A Different Approach to Preventing Thrombosis

Pulmonary Embolism Clinical Trial

— ADAPT  

Official title:

A Different Approach to Preventing Thrombosis (ADAPT): A Randomized Controlled Trial Comparing Low Molecular Weight Heparin to Acetylsalicylic Acid in Orthopedic Trauma Patients

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02774265
• Other study ID #: HP-00065750
• Status: Completed
• Phase: Phase 3
• Start date: January 2016
• Est. completion date: September 2017

Study information

• Verified date: January 2022
• Source: University of Maryland, Baltimore
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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:

1. To compare the bleeding complication outcomes associated with LMWH versus ASA in patients receiving VTE prophylaxis following high-risk lower extremity fractures.

2. 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.

3. To compare the 6-month treatment costs associated with VTE prophylaxis using either LMWH or ASA for high-risk lower extremity fracture patients

Hypothesis:

1. 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.

2. 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.

3. 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:

1. 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

2. 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.

3. 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:

1. VTE prophylaxis with Enoxaparin 30mg SC BID

2. VTE prophylaxis with ASA 81mg PO BID

Recruitment information / eligibility

• Status: Completed
• Enrollment: 329
• Est. completion date: September 2017
• Est. primary completion date: May 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Embolism
• Pulmonary Embolism
• Thromboembolism
• Thrombosis
• Venous Thromboembolism

Intervention

Drug:
• VTE prophylaxis with Enoxaparin 30mg BID
Patients will receive Enoxaparin 30mg BID for DVT prophylaxis and will be followed to determine the efficacy, safety and cost when used for VTE prophylaxis in high-risk orthopedic traumas administered for the length of time indicated by standard of care based on the injury.
• VTE prophylaxis with Aspirin 81mg BID
Patients will receive Aspirin 81mg BID for DVT prophylaxis and will be followed to determine the efficacy, safety and cost when used for VTE prophylaxis in high-risk orthopedic traumas administered for the length of time indicated by standard of care based on the injury.

Locations

Country	Name	City	State
United States	University of Maryland Medical Center	Baltimore	Maryland

Sponsors (1)

Lead Sponsor	Collaborator
University of Maryland, Baltimore

Country where clinical trial is conducted

United States, 

References & Publications (40)

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* Note: There are 40 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants With Treatment-related Bleeding Events as Assessed by the Need for Blood Transfusions and Procedures for Bleeding Complications After Initiation of the Study Medication.	Includes a greater than 2g/dL drop in hemoglobin, blood transfusion, hematoma evacuation, re-operation for a deep surgical site infection or minor procedure for bleeding and GI bleed	90 days
Secondary	Number of Participants With Deep Venous Thromboembolism	DVT and how the diagnosis was made will be recorded. The number of events in participants in each arm will be compared to evaluate efficacy.	90 days
Secondary	Number of Participants With Pulmonary Embolism Events	Bases on imaging obtained for symptoms.	90 days