Anti-Xa Guided Dosing of Low Molecular Weight Heparin for Prevention of Venous Thromboembolism Following Traumatic Injury: a Multicentre Pilot Randomized Trial (PrOVE iT)

This multicentre pilot trial will assess the feasibility of a full-scale, randomized trial to determine whether bloodwork guided dosing of blood thinners reduces the risk of clotting in high-risk trauma patients. Patients will receive either standard of care dosing or dosing with adjustments based on bloodwork to achieve a minimum therapeutic threshold.

Study Overview

• Status: Not yet recruiting
• Conditions: Venous Thromboembolism (VTE); Trauma Related Injuries
• Intervention / Treatment: Drug: Standard of Care Dosing; Drug: Anti-Xa Guided Dosing of Low Molecular Weight Heparin

Detailed Description

This multicentre pilot trial will assess the feasibility of a full-scale, randomized trial to determine whether anti-Xa guided dosing of low molecular heparin (LMWH) reduces the risk of venous thromboembolism (VTE) in high-risk trauma patients. Patients will receive either standard of care fixed dosing of Enoxaparin or 0.5 mg/kg twice daily with dose adjustments to achieve an anti-Xa trough level between 0.1 and 0.2 IU/mL.

• Study Type: Interventional
• Enrollment (Estimated): 150
• Phase: Phase 2; Phase 3

Contacts and Locations

• Study Contact: Name: Alexandre Tran, MD, MSc, FRCSC; Phone Number: 17076 613-737-8899; Email: aletran@toh.ca
• Study Contact Backup: Name: Rebecca Porteous, RN, BNSC, CCRP; Phone Number: 17076 613-737-8899; Email: rporteous@ohri.ca

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patients 18 years of age or older admitted to a hospital ward or intensive care unit following a traumatic injury involving two or more body systems (head, chest, abdomen, pelvis, extremity) and meeting at least one of the following high-risk criteria previously identified in a recent systematic review (1): age ≥ 65, body mass index ≥ 30 kg/m2, injury severity score ≥ 16, pelvic injury with activity restrictions, lower extremity injury with activity restrictions, or surgery during the index hospitalization.

To be eligible, patients must be deemed appropriate for pharmacologic prophylaxis by the most responsible physician and randomized with the intention to receive prophylaxis within 48 hours of admission. Prior to randomization, there is no restriction on whether or not patients have previously received pharmacologic or mechanical prophylaxis.

Exclusion Criteria:

1. Greater than 7 days since time of injury.
2. Requirement for therapeutic anticoagulation or dual-antiplatelet therapy
3. Unable or unwilling to receive pharmacologic prophylaxis within 48 hours of admission.
4. History of allergic reaction or sensitivity to LMWH.
5. Thrombocytopenia with platelets < 30.
6. Expected discharge or transfer from hospital within 72 hours.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Standard of Care; Participants will receive Enoxaparin dosed at the discretion of the most responsible physician (MRP). In cases of severe renal insufficiency (CrCl < 30mL/min^:), the LMWH may dose reduced or changed to Heparin at the discretion of the MRP.	Drug: Standard of Care Dosing; Participants will receive Enoxaparin dosed at the discretion of the most responsible physician (MRP). In cases of severe renal insufficiency (CrCl < 30mL/min^:), the LMWH may dose reduced or changed to Heparin at the discretion of the MRP.
Experimental: Intervention (Anti-Xa Guided); Participants will receive Enoxaparin 0.5 mg/kg twice daily (rounded up or down to the nearest 10 mg) the initial starting dose. Dose adjustments will be made based on trough levels drawn between the 3rd and 4th dose. The target anti-Xa level range is between 0.1 and 0.2 IU/mL. If the patient is below the target range, then the next Enoxaparin dose will be increased by 10 mg per dose with a new trough anti-Xa level 24 hours after dose modification. If the patient is above the target range, then the next Enoxaparin dose will be decreased by 10 mg per dose with a new trough anti-Xa level 24 hours after dose modification. This dose will be maintained until hospital discharge.	Drug: Anti-Xa Guided Dosing of Low Molecular Weight Heparin; Participants will receive Enoxaparin 0.5 mg/kg twice daily (rounded up or down to the nearest 10 mg) the initial starting dose. Dose adjustments will be made based on trough levels drawn between the 3rd and 4th dose. The target anti-Xa level range is between 0.1 and 0.2 IU/mL. If the patient is below the target range, then the next Enoxaparin dose will be increased by 10 mg per dose with a new trough anti-Xa level 24 hours after dose modification. If the patient is above the target range, then the next Enoxaparin dose will be decreased by 10 mg per dose with a new trough anti-Xa level 24 hours after dose modification. This dose will be maintained until hospital discharge.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Recruitment (Patients per site per month)	The pilot trial will have an expected duration of 15 months during which time we hope to enroll at least 150 participants total across all sites - therefore, 5 patients/site/month. There are no maximum enrollment targets for each site.	Participants per site per month x 15 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Eligibility rate	Proportion of screened patients who are eligible	15 months
Consent rate	Proportion of eligible patients who provide consent	15 months
Retention rate	Proportion of participants retained at follow-up	15 months
Study completion rate	Proportion of participants who completed all study procedures	15 months
Adherence rate	Adherence to study drug measured by proportion of prophylaxis doses received.	15 months
Adherence to monitoring	Proportion of patients with anti-Xa tests ordered appropriately	15 months
Adherence to dose adjustment	Proportion of doses adjusted appropriately for anti-Xa level	15 months
Adherence to anti-Xa target	Proportion of patients who achieved target anti-Xa range	15 months
Reasons for declining participation	Reasons for declining participation	15 months

Collaborators and Investigators

• Sponsor: Alexandre Tran
• Investigators: Principal Investigator: Alexandre Tran, MD, MSc, FRCSC, Ottawa Hospital Research Institute; Principal Investigator: Marc Carrier, MD, MSc, FRCPC, Ottawa Hospital Research Institute

Study record dates

Study Major Dates

• Study Start (Estimated): January 1, 2025
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): September 1, 2026

Study Registration Dates

• First Submitted: October 24, 2024
• First Submitted That Met QC Criteria: October 24, 2024
• First Posted (Actual): October 28, 2024

Study Record Updates

• Last Update Posted (Actual): October 28, 2024
• Last Update Submitted That Met QC Criteria: October 24, 2024
• Last Verified: September 1, 2024

More Information

Terms related to this study

• Keywords: trauma; prophylaxis; venous thromboembolism
• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Embolism and Thrombosis; Wounds and Injuries; Thromboembolism; Venous Thromboembolism; Molecular Mechanisms of Pharmacological Action; Fibrin Modulating Agents; Fibrinolytic Agents; Anticoagulants; Tinzaparin; Heparin; Heparin, Low-Molecular-Weight; Dalteparin
• Other Study ID Numbers: 20240579-01H

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No