Transfusion Trigger After Operations in High Cardiac Risk Patients

NCT03229941 | Completed Results DMC

• 1 other identifier: 599
• Study Type: interventional
• Target: 1,424
• Locations: 1 country
• Sites: 16

Brief Summary

The goal of the proposed study is to determine whether a liberal transfusion strategy (transfusion trigger at Hb \< 10 gm/dl) in Veterans at high cardiac risk who undergo major open vascular and general surgery operations is associated with decreased risk of adverse postoperative outcomes compared to a restrictive transfusion strategy (transfusion trigger at Hb \< 7 gm/dl).

Conditions

Myocardial Infarction; Coronary Revascularization; Acute Renal Failure

Outcome Measures

Primary Outcomes (1)

• A Composite Endpoint of All-cause Post-randomization Mortality, Myocardial Infarction (MI), Coronary Revascularization, Acute Renal Failure, or Post-randomization Ischemic Stroke up to 90 Days After Randomization

  MI will be defined using the Third Universal Definition of Myocardial Infarction. Acute renal failure will be defined as Acute Kidney Injury stage III according to RIFLE criteria. Baseline creatinine will be considered the creatinine upon admission prior to the index operation. The above urine output criteria will be only used for patients who are in the ICU and have precise monitoring of their urinary output. For patients on the surgical floor only serum creatinine changes will be used for assessment of this endpoint. Coronary revascularization will be defined as a coronary artery bypass graft, or percutaneous coronary intervention (either angioplasty or stenting). Stroke will be defined as new unilateral neurological deficit that lasts for more than 24 hours, and is confirmed by a brain imaging modality (computed tomography or magnetic resonance imaging study) demonstrating new brain infarct.

  90 days after randomization

Secondary Outcomes (5)

• A Composite Endpoint of Postoperative Infectious Complications at 90 Days Post-randomization: Infectious Complications Will Include Wound Infections, Pneumonia, and Sepsis

  90 days after randomization

• A Composite Endpoint of Cardiac Complications (Other Than MI) at 90 Days Post-randomization: Cardiac Complications Include New Cardiac Arrhythmias That Necessitate New Treatment, New or Worsening Congestive Heart Failure, and Non Fatal Cardiac Arrest

  90 days after randomization

• All-cause Mortality at 1 Year After Randomization

  12 months after randomization

• A Composite Endpoint of All-cause Mortality, MI, Coronary Revascularization, Acute Renal Failure, or Postoperative Ischemic Stroke

  30 days after randomization

• Length of Hospital Stay

  At hospital discharge, up to 1 year

Study Arms (2)

Restrictive

EXPERIMENTAL

Transfusion trigger: Hb\<7gm/dl

Procedure: Blood Transfusion

Liberal

EXPERIMENTAL

Transfusion trigger: Hb\<10gm/dl

Procedure: Blood Transfusion

Interventions

Blood Transfusion PROCEDURE

Blood Transfusion

Liberal; Restrictive

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Males and females older than 18 years of age who have postoperative Hb \< 10gm/dl within 15 days after the index operation
• Patients who undergo an operation in either one of the three following categories:
• Veterans who undergo PAD - related operations including but not limited to the following:
• aortobifemoral or aortobiiliac bypass
• open abdominal aortic aneurysm repair with simultaneous repair of aortoiliac occlusive disease
• visceral bypass
• iliofemoral bypass
• femoral bypass or endarterectomy
• infrainguinal bypass
• thromboembolectomy
• supra-aortic trunk bypass or endarterectomy
• carotid endarterectomy
• major lower extremity amputations (transfemoral, through the knee, or transtibial)
• Veterans with past medical history of ischemic stroke or IHD or PAD who undergo the following general surgery procedures, defined as:
• known prior MI

You may not qualify if:

• Veteran unable to consent
• Veteran unwilling to follow protocol (such as Jehovah's witnesses)
• Veteran with known history of hereditary anemias such as Thalassemia or Sickle cell disease
• Veteran with known history of hereditary bleeding disorders, such as factor VIII or factor IX deficiency
• Veteran with prior history of adverse reaction to blood administration, such as fever, rash, or hemolysis
• Veteran does not speak or understand English
• Veteran hemodynamically unstable or in cardiogenic shock for \>48 hours after the index procedure
• Veteran participating in another interventional trial whose objective is to evaluate the effect of transfusion on outcomes
• Pregnancy in female Veterans
• Veteran is a prisoner or in custody of law enforcement
• Prior randomization in the CSP#599
• Patients who are known to have tested positive for COVID-19 and have not recovered prior to consent will not be consented. Any participant who is known to have a positive COVID-19 test during the screening process and has not recovered will be excluded prior to randomization.

Sponsors & Collaborators

• VA Office of Research and Development: lead

Study Sites (16)

Central Arkansas VHS John L. McClellan Memorial Veterans Hospital, Little Rock, AR

Little Rock, Arkansas, 72205-5484, United States

Location

VA Loma Linda Healthcare System, Loma Linda, CA

Loma Linda, California, 92357, United States

Location

VA Long Beach Healthcare System, Long Beach, CA

Long Beach, California, 90822, United States

Location

VA Palo Alto Health Care System, Palo Alto, CA

Palo Alto, California, 94304-1290, United States

Location

San Francisco VA Medical Center, San Francisco, CA

San Francisco, California, 94121, United States

Location

North Florida/South Georgia Veterans Health System, Gainesville, FL

Gainesville, Florida, 32608, United States

Location

James A. Haley Veterans' Hospital, Tampa, FL

Tampa, Florida, 33612, United States

Location

Minneapolis VA Health Care System, Minneapolis, MN

Minneapolis, Minnesota, 55417, United States

Location

VA Western New York Healthcare System, Buffalo, NY

Buffalo, New York, 14215, United States

Location

Asheville VA Medical Center, Asheville, NC

Asheville, North Carolina, 28805, United States

Location

Louis Stokes VA Medical Center, Cleveland, OH

Cleveland, Ohio, 44106, United States

Location

VA Portland Health Care System, Portland, OR

Portland, Oregon, 97239, United States

Location

VA Pittsburgh Healthcare System University Drive Division, Pittsburgh, PA

Pittsburgh, Pennsylvania, 15240, United States

Location

VA North Texas Health Care System Dallas VA Medical Center, Dallas, TX

Dallas, Texas, 75216, United States

Location

Michael E. DeBakey VA Medical Center, Houston, TX

Houston, Texas, 77030, United States

Location

VA Puget Sound Health Care System Seattle Division, Seattle, WA

Seattle, Washington, 98108, United States

Location

Related Publications (4)

• Kougias P, Sharath SE, Zhan M, Carson JL, Norman LE, Mi Z, Pal R, Dosluoglu H, Modrall JG, Sarosi GA Jr, Nelson P, Arya S, Scrymgeour A, Ollison J, Calais LA, Nambi V, Gregg LP, Abdullah SM, Tsai S, Becker N, Choi JC, Chiu L, Scali S, Barshes NR, Awad S, Moursi M, Koopmann MC, Sally M, Ihnat D, Ramaswamy A, Gasper W, Tzeng E, Wilson MA, Tang G, Huang G, Biswas K; TOP Trial Investigators. Liberal or Restrictive Postoperative Transfusion in Patients at High Cardiac Risk: The TOP Randomized Clinical Trial. JAMA. 2025 Dec 23;334(24):2197-2207. doi: 10.1001/jama.2025.20841.

  PMID: 41205227 RESULT

• Carson JL, Stanworth SJ, Dennis JA, Fergusson DA, Pagano MB, Roubinian NH, Turgeon AF, Valentine S, Trivella M, Doree C, Hebert PC. Transfusion thresholds and other strategies for guiding red blood cell transfusion. Cochrane Database Syst Rev. 2025 Oct 20;10(10):CD002042. doi: 10.1002/14651858.CD002042.pub6.

  PMID: 41114449 DERIVED

• Kougias P, Mi Z, Zhan M, Carson JL, Dosluoglu H, Nelson P, Sarosi GA Jr, Arya S, Norman LE, Sharath S, Scrymgeour A, Ollison J, Calais LA, Biswas K. Transfusion trigger after operations in high cardiac risk patients (TOP) trial protocol. Protocol for a multicenter randomized controlled transfusion strategy trial. Contemp Clin Trials. 2023 Mar;126:107095. doi: 10.1016/j.cct.2023.107095. Epub 2023 Jan 20.

  PMID: 36690072 DERIVED

• Carson JL, Stanworth SJ, Dennis JA, Trivella M, Roubinian N, Fergusson DA, Triulzi D, Doree C, Hebert PC. Transfusion thresholds for guiding red blood cell transfusion. Cochrane Database Syst Rev. 2021 Dec 21;12(12):CD002042. doi: 10.1002/14651858.CD002042.pub5.

  PMID: 34932836 DERIVED

MeSH Terms

Conditions

Myocardial Infarction; Acute Kidney Injury

Interventions

Blood Transfusion

Condition Hierarchy (Ancestors)

Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Infarction; Ischemia; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Necrosis; Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Biological Therapy; Therapeutics

Results Point of Contact

• Title: Panagiotis Kougias
• Organization: New York Veterans Affairs Healthcare System, Brooklyn

panagiotis.kougias@va.gov

718-836-6600

Study Officials

• Panagiotis Kougias, MD MSc

  VA New York Harbor Health Care System, Brooklyn Campus

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: FED
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 7, 2017
• First Posted: July 26, 2017
• Study Start: February 5, 2018
• Primary Completion: June 2, 2023
• Study Completion: March 2, 2024
• Last Updated: November 21, 2025
• Results First Posted: September 5, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (16)