Cost-effectiveness and Cost-utility of Liberal vs Restrictive Red Blood Cell Transfusion Strategies in Patients With Acute Myocardial Infarction and Anaemia. (REALITY)

April 4, 2022 updated by: Assistance Publique - Hôpitaux de Paris

Cost-effectiveness and Cost-utility of Liberal vs Restrictive Red Blood Cell Transfusion Strategies in Patients With Acute Myocardial Infarction and Anaemia. The REALITY (REstrictive And LIberal Transfusion Strategies in Patients With Acute mYocardial Infarction) Randomized Trial.

Anemia in patients with myocardial infarction (MI) is a relatively frequent issue, resulting in poorer outcome. There is equipoise regarding which transfusion strategy is best, and there is an international consensus on the urgent need for a randomized trial.

The investigators hypothesize that a "restrictive" transfusion strategy is at least non-inferior to a "liberal" transfusion strategy on 30-day outcomes of MI patients with anemia. Given the costs and risks of transfusion, a cost-effectiveness and cost-utility analysis becomes key to determining the role of each strategy.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Anemia is frequent in patients with myocardial infarction (MI). The antiplatelet and anticoagulant agents used for MI treatment increase the risk of bleeding, which in turn increases the risk of ischemia and mortality. Anemia is an independent predictor of cardiac events in this setting. In the "FAST-MI 2010" nationwide registry, the prevalence of anemia (defined as Hb <10g/dL) at admission was 3% and impacted mortality. Whether this risk can be overcome by transfusion is debated.

In theory, transfusion should increase oxygen delivery to the myocardium. However, recent data suggest that oxygen delivery is not increased in patients receiving transfusion, that red blood cells are rapidly depleted of nitric oxide during storage and that, conversely, transfusion may increase platelet activation and aggregation and these consequences appear potentially even more deleterious in patients with cardiovascular disease. In the general population without cardiovascular disease of medical and surgical patients, the role of liberal vs restrictive transfusion strategies has been explored by a series of randomized trials, which have led to a consensus to withhold blood transfusions until a threshold of 7 to 8 g/dl hemoglobin is reached.

Among patients with myocardial infarction, however, both the deleterious consequences of anemia and the risks of transfusion may be greater, which leads to lingering uncertainty regarding the role of liberal vs restrictive transfusion strategies in this setting. The clinical data are observational and contradictory. Conversely, a large meta-analysis (>200 000 patients) reported a higher risk of mortality and recurrent MI in MI patients who received transfusion. More recently, a careful observational study has shown that the majority of patients undergoing blood transfusion cannot be matched with non-transfused patients due to their markedly different clinical profiles, indicating that observational studies cannot reliable establish the benefits or risks of transfusion because they are hopelessly influenced by selection bias. These results strongly highlight the need for randomized trials to establish the role of transfusion during acute MI, a call for a randomized trial that has been echoed by several thought leaders in the field in recent years. Two small randomized trials (respectively 45 and 110 patients) comparing liberal vs. restrictive transfusion strategies in MI showed no clear difference in clinical outcomes but were both underpowered.

The only guideline regarding management of anemia in this setting is from the European Society of Cardiology (ESC) guidelines on non-ST segment elevation - acute coronary syndrome (NSTE-ACS), which advise blood transfusion only if the hemodynamic status is compromised or the hemoglobin level is <7g/dL. As a result, there is wide variation in clinical practice. There is therefore equipoise regarding which transfusion strategy is best.

Hypothesis:

We hypothesize that a "restrictive" transfusion strategy (triggered by Hb <= 8 g/ dL) will be clinically non-inferior to a "liberal" transfusion strategy (triggered by Hb <= 10g/ dL) but will be less costly.

Main objective:

The main objective of the study is to compare cost-effectiveness of restrictive (triggered by Hb <= 8 g/ dL) vs liberal (triggered by Hb <= 10g/ dL) red blood transfusion strategies for patients with acute MI and anemia (7g /dL < Hb <= 10g / dL).

Secondary objective(s):

  1. The key secondary objective is to perform cost-utility analyses at 30-days and 1 year.
  2. The main clinical objective will be to determine whether a restrictive transfusion strategy is clinically non-inferior to a liberal transfusion strategy in terms of major adverse cardiac events (MACE) at 30 days, defined as the composite of all-cause death, nonfatal stroke, nonfatal recurrent MI, and emergency revascularization prompted by ischemia.

2. A tertiary objective will be to compare major adverse cardiac events (MACE) at 1 year, since the impact of transfusion strategies on MACE may be delayed, or conversely, an initial benefit of either strategy may become lost over the first year.

Study Type

Interventional

Enrollment (Actual)

668

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • France
      • Paris, France
        • Hôpital Bichat
  • Spain
      • Barcelona, Spain, 08036
        • Hospital Clinic of Barcelona

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Aged ≥ 18 years
  • Recent acute myocardial infarction, with or without ST- segment elevation, with a combination of ischemic symptoms occurring in the past 48 hours,before the MI related admission, and elevation of biomarkers of myocardial injury (troponin)
  • Anemia Hb ≤ 10g / dL but > 7 g/dL on Hb, measured at any time during the index hospital admission for MI.
  • Written informed consent
  • Coverage for medical insurance.

Exclusion Criteria:

  • Shock (SBP < 90 mmHg with clinical signs of low output or patients requiring inotropic agents)
  • MI occurring post-percutaneous coronary intervention (PCI) or post-coronary artery bypass graft (CABG) (i.e. type IV or V Acute MI according to the 2012 Universal Definition of MI
  • Life-threatening or massive ongoing bleeding (as judged by the investigator)
  • Any blood transfusion in the previous 30-days
  • any known malignant hematologic disease Note: Sickle cell disease, thalassemia and anemia due to chronic renal failure (even under EPO) are not an exclusion criteria

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Supportive Care
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Restrictive transfusion strategy
Transfusions are withheld unless Hb is <= 8 g/dL, with a target Hb of 8 to 10 g /dL
Procedure: Restrictive transfusion
Transfusions are withheld unless Hb is <= 8 g/dL, with a target Hb of 8 to 10 g /dL
Biological: red blood transfusion
Experimental: Liberal transfusion strategy
Transfusions are allowed as soon as Hb <= 10 g/dL with a target of 11 g /dL.
Biological: red blood transfusion
Procedure: Liberal transfusion
transfusions are allowed as soon as Hb <= 10 g/dL with a target of 11 g /dL

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Cost-effectiveness ratio at 30 days
Time Frame: 30 days
The primary endpoint is the incremental cost-effectiveness ratio (ICER) at 30-days, using the composite endpoint (30-day composite of all-cause death, non fatal stroke, nonfatal recurrent MI, and emergency revascularization prompted by ischemia) as the effectiveness criterion
30 days

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Cost-effectiveness ratio at 1 year
Time Frame: 1 year
Incremental cost-effectiveness ratio (ICER) at 1 year, using the composite endpoint (1-year composite of all-cause death, non fatal stroke, nonfatal recurrent MI, and emergency revascularization prompted by ischemia) as the effectiveness criterion
1 year
Clinically non inferiority at 30 days
Time Frame: 30 days
The main clinical endpoint is Major Adverse Cardiac Events (MACE) at 30-days defined as the 30-day composite of all-cause death, non-fatal recurrent MI, non-fatal stroke and emergency revascularization prompted by ischemia, (all of the components of this composite clinical outcome will be analyzed separately as secondary endpoints of their own)
30 days
Clinically non inferiority at 1 year
Time Frame: 1 year
The main clinical endpoint is Major Adverse Cardiac Events (MACE) at 30-days defined as the 30-day composite of all-cause death, non-fatal recurrent MI, non-fatal stroke and emergency revascularization prompted by ischemia, (all of the components of this composite clinical outcome will be analyzed separately as secondary endpoints of their own)
1 year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Assistance Publique - Hôpitaux de Paris

Investigators

  • Principal Investigator: Philippe-Gabriel STEG, Assistance Publique - Hôpitaux de Paris

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 23, 2016

Primary Completion (Actual)

October 10, 2019

Study Completion (Actual)

September 10, 2020

Study Registration Dates

First Submitted

January 5, 2016

First Submitted That Met QC Criteria

January 5, 2016

First Posted (Estimate)

January 6, 2016

Study Record Updates

Last Update Posted (Actual)

April 12, 2022

Last Update Submitted That Met QC Criteria

April 4, 2022

Last Verified

March 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • K140705
  • 2015-A00360-49 (Other Identifier: ANSM)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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