Safety and Effectiveness of Two Blood Transfusion Strategies in Surgical Patients With Cardiovascular Disease

NCT ID: NCT00071032

Last Updated: 2020-11-16

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

2016 participants

Study Classification

INTERVENTIONAL

Study Start Date

2003-07-31

Study Completion Date

2009-05-31

Brief Summary

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The purpose of this study is to compare liberal red blood cell transfusion therapy with restrictive red blood cell transfusion therapy in surgical patients with cardiovascular disease or risk factors.

Detailed Description

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BACKGROUND:

Red blood cell transfusions are an extremely common medical intervention in both the United States and worldwide; over 14 million units of blood are transfused in the United States. Between 60 and 70 percent of all blood is transfused in the surgical setting. Despite the common use of red blood cell transfusions, the threshold for transfusion has not been adequately evaluated and is very controversial. A decade ago, the standard of care was to administer a peri-operative transfusion whenever the hemoglobin (Hgb) level fell below 10 g/dl (the "10/30 rule"). Concerns about the safety of blood, especially with respect to HIV and hepatitis, and the absence of data to support a 10 g/dl threshold led to the current standard of care, which is to administer blood transfusions based on the presence of symptoms, and not a specific Hgb/hematocrit level. However, there have not been any randomized clinical trials done with surgical patients that have tested the efficacy and safety of withholding blood until the patient develops symptoms, or the "10/30" approach to transfusion. Patients with underlying cardiovascular disease are at greatest risk of adverse effects from reduced Hgb levels.

DESIGN NARRATIVE:

This is a multi-center randomized trial to test the effectiveness of a transfusion strategy that maintains postoperative Hgb levels above 10 g/dl (liberal transfusion) in improving patient outcome. This will be compared to the restrictive (symptomatic) transfusion strategy in which blood transfusion is withheld until the patient develops symptoms of anemia or Hgb less than 8 g/dL. Participants will be randomly assigned to one of the two transfusion strategies. The liberal (10 g/dl) threshold strategy will use enough red blood cell units to maintain Hgb levels at or above 10 g/dl through hospital discharge. Restrictive (Symptomatic) transfusion strategy patients will receive red blood cell transfusions for symptoms of anemia, although transfusion is also permitted, but not required, if the Hgb level falls below 8 g/dl. Outcomes will include functional recovery (primary outcome: ability to walk 10 feet across a room without human assistance or death 60 days post-randomization), lower extremity activities of daily living and instrumental activities of daily living, survival up to 60-days and long-term, disposition (i.e., nursing home placement), and postoperative complications (e.g., myocardial infarction, unstable angina, or death in hospital, pneumonia, wound infection, thromboembolism, stroke).

Ambulation at 60 days is known to be highly predictive of ultimate functional outcome as well as of mortality at one year. Because inability to walk has such important implications for quality of life, and because it is a common problem, it far outweighs the small risk of viral infection or other complications from transfusion in elderly patients.

The trial will also evaluate the effect of transfusion threshold on postoperative risk of acute cardiac ischemia. The strategy will be to enhance surveillance for ischemic events by increasing the number of EKG and serum troponin measurements beyond those already called for in the original FOCUS protocol.

There is an ancillary study to the trial (R01 HL085706) to examine delirium as an outcome in a subsample of 139 patients. We will assess short-term (in hospital) and longer-term (after 30 days) severity of delirium.

Conditions

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Anemia Hematologic Diseases Cardiovascular Diseases Heart Diseases Myocardial Infarction Thromboembolism Pneumonia Cerebrovascular Accident

Keywords

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Blood Disease blood transfusion

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

SINGLE

Outcome Assessors

Study Groups

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Liberal (10 g/dL) Transfusion Strategy

Transfusion strategy that maintains postoperative Hgb levels above 10 g/dL.

Group Type EXPERIMENTAL

Liberal (10 g/dL) Transfusion Strategy

Intervention Type BIOLOGICAL

This transfusion strategy will maintains postoperative Hgb levels above 10 g/dL. This threshold strategy will use enough red blood cell units to maintain Hgb levels at or above 10 g/dL through hospital discharge or up to 30 days after randomization.

2

Symptomatic transfusion strategy, a more conservative strategy, in which blood transfusion is withheld until the patient develops symptoms of anemia.

Group Type ACTIVE_COMPARATOR

Restrictive (Symptomatic) Transfusion Strategy

Intervention Type BIOLOGICAL

Transfusion is withheld until the patient develops symptoms from anemia (i.e., chest pain or ECG changes thought to be ischemic, congestive heart failure, unexplained tachycardia or hypotension unresponsive to fluids) or until the hemoglobin level falls below 8 g/dL. Transfusion is permitted, but is not mandatory, if the hemoglobin level falls below 8 g/dL.

Interventions

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Liberal (10 g/dL) Transfusion Strategy

This transfusion strategy will maintains postoperative Hgb levels above 10 g/dL. This threshold strategy will use enough red blood cell units to maintain Hgb levels at or above 10 g/dL through hospital discharge or up to 30 days after randomization.

Intervention Type BIOLOGICAL

Restrictive (Symptomatic) Transfusion Strategy

Transfusion is withheld until the patient develops symptoms from anemia (i.e., chest pain or ECG changes thought to be ischemic, congestive heart failure, unexplained tachycardia or hypotension unresponsive to fluids) or until the hemoglobin level falls below 8 g/dL. Transfusion is permitted, but is not mandatory, if the hemoglobin level falls below 8 g/dL.

Intervention Type BIOLOGICAL

Eligibility Criteria

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Inclusion Criteria

* Has undergone surgical repair for a hip fracture
* Has a postoperative Hgb level below 10 g/dL within three days of surgery
* Diagnosis of cardiovascular disease (e.g., coronary artery disease, congestive heart failure, stroke or transient ischemic attack, or peripheral vascular disease) or cardiovascular risk factors (e.g., diabetes mellitus, hypertension, hypercholesterolemia, tobacco use, or creatinine levels greater than 2.0 mg/dL)

Exclusion Criteria

* Unable to walk prior to hip fracture
* Declines blood transfusions
* Suffered multiple traumas
* Pathologic fracture of the hip due to malignancy
* Clinically recognized acute myocardial infarction within the 30 days prior to study entry
* Previously participated in the trial and fractured the other hip
* Symptoms associated with anemia (e.g., ischemic chest pain) or actively bleeding at the time of randomization
Minimum Eligible Age

50 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Heart, Lung, and Blood Institute (NHLBI)

NIH

Sponsor Role collaborator

Rutgers, The State University of New Jersey

OTHER

Sponsor Role lead

Responsible Party

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Jeffrey L Carson, MD

Jeffrey L Carson

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Jeffrey L. Carson, MD

Role: STUDY_CHAIR

University Medicine & Dentistry of NJ

Michael Terrin

Role: PRINCIPAL_INVESTIGATOR

University of Maryland, College Park

Locations

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University Medicine & Dentistry of NJ

New Brunswick, New Jersey, United States

Site Status

Countries

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United States

References

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Carson JL, Terrin ML, Magaziner J, Chaitman BR, Apple FS, Heck DA, Sanders D; FOCUS Investigators. Transfusion trigger trial for functional outcomes in cardiovascular patients undergoing surgical hip fracture repair (FOCUS). Transfusion. 2006 Dec;46(12):2192-206. doi: 10.1111/j.1537-2995.2006.01056.x. No abstract available.

Reference Type BACKGROUND
PMID: 17176334 (View on PubMed)

Carson JL, Terrin ML, Noveck H, Sanders DW, Chaitman BR, Rhoads GG, Nemo G, Dragert K, Beaupre L, Hildebrand K, Macaulay W, Lewis C, Cook DR, Dobbin G, Zakriya KJ, Apple FS, Horney RA, Magaziner J; FOCUS Investigators. Liberal or restrictive transfusion in high-risk patients after hip surgery. N Engl J Med. 2011 Dec 29;365(26):2453-62. doi: 10.1056/NEJMoa1012452. Epub 2011 Dec 14.

Reference Type RESULT
PMID: 22168590 (View on PubMed)

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:CD002042. doi: 10.1002/14651858.CD002042.pub6.

Reference Type DERIVED
PMID: 41114449 (View on PubMed)

Zhang J, Chen Z, He Y. Comparison of liberal versus restrictive transfusion strategies after hip surgery in patients with coronary artery disease: a post hoc analysis of the FOCUS trial. BMC Cardiovasc Disord. 2024 Sep 18;24(1):498. doi: 10.1186/s12872-024-04151-z.

Reference Type DERIVED
PMID: 39294606 (View on PubMed)

Meng L, Wang X, Carson JL, Schlussel Y, Shapses SA. Vitamin D Binding Protein and Postsurgical Outcomes and Tissue Injury Markers After Hip Fracture: A Prospective Study. J Clin Endocrinol Metab. 2023 Dec 21;109(1):e18-e24. doi: 10.1210/clinem/dgad502.

Reference Type DERIVED
PMID: 37633261 (View on PubMed)

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.

Reference Type DERIVED
PMID: 34932836 (View on PubMed)

Carson JL, Sieber F, Cook DR, Hoover DR, Noveck H, Chaitman BR, Fleisher L, Beaupre L, Macaulay W, Rhoads GG, Paris B, Zagorin A, Sanders DW, Zakriya KJ, Magaziner J. Liberal versus restrictive blood transfusion strategy: 3-year survival and cause of death results from the FOCUS randomised controlled trial. Lancet. 2015 Mar 28;385(9974):1183-9. doi: 10.1016/S0140-6736(14)62286-8. Epub 2014 Dec 9.

Reference Type DERIVED
PMID: 25499165 (View on PubMed)

Other Identifiers

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U01HL073958-06

Identifier Type: NIH

Identifier Source: secondary_id

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U01HL073958

Identifier Type: NIH

Identifier Source: secondary_id

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U01HL074815

Identifier Type: NIH

Identifier Source: secondary_id

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159

Identifier Type: -

Identifier Source: org_study_id