Philadelphia, Pennsylvania 19104


Purpose:

Background Enoxaparin is a commonly used low molecular weight heparin (LMWH) for the treatment of neonatal 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 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 over the study period, who will be randomized prior to their first anti-Xa level being resulted. 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 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 without monitoring to the current conventional approach of routine monitoring with anti-Xa levels.


Study summary:

1. Scientific Rationale Enoxaparin is a commonly used low molecular weight heparin (LMWH) for the treatment of neonatal 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. This FiXET trial is to compare the approach of treating thrombosis in neonates 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 over the study period, who will be randomized prior to their first anti-Xa level being resulted. 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 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. 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 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 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 The neonatal intensive care units of 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 6 months per center and may take up to 1 year. 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 with thrombosis. Feasibility criteria - At least 5 subjects can be recruited in each participating center 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 Safety criteria - No more than 20% of subjects are removed from the study due to 1) low or high anti-Xa levels, or 2) major bleeding Major bleeding will be defined as (i) fatal bleeding; (ii) clinically overt bleeding resulting associated with a decrease in hemoglobin of 20 g/L (2 g/dL) in a 24 hour period; (iii) bleeding into a critical organ (intracranial, pulmonary or retroperitoneal); or bleeding requiring surgical intervention [17]. Minor bleeding will be defined as any overt or macroscopic evidence of bleeding that does not fulfill criteria for major bleeding [17]. Secondary Objective Secondary outcome measures include 1) efficacy in resolution of thrombosis; 2) mean anti-Xa levels; 3) number of enoxaparin dose adjustments required in the control arm; and 4) number of venipuncture attempts for blood sampling in patients. 5. Expected Duration of Participant Participation The duration of enoxaparin therapy will be 6 weeks to 6 months at the discretion of the treating physician.


Criteria:

Inclusion Criteria - Premature (<36 completed weeks gestational age, 0-60 days of corrected age) and term (≥37 completed weeks GA, 0-60 days of corrected age) neonates; - 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, or cardiac thrombosis diagnosed by echocardiogram. - The treating team has decided to initiate anti-coagulation therapy Exclusion Criteria - Cerebral sinovenous thrombosis; - 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


NCT ID:

NCT02486666


Primary Contact:

Principal Investigator
Mihir Bhatt, MD
HHSC/McMaster Children's Hospital

Korinne Hamilton, MSc, CCRA
Phone: 905-521-2100 ext. 76054
Email: hamiltonko@hhsc.ca


Backup Contact:

Email: xiew@mcmaster.ca
Wenli Xie, MSc, CCRC
Phone: 905-521-2100 ext. 73864


Location Contact:

Philadelphia, Pennsylvania 19104
United States

Jessica Britton
Phone: 267-426-7633
Email: brittonj@email.chop.edu

Site Status: Recruiting


Data Source: ClinicalTrials.gov

Date Processed: November 18, 2019

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