Enoxaparin in Children With Asymptomatic Venous Thrombosis After Pediatric Cardiac Surgery

A Randomized Controlled Trial of Enoxaparin in Children With Asymptomatic Venous Thrombosis After Pediatric Cardiac Surgery

The CATCH-enoxaparin trial is the natural continuation of the CATCH study. It will capitalize on the fact that patients enrolled in the CATCH study will be specifically screened for asymptomatic thromboembolism (TEs) in order to answer important clinical questions.

The investigators propose a randomized controlled trial to address whether, among pediatric patients with congenital heart defects (CHD) recovering from cardiovascular surgery and diagnosed with an asymptomatic venous TE, the use of enoxaparin results in a net therapeutic benefit?

Study Overview

• Status: Withdrawn
• Conditions: Asymptotic Venous Thrombosis
• Intervention / Treatment: Drug: Enoxaparin

Detailed Description

Primary Aim: To address whether, among pediatric patients with congenital heart defects (CHD) recovering from cardiovascular surgery and diagnosed with an asymptomatic venous TE, the use of enoxaparin results in a net therapeutic benefit. We hypothesize that enoxaparin dosed as per age-appropriate algorithms is associated with an increased rate of clot resolution and decreased rate of clot progression/long-term complications in children with CHD and asymptomatic venous TE. Benefits from clot resolution will outweigh the risks associated with the use of enoxaparin resulting in a net therapeutic benefit in favour of enoxaparin use in this context.

Secondary aims of this study are to:

1. To compare the rate of conversion from asymptomatic to symptomatic TE and/or thromboembolic events between treated and untreated patients. Hypothesis: the use of enoxaparin will significantly reduce the rate of conversion from asymptomatic to symptomatic TE.
2. To compare the rate of objective clot progression (or regression) by serial imaging with ultrasound and echocardiography between treated and untreated patients. Hypothesis: the use of enoxaparin will significantly increase the rate of clot regression.
3. To identify factors associated with: TE conversion from asymptomatic to symptomatic, clot resolution and post-thrombotic syndrome in both treated and untreated patients separately. Hypothesis: older children with a more mature coagulation system and those with TEs in superficial vessels (rather than deep/systemic vessels) will have a lower frequency of TE complications.
4. To establish the rate of bleeding complications (both minor and major) for patients on enoxaparin. Hypothesis: we expect major bleeding complications to be present in 2-3% of treated patients and minor bleeding complications to be frequent.

• Study Type: Interventional
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5V1X8
      • The Hospital for Sick Children

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 18 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Pediatric patients with a cardiac defect (acquired or congenital)
2. Recent cardiac surgery (during current hospital admission)3) Presence of a venous clot confirmed by appropriate diagnostic imaging methods associated with either ≥ 25% blood vessel occlusion (clot diameter/vessel diameter) OR is ≥ 3mm in absolute diameter
3. Enrollment in the Heart Centre Biobank Registry
4. Enrollment in the CATCH main study

Exclusion Criteria:

1. Clots associated with any of the following symptoms: swelling, edema, discoloration or high temperature of the affected territory.
2. Clots in a vascular segment/location (arterial clots, intracardiac clots) or with a degree of vessel occlusion which obligatory warrants treatment
3. Prosthetic heart valve
4. Active or previous cancer history
5. Known congenital coagulopathy or thrombophilic disorder
6. Liver failure (AST, ALT or % bilirubin 2x normal)
7. Need for anticoagulation for treatment or prophylaxis for other reasons (e.g. BT shunt, recent thrombosis requiring anticoagulation)
8. Previous documented residual clot within the same vascular territory affected by current asymptomatic clot
9. Increased bleeding risk reflected by severe thrombocytopenia (platelet count <30,000/ml) and/or coagulopathy (INR >4.0 or aPTT >120s)
10. Active bleeding or major bleeding <10 days ago (not surgery related)
11. Previous neurosurgery <14 days ago
12. Uncontrolled severe hypertension (>95th percentile for age)
13. Previous proven diagnosis of heparin-induced-thrombocytopenia (HIT) <100 days ago
14. Absolute contraindication to heparin/LMWH (e.g. severe heparin allergy)
15. Pregnancy or breastfeeding
16. No planned follow-up at The Hospital for Sick Children

While most patients will be identified as part of the CATCH study during the pre-discharge full-body vascular ultrasound, some patients who are not enrolled in CATCH will also be identified if an asymptomatic clot is identified during a clinically indicated radiological study. For those patients who are not already enrolled in the CATCH study and the Heart Centre Biobank Registry, they will be approached and consent will be obtained for those studies prior to enrolment in the CATCH-enoxaparin study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: No-treatment
Experimental: Treatment group; The initial enoxaparin dose will be: 1.75 mg/kg/dose SC q12h for patients ≤ 2 months old or 1 mg/kg/dose SC q12h for patients > 2 months old Adjust the dose of enoxaparin according to the following monogram. Depending on the Enoxaparin Anti-factor Xa level achieved, successive actions are indicated, including whether to hold the next scheduled dose, whether any dose change is indicated and when the next anti-factor Xa level should be drawn.	Drug: Enoxaparin; Lovenox- Enoxaparin; Sanofi-Aventis Canada Inc.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Net therapeutic benefit of enoxaparin	Defined as the between group difference in proportion of patients with negative outcomes (percent clot conversion to symptomatic + percent major bleeding complications)	Events recording from baseline to 18 months post-surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of objective clot size progression (or regression)	This will be determined by serial imaging with ultrasound and frequency of complete clot resolution at the end of the treatment	Up to 18 months post-surgery
Frequency and Risk Factors for conversion from asymptomatic to symptomatic thromboembolism	Defined as the appearance of any of the following symptoms: swelling, edema, discoloration or high temperature of the affected territory	Up to 18months post-surgery
Frequency of and risk factors for post-thrombotic syndrome	Clinical manifestations include varicose veins, edema, skin hyperpigmentation and skin ulcers	18 months after surgery
Frequency of and risk factors for bleeding complications	Minor complications and major episodes defined as cerebral, abdominal, retroperitoneal or pulmonary hemorrhage or any bleeding complications requiring blood transfusions	Up to 18months
Neurodevelopment and health re-lated quality of life	Age appropriate PedsQL® generic module and parent report and Child Health Questionnaire	18 months post-surgery

Collaborators and Investigators

• Sponsor: The Hospital for Sick Children

Study record dates

Study Major Dates

• Study Start: August 1, 2011
• Primary Completion (Anticipated): August 1, 2015
• Study Completion (Anticipated): August 1, 2015

Study Registration Dates

• First Submitted: November 15, 2011
• First Submitted That Met QC Criteria: November 17, 2011
• First Posted (Estimate): November 18, 2011

Study Record Updates

• Last Update Posted (Estimate): August 27, 2013
• Last Update Submitted That Met QC Criteria: August 25, 2013
• Last Verified: August 1, 2013

More Information

Terms related to this study

• Keywords: pediatric; Enoxaparin; pediatric cardiac surgery; asymptotic venous thrombosis
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Embolism and Thrombosis; Thrombosis; Venous Thrombosis; Molecular Mechanisms of Pharmacological Action; Fibrinolytic Agents; Fibrin Modulating Agents; Anticoagulants; Enoxaparin
• Other Study ID Numbers: 1000022022