PREVENTion of Clot in Orthopaedic Trauma

NCT02984384 | Completed Phase 3 Results DMC FDA Drug

• 1 other identifier: PCS-1511-32745
• Study Type: interventional
• Target: 12,424
• Locations: 2 countries
• Sites: 21

Brief Summary

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.

Conditions

Blood Clot; Trauma

Keywords

Trauma; Blood clot; Venous Thromboembolism; Pulmonary Embolism; Deep Vein Thrombosis; Thromboprophylaxis; Blood clot prevention; trauma patients

Outcome Measures

Primary Outcomes (1)

• Number of Participants With All-cause Mortality

  Death from any cause

  90 days

Secondary Outcomes (6)

• Number of Participants With Cause-specific Death

  90 days

• Non-fatal Pulmonary Embolism

  90 days

• Deep Vein Thrombosis

  90 days

• Bleeding Complication

  90 days

• Wound Complication

  90 days

Study Arms (2)

Low Molecular Weight Heparin (LMWH)-Enoxaparin

ACTIVE COMPARATOR

Injection of 30 mg enoxaparin, twice a day via injection

Drug: Low Molecular Weight Heparin (LMWH)

Acetylsalicylic acid (ASA)-Aspirin

ACTIVE COMPARATOR

Enteral ingestion or administration of 81 mg ASA, twice a day

Drug: Acetylsalicylic acid

Interventions

Acetylsalicylic acid DRUG

The Aspirin intervention will be 81 mg enteral (by mouth, feeding tube or rectal) twice a day with no variation in dosing allowed.

Also known as: Aspirin

Acetylsalicylic acid (ASA)-Aspirin

Low Molecular Weight Heparin (LMWH) DRUG

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.

Also known as: Enoxaparin

Low Molecular Weight Heparin (LMWH)-Enoxaparin

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Major Extremity Trauma Research Consortium: lead
• Patient-Centered Outcomes Research Institute: collaborator

Study Sites (21)

University of Arizona

Tucson, Arizona, 85724, United States

Location

University of Miami Ryder Trauma Center

Miami, Florida, 33136, United States

Location

Methodist Hospital

Indianapolis, Indiana, 46202, United States

Location

University of Maryland R Adams Cowley Shock Trauma Center

Baltimore, Maryland, 21201, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

University of Mississippi Medical Center

Jackson, Mississippi, 39216, United States

Location

Dartmouth-Hitchcock Medical Center

Lebanon, New Hampshire, 03756, United States

Location

Carolinas Medical Center

Charlotte, North Carolina, 28204, United States

Location

Wake Forest University Baptist Medical Center

Winston-Salem, North Carolina, 27157, United States

Location

MetroHealth Medical Center

Cleveland, Ohio, 44109, United States

Location

Allegheny General Hospital

Pittsburgh, Pennsylvania, 15212, United States

Location

Rhode Island Hospital, Brown University

Providence, Rhode Island, 02903, United States

Location

University of Tennessee, RegionOne Medical Center

Memphis, Tennessee, 38103, United States

Location

Vanderbilt Medical Center

Nashville, Tennessee, 37232, United States

Location

University of Texas Health Science Center at Houston

Houston, Texas, 77030, United States

Location

San Antonio Military Medical Center

San Antonio, Texas, 78219, United States

Location

Inova Fairfax Hospital

Falls Church, Virginia, 22042, United States

Location

Harborview Medical Center

Seattle, Washington, 98104, United States

Location

University of Wisconsin

Madison, Wisconsin, 53705, United States

Location

University of Calgary, Foothills Medical Centre

Calgary, Alberta, Canada

Location

McMaster University, Hamilton General Hospital

Hamilton, Ontario, Canada

Location

Related Publications (3)

• 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.

  PMID: 33762229 BACKGROUND

• Major Extremity Trauma Research Consortium (METRC); O'Toole RV, Stein DM, O'Hara NN, Frey KP, Taylor TJ, Scharfstein DO, Carlini AR, Sudini K, Degani Y, Slobogean GP, Haut ER, Obremskey W, Firoozabadi R, Bosse MJ, Goldhaber SZ, Marvel D, Castillo RC. Aspirin or Low-Molecular-Weight Heparin for Thromboprophylaxis after a Fracture. N Engl J Med. 2023 Jan 19;388(3):203-213. doi: 10.1056/NEJMoa2205973.

  PMID: 36652352 DERIVED

• 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.

  PMID: 31604788 DERIVED

MeSH Terms

Conditions

Thrombosis; Wounds and Injuries; Venous Thromboembolism; Pulmonary Embolism; Venous Thrombosis

Interventions

Aspirin; Heparin, Low-Molecular-Weight; Enoxaparin

Condition Hierarchy (Ancestors)

Embolism and Thrombosis; Vascular Diseases; Cardiovascular Diseases; Thromboembolism; Lung Diseases; Respiratory Tract Diseases; Embolism

Intervention Hierarchy (Ancestors)

Salicylates; Hydroxybenzoates; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Heparin; Glycosaminoglycans; Polysaccharides; Carbohydrates

Results Point of Contact

• Title: Robert O'Toole
• Organization: University of Maryland School of Medicine

rotoole@som.umaryland.edu

410-328-6280

Study Officials

• Robert O'Toole, MD

  University of Maryland

  PRINCIPAL INVESTIGATOR

• Renan Castillo, PhD

  Johns Hopkins Bloomberg School of Public Health

  PRINCIPAL INVESTIGATOR

• Tara Taylor, MPH

  Johns Hopkins Bloomberg School of Public Health

  STUDY DIRECTOR

• Katherine Frey, PhD, MPH, RN

  Johns Hopkins Bloomberg School of Public Health

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 2, 2016
• First Posted: December 6, 2016
• Study Start: April 24, 2017
• Primary Completion: February 18, 2022
• Study Completion: February 18, 2022
• Last Updated: May 14, 2024
• Results First Posted: May 14, 2024

Record last verified: 2024-04

Locations

US (19); CA (2)