A Different Approach to Preventing Thrombosis (ADAPT)

University of Maryland Baltimore (UMB)

Status and phase

Completed

Phase 3

Conditions

Pulmonary Embolism

Venous Thromboembolism

Treatments

Drug: VTE prophylaxis with Aspirin 81mg BID

Drug: VTE prophylaxis with Enoxaparin 30mg BID

Study type

Interventional

Funder types

Other

Identifiers

NCT02774265

HP-00065750

Details and patient eligibility

About

The purpose of this study is to perform a pragmatic randomized controlled trial to compare the use of low molecular weight heparin (LMWH, lovenox, enoxaparin) versus acetylsalicylic acid (ASA) for venous thromboembolism (VTE) prophylaxis in patients with high-risk lower extremity fractures.

Full description

Purpose:

To perform a pragmatic randomized controlled trial of the use of low molecular weight heparin (LMWH, enoxaparin, lovenox) versus Aspirin (ASA) for VTE prophylaxis in patients with high-risk extremity fractures.

Specific Aims:

To compare the bleeding complication outcomes associated with LMWH versus ASA in patients receiving VTE prophylaxis following high-risk lower extremity fractures.
To compare the incidence of clinically important VTE events associated with LMWH versus ASA for VTE prophylaxis in patients receiving VTE prophylaxis following high-risk lower extremity fractures.
To compare the 6-month treatment costs associated with VTE prophylaxis using either LMWH or ASA for high-risk lower extremity fracture patients

Hypothesis:

Among patients with high risk lower extremity fractures receiving VTE prophylaxis, the rate of bleeding complications will be lower for patients receiving ASA compared to those receiving LMWH.
Among patients with high risk lower extremity fractures receiving VTE prophylaxis, the rate of VTE for patients receiving ASA will be no greater than those receiving LMWH.
Among patients with high risk lower extremity fractures receiving VTE prophylaxis, the 6-month treatment costs will be lower for patients receiving ASA compared to those receiving LMWH.

Methods/Outcomes:

A randomized controlled trial will be conducted to assess the use of LMWH versus ASA for VTE prophylaxis in patients with high-risk extremity fractures.

The aim-specific outcomes to be collected are as follows:

A composite of the following major bleeding related complications:
1. Fatal bleeding into a critical organ (retroperitoneal, intracranial, intraocular, intraspinal)
2. Clinically overt bleed with a > 2g/dL drop in Hb or requiring > 2U transfusion
3. Wound drainage or hematoma requiring reoperation
4. Diagnosis of deep surgical site infection
VTE Events defined as a composite of any symptomatic proximal DVT (in the femoral or popliteal vessels), or PE (central, segmental or subsegmental). All VTE events will be confirmed using multiplanar CT scan or formal venous duplex exam.
Cost of VTE prophylaxis treatment, VTE events and bleeding related complications.

Data Collection:

Patients meeting inclusion/exclusion criteria will be prospectively randomized to one of two treatment arms. Block randomization will be used. Patients will receive VTE prophylaxis as allocated, and followed for their index hospitalization and a 3month period post discharge for VTE events and bleeding complications. Outcome data will be prospectively collected during index hospitalization, and at 2 weeks and 3 months post discharge, and blind analysis and interpretation of results will be performed at 50% and 100% recruitment.

Data Analysis:

All data will be reported as mean and standard deviations for continuous variables and proportions and percentages for categorical data. Kaplan-Meier survival and Cox proportional hazard analysis will be completed for time to VTE and bleeding complication outcomes. Sub-group analysis will include Injury Severity Score and fracture location. An independent Data Safety and Monitoring Committee will complete interim analysis at 50% recruitment. A cost analysis will be conducted using a 6month and lifetime time horizon with a societal perspective. Component costs will consist of: VTE prophylaxis costs, unscheduled follow-ups, emergency room visit, hospital admission or unscheduled repeat surgical intervention for VTE or bleeding complications.

Study Treatment Arms:

VTE prophylaxis with Enoxaparin 30mg SC BID
VTE prophylaxis with ASA 81mg PO BID

Enrollment

329 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion criteria

All patients treated at a level-1 trauma center with any one or more of the following injuries: Pelvis fracture (operative or non-operative), Acetabulum fracture (operative or non-operative), or any operative extremity fracture (proximal to metatarsals/carpals)
Age greater than or equal to 18 years old

Exclusion criteria

Patients receiving pre-existing confounding prophylaxis or therapeutic anticoagulation (not to include anti-platelet agents) prior to admission or those receiving greater than one dose of LMWH since injury
Patients with pre-existing coagulopathy
Patients with a previous history of VTE within the last 6 months
Patients who are pregnant
Patients with CNS or spinal cord injury with potential need for further neurosurgical intervention precluding anticoagulation with aspirin
Patients with active bleeding precluding the use of anticoagulation
Impaired creatinine clearance <30ml/min at the time of randomization
History of Heparin Induced Thrombocytopenia or ASA or NSAID allergy
Prisoners
Non-english speaking patients
Patients who have an indication for therapeutic anticoagulation
Patients deemed inappropriate for inclusion in the study by their treating physician. Reason must be documented
Patients who would not normally receive VTE prophylaxis for their injury