Clinical trial NCT01474902: Enoxaparin in Children With Asymptomatic Venous Thrombosis After Pediatric Cardiac Surgery
Official title: A Randomized Controlled Trial of Enoxaparin in Children With Asymptomatic Venous Thrombosis After Pediatric Cardiac Surgery
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE3
Conditions: Asymptotic Venous Thrombosis
Keywords: pediatric
asymptotic venous thrombosis
Enoxaparin
pediatric cardiac surgery
Lead sponsor: The Hospital for Sick Children
Sponsor class: OTHER
First posted: 2011-11-18
Enrollment: 0
Sex: ALL
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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?

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Net therapeutic benefit of enoxaparin
timeFrame: Events recording from baseline to 18 months post-surgery
Secondary outcomes:
measure: Rate of objective clot size progression (or regression)
timeFrame: Up to 18 months post-surgery
measure: Frequency and Risk Factors for conversion from asymptomatic to symptomatic thromboembolism
timeFrame: Up to 18months post-surgery
measure: Frequency of and risk factors for post-thrombotic syndrome
timeFrame: 18 months after surgery
measure: Frequency of and risk factors for bleeding complications
timeFrame: Up to 18months
measure: Neurodevelopment and health re-lated quality of life
timeFrame: 18 months post-surgery
Other outcomes:
Locations:
city: Toronto
country: Canada
facility: The Hospital for Sick Children
state: Ontario
Study officials:
affiliation: The Hospital for Sick Children
name: Brian W McCrindle, MD
role: PRINCIPAL_INVESTIGATOR
References: