Safety and Effectiveness of Two Blood Transfusion Strategies in Surgical Patients With Cardiovascular Disease (FOCUS)
|Anemia Hematologic Diseases Cardiovascular Diseases Heart Diseases Myocardial Infarction Thromboembolism Pneumonia Cerebrovascular Accident||Biological: Liberal (10 g/dL) Transfusion Strategy Biological: Restrictive (Symptomatic) Transfusion Strategy||Phase 3|
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single Blind (Outcomes Assessor)
Primary Purpose: Treatment
|Official Title:||Functional Outcomes in Cardiovascular Patients Undergoing Surgical Hip Fracture Repair (FOCUS)|
- Inability to Walk 10 Feet or Across a Room Without Human Assistance or Death [ Time Frame: 60 days after randomization ]ascertained via telephone follow-up
- Myocardial Infarction, Unstable Angina, or Death for Any Reason [ Time Frame: In-hospital ]
- Postoperative Complications (e.g., Pneumonia, Wound Infection, Thromboembolism, Stroke) [ Time Frame: In hospital ]
- Survival [ Time Frame: 30-daym, 60- day and long term up to 5 years ]
- Disposition Status (i.e., Nursing Home Placement) [ Time Frame: 60 days ]
- Function (e.g., Lower Extremity Activities of Daily Living, Instrumental Activities of Daily Living, Fatigue/Energy) [ Time Frame: 30 and 60 days ]
- Length of Stay in Hospital [ Time Frame: In-hospital ]
- Myocardial Infarction [ Time Frame: In-hospital ]
- Composite Outcomes (a) Death, Myocardial Infarction, and Pneumonia and b) Death, Myocardial Infarction, Pneumonia, Thromboembolism and Stroke) [ Time Frame: In-hospital ]
|Study Start Date:||July 2003|
|Study Completion Date:||May 2009|
|Primary Completion Date:||May 2009 (Final data collection date for primary outcome measure)|
Experimental: Liberal (10 g/dL) Transfusion Strategy
Transfusion strategy that maintains postoperative Hgb levels above 10 g/dL.
Biological: 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.
Active Comparator: 2
Symptomatic transfusion strategy, a more conservative strategy, in which blood transfusion is withheld until the patient develops symptoms of anemia.
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.
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.
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00071032
|United States, New Jersey|
|University Medicine & Dentistry of NJ|
|New Brunswick, New Jersey, United States, 08903|
|Study Chair:||Jeffrey L. Carson, MD||University Medicine & Dentistry of NJ|
|Principal Investigator:||Michael Terrin||University of Maryland|