Pilot Feasibility and Safety of Administering Weight Adjusted Fixed LMWH Dose

NCT02486666 | Unknown Phase 3 DMC FDA Drug

• 1 other identifier: HamiltonHSC
• Study Type: interventional
• Target: 20
• Locations: 2 countries
• Sites: 4

Brief Summary

Background Enoxaparin is a commonly used low molecular weight heparin (LMWH) for the treatment of neonatal and children thrombosis that is monitored with anti-factor Xa (anti-Xa) levels. However, this therapeutic range of anti-Xa (0.5 - 1.0 u/ml) was extrapolated from adult studies. The burden of pain to neonates due to venipunctures and of resources to the health care system also warrants an evidence-based review to assess the utility of monitoring LMWH therapy with anti-Xa levels. Methods/Design This is a prospective pilot, feasibility and safety multicenter, randomized controlled trial to compare the approach of treating thrombosis in neonates and children with enoxaparin using weight adjusted fixed dose to variable dose titrated to maintain a pre-determined anti-Xa range (0.5-1.0 u/mL). We plan to recruit 20 neonates and children over the study period, who will be randomized within their first week of anti-coagulation treatment. Key feasibility outcomes include screening/recruitment ratio, monthly recruitment rate, and completeness of data collection. We will also measure the safety outcome of bleeding as well as comment on efficacy of resolution of thrombosis as a secondary outcome. Discussion The administration of weight adjusted fixed dose of enoxaparin without anti-Xa monitoring has the potential to reduce pain from multiple venipunctures in neonates and children as well as resources used in their already complex care. The results of the FiXET trial will set the framework for a larger multicenter randomized controlled trial to compare the efficacy of administering enoxaparin to neonates and children without monitoring to the current conventional approach of routine monitoring with anti-Xa levels.

Conditions

Venous Thromboembolism

Keywords

Enoxaparin; thrombosis; neonate; children; RCT

Outcome Measures

Primary Outcomes (2)

• Feasibility of recruiting at least 5 subjects over the study period per center

  * Number of Participants from each participating center * Rate of recruitment per approaching * Rate of completed data collection and follow-up per all recruited subjects These variables will be combined to reflect the feasibility of trial recruitment

  12 - 24 months

• Safety of administering a weight adjusted fixed dose of enoxaparin to neonates and children with thrombosis

  \- Percentage of subjects removed from the study due to 1) low or high anti Xa levels or 2) major bleeding

  12 - 24months

Secondary Outcomes (2)

• Efficacy in resolution of thrombosis

  12-24 months

• Safety of anticoagulation

  12-24 months

Study Arms (2)

Experimental Arm

EXPERIMENTAL

Experimental Arm:patients will not have any dose titration regardless of anti-Xa level. Premature neonates will receive enoxaparin 2.0 mg/kg/dose rounded to nearest whole mg twice daily, while term neonates will receive enoxaparin 1.7 mg/kg/dose rounded to nearest whole mg twice daily. Children≥1 month corrected age will receive 1.5 mg/kg/dose twice daily (maybe rounded +/- 10% for convenience of dosing) while children≥2 month corrected age will receive 1.0 mg/kg/dose twice daily (maybe rounded +/- 10% for convenience of dosing).

Drug: Enoxaparin

Control Arm

OTHER

Control Arm: patients who will have dose titration based on anti-Xa levels to maintain a therapeutic range of 0.5-1.0 u/mL (standard of care).

Drug: Enoxaparin

Interventions

Enoxaparin DRUG

WEIGHT ADJUSTED FiXED DOSE OF LOW MOLECULAR WEIGHT HEPARIN (ENOXAPARIN) TO NEONATES AND CHILDREN WITH THROMBOSIS (FiXET)

Also known as: Enoxaparin sodium

Control Arm; Experimental Arm

Eligibility Criteria

• Age: Up to 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Birth to under 18 years of age at the diagnosis of thrombosis event
• Diagnosis of deep vein thrombosis confirmed by either venography or ultrasound, pulmonary embolism confirmed by ventilation perfusion scan or spiral CT scan or pulmonary angiogram, clinically stable cerebral sinovenous thrombosis confirmed with magnetic resonance imaging, or cardiac thrombosis diagnosed by echocardiogram.
• The treating team has decided to initiate anti-coagulation therapy

You may not qualify if:

• Platelet count \< 50x109/L;
• Hemorrhage or high risk of bleeding with the use of anticoagulation therapy;
• Creatinine \> 1.5x upper limit of normal;
• Liver dysfunction associated with coagulopathy leading to a clinically relevant bleeding risk;
• Documented history of heparin induced thrombocytopenia;
• Known contraindication to heparin

Sponsors & Collaborators

• Hamilton Health Sciences Corporation: lead
• IWK Health Centre: collaborator
• Children's Hospital of Philadelphia: collaborator
• Children's Hospital of Eastern Ontario: collaborator

Study Sites (4)

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

RECRUITING

IWK Health Center

Halifax, Nova Scotia, B3K 6R8, Canada

RECRUITING

HHSC/McMaster Children's Hospital

Hamilton, Ontario, L8N3Z5, Canada

RECRUITING

Children's Hospital of Eastern Ontario

Ottawa, Ontario, K1H 8L1, Canada

NOT YET RECRUITING

MeSH Terms

Conditions

Venous Thromboembolism; Thrombosis

Interventions

Enoxaparin; enoxaparin sodium

Condition Hierarchy (Ancestors)

Thromboembolism; Embolism and Thrombosis; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

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

Study Officials

• Mihir Bhatt, MD

  HHSC/McMaster Children's Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Wenli Xie, MSc, CCRC

CONTACT

905-521-2100; xiew@mcmaster.ca

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Pilot study

Study Record Dates

• First Submitted: May 14, 2015
• First Posted: July 1, 2015
• Study Start: March 1, 2016
• Primary Completion: December 1, 2022
• Study Completion: December 1, 2022
• Last Updated: October 15, 2021

Record last verified: 2021-10

Data Sharing

• IPD Sharing: Will not share

Locations

CA (3); US (1)