, Hanson SJ, Nellis ME, Silva CT, Chima R, Sharathkumar A, Thomas KA, McPartland T, Tala JA, Spinella PC; CRETE Trial Investigators and the Pediatric Critical Care Blood Research Network (BloodNet) of the Pediatric Acute Lung Injury and Sepsis Investigators Network (PALISI). Efficacy of Early Prophylaxis Against Catheter-Associated Thrombosis in Critically Ill Children: A Bayesian Phase 2b Randomized Clinical Trial. Crit Care Med. 2021 Mar 1;49(3):e235-e246. doi: 10.1097/CCM.0000000000004784.

  PMID: 33372745 DERIVED

MeSH Terms

Conditions

Venous Thrombosis; Critical Illness; Venous Thromboembolism

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

Results Point of Contact

• Title: Dr. E. Vincent S Faustino
• Organization: Yale University

vince.faustino@yale.edu

203-785-4651

Study Officials

• E. Vincent S Faustino, MD, MHS

  Associate Professor of Pediatrics, Yale School of Medicine

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Eligible subjects will be randomized 1:1 to treatment or control.

Study Record Dates

• First Submitted: December 19, 2016
• First Posted: December 28, 2016
• Study Start: April 5, 2017
• Primary Completion: August 16, 2019
• Study Completion: August 16, 2019
• Last Updated: July 13, 2020
• Results First Posted: July 13, 2020

Record last verified: 2020-03

Locations

US (6)