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


Study is Available At:


Original ID:

HamiltonHSC


NCT ID:

NCT02486666


Secondary ID:


Study Acronym:

FiXET


Brief Title:

Pilot Feasibility and Safety of Administering Weight Adjusted Fixed LMWH Dose


Official Title:

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


Overall Status:

Recruiting


Study Phase:

Phase 3


Genders:

N/A


Minimum Age:

N/A


Maximum Age:

60 Days


Quick Facts

Healthy Volunteers
Oversight Has DMC
Study Is FDA Regulated
Study Is Section 801
Has Expanded Access

Study Source:

Hamilton Health Sciences Corporation


Oversight Authority:

Canada: Health Canada


Reasons Why Stopped:


Study Type:

Interventional


Study Design:


Number of Arms:

2


Number of Groups:

0


Total Enrollment:

20


Enrollment Type:

Anticipated


Overall Contact Information

Official Name:Mihir Bhatt, MD
Principal Investigator
HHSC/McMaster Children's Hospital
Primary Contact:Korinne Hamilton, MSc, CCRA
905-521-2100 ext. 76054
905-521-2100
hamiltonko@hhsc.ca
Backup Contact:Wenli Xie, MSc, CCRC
905-521-2100 ext. 73864
905-521-2100
xiew@mcmaster.ca

Study Dates

Start Date:March 2016
Completion Date:December 2020
Completion Type:Anticipated
Primary Completion Date:December 2019
Primary Completion Type:Anticipated
Verification Date:October 2019
Last Changed Date:October 11, 2019
First Received Date:May 14, 2015

Study Outcomes

Outcome Type:Secondary Outcome
Measure:Safety of anticoagulation
Time Frame:6-12 months
Safety Issues:False
Description:Mean anti-Xa levels Number of Enoxaparin dose adjustments in the control arm Number of venipuncture attempts for blood sampling These Categorical variables will be combined to analyse the safety of this FiXET dose anticoagulation therapy on patients
Outcome Type:Secondary Outcome
Measure:Efficacy in resolution of thrombosis
Time Frame:6-12 months
Safety Issues:False
Description:-Rate of thrombosis resolution
Outcome Type:Primary Outcome
Measure:Safety of administering a weight adjusted fixed dose of enoxaparin to neonates with thrombosis
Time Frame:6-12 months
Safety Issues:False
Description:- Percentage of subjects removed from the study due to 1) low or high anti Xa levels or 2) major bleeding
Outcome Type:Primary Outcome
Measure:Feasibility of recruiting at least 5 subjects over the study period per center
Time Frame:6-12 months
Safety Issues:False
Description: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

Study Interventions

Intervention Type:Drug
Name:Enoxaparin
Description:WEIGHT ADJUSTED FiXED DOSE OF LOW MOLECULAR WEIGHT HEPARIN (ENOXAPARIN) TO NEONATES WITH THROMBOSIS (FiXET)
Arm Name:Experimental Arm
Other Name:Enoxaparin sodium

Study Arms

Study Arm Type:Other
Arm Name:Control Arm
Description: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). 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.
Study Arm Type:Experimental
Arm Name:Experimental Arm
Description: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.

Study Agencies

Agency Class:Other
Agency Type:Lead Sponsor
Agency Name:Hamilton Health Sciences Corporation
Agency Class:Other
Agency Type:Collaborator
Agency Name:IWK Health Centre

Sample and Retention Information

There are no available Sample and Retention Information

Study References

There are no available Study References

Data Source: ClinicalTrials.gov

Date Processed: January 21, 2020

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