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

Alexandre Tran

Status and phase: Not yet enrolling; Phase 3; Phase 2

Conditions: Trauma Related Injuries; Venous Thromboembolism (VTE)

Treatments: Drug: Anti-Xa Guided Dosing of Low Molecular Weight Heparin; Drug: Standard of Care Dosing

Study type: Interventional

Funder types: Other

Identifiers

NCT06662253

20240579-01H

Details and patient eligibility

About

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.

Full 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.

Enrollment: 150 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)

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150 participants in 2 patient groups

Standard of Care

Active Comparator group

Description:

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.

Treatment:

Drug: Standard of Care Dosing

Intervention (Anti-Xa Guided)

Experimental group

Description:

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.

Treatment:

Drug: Anti-Xa Guided Dosing of Low Molecular Weight Heparin