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

NCT ID: NCT06662253

Last Updated: 2024-10-28

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 150 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-01-31
• Study Completion Date: 2026-09-30

Brief Summary

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.

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.

Conditions

Venous Thromboembolism (VTE); Trauma Related Injuries

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Study Groups

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.

Group Type: ACTIVE_COMPARATOR

Standard of Care Dosing

Intervention Type: DRUG

Participants will receive Enoxaparin dosed at the discretion of the most responsible physician (MRP). In cases of severe renal insufficiency (CrCl \&lt; 30mL/min\^:), the LMWH may dose reduced or changed to Heparin at the discretion of the MRP.

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.

Group Type: EXPERIMENTAL

Anti-Xa Guided Dosing of Low Molecular Weight Heparin

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: 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 \&lt; 30mL/min\^:), the LMWH may dose reduced or changed to Heparin at the discretion of the MRP.

Intervention Type: DRUG

Eligibility Criteria

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 &lt; 30.

6. Expected discharge or transfer from hospital within 72 hours.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Alexandre Tran

OTHER

Sponsor Role: lead

Responsible Party

Alexandre Tran

Associate Scientist

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Alexandre Tran, MD, MSc, FRCSC

Role: PRINCIPAL_INVESTIGATOR

Ottawa Hospital Research Institute

Marc Carrier, MD, MSc, FRCPC

Role: PRINCIPAL_INVESTIGATOR

Ottawa Hospital Research Institute

Central Contacts

Alexandre Tran, MD, MSc, FRCSC

Role: CONTACT

aletran@toh.ca

613-737-8899 ext. 17076

Rebecca Porteous, RN, BNSC, CCRP

Role: CONTACT

rporteous@ohri.ca

613-737-8899 ext. 17076

Other Identifiers

20240579-01H

Identifier Type: -

Identifier Source: org_study_id