A Pilot Feasibility And Safety Multicenter Trial Of Administering Weight Adjusted Fixed Dose Of Low Molecular Weight Heparin (Enoxaparin) To Neonates and Children With Thrombosis (FiXET)

1. Scientific Rationale 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 and children 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. This FiXET trial is 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.

1.1 Potential Risk and Benefits 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 care. The results of the FiXET trial will provide preliminary clinical data regarding the feasibility and safety of this approach to anticoagulation treatment in neonates and children. It will also provide a preliminary idea about the efficacy of such an approach. This trial, if successful, will set groundwork 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. 2. Study Objectives The aim of this trial is to determine the feasibility and safety of doing a randomized control 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). 3. Eligibility Criteria Four or more tertiary hospitals will participate in this trial. We plan to recruit a total of 20 patients based on the following protocol-defined inclusion and exclusion criteria. 4. Study Design FiXET trial is a prospective pilot, feasibility and safety multicenter, randomized controlled trial. Recruitment will start following institutional REB approval. This will occur over 1year per centre and may take up to 2 years. Analysis and dissemination will occur after this period of time.

4.1 Study Endpoints

Primary Objective The primary outcome of this trial is to assess feasibility and safety, as defined below, of administering a weight adjusted fixed dose of enoxaparin to neonates and children with thrombosis.

Feasibility criteria

• At least 5 subjects can be recruited in each participating centre over the study period
• At least 50% of all approached patients can be recruited
• Complete data collection and follow-up of at least 90% of all recruited subjects