PREVENTion of Clot in Orthopaedic Trauma (PREVENT CLOT)

PREVENTion of Clot in Orthopaedic Trauma (PREVENT CLOT): A Randomized Pragmatic Trial Comparing the Complications and Safety of Blood Clot Prevention Medicines Used in Orthopaedic Trauma Patients

The purpose of this study is to compare aspirin versus low-molecular weight heparin (LMWH) (Enoxaparin) as a thromboprophylaxis in patients who sustain a fracture.

Study Overview

• Status: Completed
• Conditions: Trauma; Blood Clot
• Intervention / Treatment: Drug: Low Molecular Weight Heparin (LMWH); Drug: Acetylsalicylic acid

Detailed Description

Patients who sustain orthopaedic trauma are at an increased risk of venous thromboembolism (VTE), including fatal pulmonary embolism (PE). Current guidelines recommend low-molecular-weight heparin (LMWH) for VTE prophylaxis in orthopaedic trauma patients. However, emerging literature in total joint arthroplasty patients suggests the potential clinical benefits of VTE prophylaxis with aspirin. This trial aims to determine if aspirin is non-inferior to LMWH for thromboprophylaxis in fracture patients.

• Study Type: Interventional
• Enrollment (Actual): 12424
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Calgary, Alberta, Canada
      • University of Calgary, Foothills Medical Centre
  • Ontario
    • Hamilton, Ontario, Canada
      • McMaster University, Hamilton General Hospital
• United States
  • Arizona
    • Tucson, Arizona, United States, 85724
      • University of Arizona
  • Florida
    • Miami, Florida, United States, 33136
      • University of Miami Ryder Trauma Center
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Methodist Hospital
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • University of Maryland R Adams Cowley Shock Trauma Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
  • Mississippi
    • Jackson, Mississippi, United States, 39216
      • University of Mississippi Medical Center
  • New Hampshire
    • Lebanon, New Hampshire, United States, 03756
      • Dartmouth-Hitchcock Medical Center
  • North Carolina
    • Charlotte, North Carolina, United States, 28204
      • Carolinas Medical Center
    • Winston-Salem, North Carolina, United States, 27157
      • Wake Forest University Baptist Medical Center
  • Ohio
    • Cleveland, Ohio, United States, 44109
      • MetroHealth Medical Center
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15212
      • Allegheny General Hospital
  • Rhode Island
    • Providence, Rhode Island, United States, 02903
      • Rhode Island Hospital, Brown University
  • Tennessee
    • Memphis, Tennessee, United States, 38103
      • University of Tennessee, RegionOne Medical Center
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt Medical Center
  • Texas
    • Houston, Texas, United States, 77030
      • University of Texas Health Science Center at Houston
    • San Antonio, Texas, United States, 78219
      • San Antonio Military Medical Center
  • Virginia
    • Falls Church, Virginia, United States, 22042
      • Inova Fairfax Hospital
  • Washington
    • Seattle, Washington, United States, 98104
      • Harborview Medical Center
  • Wisconsin
    • Madison, Wisconsin, United States, 53705
      • University of Wisconsin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patients who have a planned operative or non-operative pelvis or acetabular fracture, or any operative extremity fracture proximal to the metatarsals or carpals.
• Patients at increased risk of blood clot(s) from their orthopaedic injury(ies) and will receive prophylactic blood thinner regimen per standard of care.
• Patients 18 years or older.

Exclusion Criteria:

• Patients who present to the hospital more than 48 hours post injury
• Patients who received more than 2 doses of LMWH or aspirin for initial VTE prophylaxis
• Patients on long term blood thinners (other than low-dose aspirin or platelet inhibitors such as Plavix or Aggrenox)
• Patients who have had a VTE within the last 6 months
• Patients on therapeutic (as opposed to prophylactic) blood thinners for an acute issue at the time of admission
• Patients who have a newly diagnosed indication for therapeutic blood thinners (for example vascular injury) that will require therapeutic anticoagulation for more than one week
• Patients who cannot receive either of the study medications due to an allergy (history of heparin induced thrombocytopenia, allergy to aspirin, or NSAIDs) or other medical contraindication to blood thinners
• Patients who are on higher dose aspirin (>81 mg once a day or higher) for medical reasons or who will be treated with higher dose aspirin
• Patients with underlying chronic clotting disorders (i.e. Factor V Leiden, hyperhomocysteinemia, Protein C and S deficiency) that require full dose anticoagulation or are a contraindication to venous thromboembolism chemoprophylaxis
• Patients with end stage renal disease or impaired creatinine clearance <30 ml/min at time of randomization(note: creatinine clearance does not need to be documented if prescribing physician would order medication without test as SOC)
• Pregnant or lactating patients
• Prisoners
• Patients who do not speak either English or Spanish
• Patients who are likely to have severe problems maintaining follow-up
• Patients, based upon the clinical judgment of the treating clinician, NOT equally suited for treatment with either aspirin or low-molecular-weight heparin
• Patients may be excluded for other reasons at the discretion of the treating physician; the reason for exclusion must be documented on the screening form
• Patients who have a known COVID-19 diagnosis prior to fracture treatment or within 3 months of the index fracture

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Low Molecular Weight Heparin (LMWH)-Enoxaparin; Injection of 30 mg enoxaparin, twice a day via injection	Drug: Low Molecular Weight Heparin (LMWH); The LMWH intervention will be 30 mg enoxaparin subcutaneous (under the skin) twice a day with variations in dosing allowed, per the standard of care at sites, as needed for patients who are very obese or exhibit renal dysfunction.; Other Names: Enoxaparin
Active Comparator: Acetylsalicylic acid (ASA)-Aspirin; Enteral ingestion or administration of 81 mg ASA, twice a day	Drug: Acetylsalicylic acid; The Aspirin intervention will be 81 mg enteral (by mouth, feeding tube or rectal) twice a day with no variation in dosing allowed.; Other Names: Aspirin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With All-cause Mortality	Death from any cause	90 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Cause-specific Death	Cause specific death. Some participants are reported twice if reason for death met more than one category.	90 days
Non-fatal Pulmonary Embolism		90 days
Deep Vein Thrombosis		90 days
Bleeding Complication		90 days
Wound Complication		90 days
Deep Surgical Site Infection		90 days

Collaborators and Investigators

• Sponsor: Major Extremity Trauma Research Consortium
• Collaborators: Patient-Centered Outcomes Research Institute
• Investigators: Principal Investigator: Robert O'Toole, MD, University of Maryland; Study Director: Tara Taylor, MPH, Johns Hopkins Bloomberg School of Public Health; Study Director: Katherine Frey, PhD, MPH, RN, Johns Hopkins Bloomberg School of Public Health; Principal Investigator: Renan Castillo, PhD, Johns Hopkins Bloomberg School of Public Health

Publications and helpful links

General Publications

• O'Toole RV, Stein DM, Frey KP, O'Hara NN, Scharfstein DO, Slobogean GP, Taylor TJ, Haac BE, Carlini AR, Manson TT, Sudini K, Mullins CD, Wegener ST, Firoozabadi R, Haut ER, Bosse MJ, Seymour RB, Holden MB, Gitajn IL, Goldhaber SZ, Eastman AL, Jurkovich GJ, Vallier HA, Gary JL, Kleweno CP, Cuschieri J, Marvel D, Castillo RC; METRC. PREVENTion of CLots in Orthopaedic Trauma (PREVENT CLOT): a randomised pragmatic trial protocol comparing aspirin versus low-molecular-weight heparin for blood clot prevention in orthopaedic trauma patients. BMJ Open. 2021 Mar 24;11(3):e041845. doi: 10.1136/bmjopen-2020-041845.
• O'Hara NN, Degani Y, Marvel D, Wells D, Mullins CD, Wegener S, Frey K, Joseph T, Hurst J, Castillo R, O'Toole RV; PREVENT CLOT Stakeholder Committee. Which orthopaedic trauma patients are likely to refuse to participate in a clinical trial? A latent class analysis. BMJ Open. 2019 Oct 11;9(10):e032631. doi: 10.1136/bmjopen-2019-032631.

Study record dates

Study Major Dates

• Study Start (Actual): April 24, 2017
• Primary Completion (Actual): February 18, 2022
• Study Completion (Actual): February 18, 2022

Study Registration Dates

• First Submitted: December 2, 2016
• First Submitted That Met QC Criteria: December 5, 2016
• First Posted (Estimated): December 6, 2016

Study Record Updates

• Last Update Posted (Actual): May 14, 2024
• Last Update Submitted That Met QC Criteria: April 17, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: Deep Vein Thrombosis; Venous Thromboembolism; Trauma; Thromboprophylaxis; Pulmonary Embolism; Blood clot; Blood clot prevention; trauma patients
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Embolism and Thrombosis; Wounds and Injuries; Thrombosis; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Fibrinolytic Agents; Fibrin Modulating Agents; Platelet Aggregation Inhibitors; Cyclooxygenase Inhibitors; Antipyretics; Anticoagulants; Aspirin; Heparin; Enoxaparin; Heparin, Low-Molecular-Weight; Tinzaparin; Dalteparin
• Other Study ID Numbers: PCS-1511-32745

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No