Transfusion Strategies for Cardiac Surgery Patients

(TRICS-IV Trial)

Recruiting at 59 trial locations

Overseen By David Mazer, MD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Unity Health Toronto

Disqualifiers: Refuse blood products, Heart transplant, Pregnancy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

Duration: Up to hospital discharge or after 28 days postoperatively, whichever comes first

1440 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores two different blood transfusion strategies for individuals undergoing heart surgery with a heart-lung machine. The goal is to determine which strategy benefits those at moderate to high risk of complications during surgery. It compares a more liberal transfusion strategy, where transfusions occur at higher blood levels, to a more restrictive one, with transfusions at lower blood levels. Individuals undergoing heart surgery with a heart-lung machine and possessing a higher risk score for complications may be suitable candidates for this study. As an unphased trial, it offers participants the chance to contribute to important research that could enhance surgical outcomes for future patients.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that both more and fewer red blood cell transfusions are generally safe for heart surgery patients. Studies indicate that fewer transfusions are as safe as more. For instance, one study found that the risk of major heart problems was similar for both approaches.

Another study reported nearly identical main results for fewer versus more transfusions, with an odds ratio of 0.90, indicating similar safety levels. This suggests that patients receiving fewer transfusions did not face a higher risk of complications compared to those receiving more.

Both methods have been used in patients with heart disease, and neither has led to a significant increase in negative outcomes. Thus, whether patients receive more or fewer blood transfusions, the safety results are generally comparable. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about the transfusion strategies being tested for cardiac surgery patients because they have the potential to tailor blood transfusions more precisely. Unlike current standard approaches, which often follow a one-size-fits-all protocol, the liberal transfusion strategy allows for transfusions at higher hemoglobin levels, potentially improving patient stability in critical care settings. Conversely, the restrictive strategy limits transfusions to lower hemoglobin levels, which might reduce complications from unnecessary transfusions. This trial could lead to more personalized care, improving outcomes by balancing the benefits and risks of transfusions more effectively.

What evidence suggests that this trial's transfusion strategies could be effective for cardiac surgery patients?

This trial compares two main strategies for managing red blood cell (RBC) transfusions during heart surgery: the liberal transfusion strategy and the restrictive transfusion strategy. In the restrictive transfusion strategy arm, transfusions occur only when hemoglobin levels are very low. Studies have found this approach to be as effective as the liberal transfusion strategy, which involves more frequent transfusions, in preventing major heart problems. One study found that the restrictive strategy reduces the number of transfusions needed without increasing the risk of death. However, the liberal strategy can lower the risk of heart attacks but might increase the chance of lung injury. Both strategies are effective, each with its own pros and cons. ^{1 5 6 7 8}

Who Is on the Research Team?

Nadine Shehata, MD

Principal Investigator

MOUNT SINAI HOSPITAL

David Mazer, MD

Principal Investigator

Unity Health Toronto

Are You a Good Fit for This Trial?

This trial is for younger patients (18-65 years old) with a moderate to high risk of complications from cardiac surgery, as indicated by a EuroSCORE I of 6 or more. They must be undergoing heart surgery that requires cardiopulmonary bypass and able to give informed consent. It's not for those who refuse blood products, are in certain pre-surgery donation programs, need a heart transplant or ventricular assist device alone, or women who are pregnant or breastfeeding.

Inclusion Criteria

Preoperative European System for Cardiac Operative Risk Evaluation (EuroSCORE I) of 6 or more

Planned cardiac surgery using cardiopulmonary bypass

Informed consent obtained

Exclusion Criteria

You can't or won't receive blood products.

Patients who are involved in a preoperative autologous pre-donation program

Patients who are having a heart transplant or having surgery solely for an insertion of a ventricular assist device

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo cardiac surgery with either a restrictive or liberal transfusion strategy

Up to hospital discharge or after 28 days postoperatively, whichever comes first

Follow-up

Participants are monitored for safety and effectiveness after treatment, including incidence of infection, acute kidney injury, and other secondary outcomes

Up to 6 months after cardiac surgery

Long-term follow-up

Monitoring of primary outcomes such as all-cause mortality, myocardial infarction, and new onset renal failure requiring dialysis

Within 6 months after cardiac surgery

What Are the Treatments Tested in This Trial?

Interventions

• Liberal transfusion strategy
• Restrictive Transfusion Strategy

Trial Overview The TRICS-IV study compares two blood transfusion strategies during cardiac surgery: 'Restrictive' gives fewer transfusions based on specific criteria while 'Liberal' provides them more freely. Patients will be randomly assigned to one of these approaches to see which is superior for those under 65 at higher surgical risk.

How Is the Trial Designed?

Group I: Restrictive Transfusion Strategy Active Control 1 Intervention

Patients will receive a RBC transfusion if their Hb concentration is \<75 g/L (\<7.5 g/dL; \<4.7mmol/L) intraoperatively and/or postoperatively.

Group II: Liberal Transfusion Strategy Active Control 1 Intervention

Patients will receive a RBC transfusion if their Hb concentration is \<95 g/L (\<9.5 g/dL; \<5.9mmol/L) intraoperatively, or postoperatively in the ICU; and/or \<85 g/L (\< 8.5 g/dL; \<5.3mmol/L) on the ward.

Who Is Running the Clinical Trial?

Unity Health Toronto

Lead Sponsor

Trials

572

Recruited

470,000+

Published Research Related to This Trial

A systematic review of four randomized controlled trials involving 454 pediatric cardiac surgery patients found no significant differences in clinical outcomes, such as ICU stay and hospital length, between restrictive and liberal red blood cell transfusion strategies.

The study suggests that restrictive transfusion thresholds are non-inferior to liberal thresholds in pediatric cardiac patients, indicating that a more conservative approach may be safe, but further high-quality research is needed to confirm these findings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Red blood cell transfusion threshold after pediatric cardiac surgery: A systematic review and meta-analysis. Deng, X., Wang, Y., Huang, P., et al.[2022]

In a review of ten trials involving 9,101 patients, a restrictive blood transfusion strategy in cardiac surgery did not significantly affect mortality rates compared to a liberal strategy, indicating it is a safe alternative.

The restrictive strategy led to a lower number of red blood cell transfusions without negatively impacting other clinical outcomes, suggesting it can effectively reduce the need for transfusions in these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effect of restrictive versus liberal transfusion strategies on longer-term outcomes after cardiac surgery: a systematic review and meta-analysis with trial sequential analysis. Kashani, HH., Lodewyks, C., Kavosh, MS., et al.[2022]

Restrictive transfusion strategies, which involve lower hemoglobin thresholds for red cell transfusion, are not inferior to liberal strategies in patients undergoing cardiac surgery, suggesting they can be safely implemented.

Recent large randomized controlled trials have shown inconsistent results regarding hemoglobin levels and transfusion practices, but overall evidence supports the use of restrictive strategies to reduce risks of anemia and transfusion-related complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Red cell transfusion in cardiac surgery: what is the right balance? Shehata, N., Mazer, CD.[2019]

In a study of 5243 adults undergoing cardiac surgery, a restrictive red-cell transfusion strategy was found to be noninferior to a liberal strategy regarding major adverse outcomes (death, myocardial infarction, stroke, or new-onset renal failure) at 6 months post-surgery.

Mortality rates were similar between the restrictive (6.2%) and liberal (6.4%) transfusion groups, indicating that a more conservative approach to transfusion does not compromise patient safety or outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Six-Month Outcomes after Restrictive or Liberal Transfusion for Cardiac Surgery. Mazer, CD., Whitlock, RP., Fergusson, DA., et al.[2018]

A review of literature on blood transfusions in cardiac operations indicates that a restrictive transfusion policy is safe and effective, showing little difference in outcomes compared to a liberal policy while also reducing costs.

While many patients may not need transfusions, a small group of high-risk patients might benefit from a more liberal approach, although identifying these patients remains challenging.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Case for a Conservative Approach to Blood Transfusion Management in Cardiac Surgery. Gunn, T., Paone, G., Emery, RW., et al.[2022]

Excess blood transfusions during cardiac surgery can lead to serious complications such as infections, immune system issues, and lung injuries, which are often underreported and underestimated in their impact.

A restrictive transfusion strategy, which uses fewer transfusions, has been shown in randomized trials to be as effective or even better than a liberal transfusion strategy, yet it faces resistance in adoption within the cardiac surgical community.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Blood Conservation in Cardiac Surgery: In Need of a Transfusion Revolution. Varghese, R., Jhang, J.[2017]

A restrictive transfusion protocol, which only allows red blood cell transfusions for patients with hemoglobin levels below 6 g/dL or between 6 to 8 g/dL with specific conditions, was safely implemented in a study of 409 cardiac surgery patients across 30 centers.

The protocol resulted in excellent patient outcomes, with a low mortality rate of 0.49% and a significant portion (65.0%) of patients avoiding transfusions altogether, suggesting that this approach can effectively reduce unnecessary transfusions while maintaining safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safe application of a restrictive transfusion protocol in moderate-risk patients undergoing cardiac operations. Song, HK., von Heymann, C., Jespersen, CM., et al.[2014]

A review of over 7000 patients in clinical trials indicates that a restrictive transfusion strategy (7-8 g/dL) is generally safe and may be superior to a liberal strategy (9-10 g/dL) for most patients.

However, for patients with specific conditions like myocardial infarction or stroke, more research is needed, as preliminary evidence suggests that a liberal transfusion strategy could be beneficial.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transfusion strategies in hematologic and nonhematologic disease. Carson, JL., Strair, R.[2016]

In a study involving 5243 adults undergoing cardiac surgery, a restrictive red-cell transfusion strategy (transfusing at hemoglobin <7.5 g/dL) was found to be noninferior to a liberal strategy (transfusing at hemoglobin <9.5 g/dL) in terms of major clinical outcomes, such as death, myocardial infarction, stroke, or new-onset renal failure.

The restrictive strategy resulted in significantly fewer patients receiving blood transfusions (52.3% vs. 72.6%), suggesting it is a safer approach that conserves blood resources without compromising patient safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Restrictive or Liberal Red-Cell Transfusion for Cardiac Surgery. Mazer, CD., Whitlock, RP., Fergusson, DA., et al.[2018]

Citations

1. nejm.org nejm.org/doi/full/10.1056/NEJMoa1711818

Restrictive or Liberal Red-Cell Transfusion for Cardiac ... Red-cell transfusion occurred in 52.3% of the patients in the restrictive-threshold group, as compared with 72.6% of those in the liberal- ...

2. jamanetwork.com jamanetwork.com/journals/jama/fullarticle/2776201

Effect of a Restrictive vs Liberal Blood Transfusion Strategy ... A restrictive transfusion strategy compared with a liberal strategy resulted in a noninferior rate of major cardiovascular events among patients with acute ...

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/41114449

Transfusion thresholds and other strategies for guiding red ... A restrictive transfusion strategy significantly decreased the proportion of adults and children exposed to RBC transfusion.

4. ashpublications.org ashpublications.org/blood/article/146/6/661/537046/Counterpoint-the-design-and-interpretation-of

the design and interpretation of blood transfusion randomized ... The primary outcome of 30-day all-cause mortality was 18.7% in the restrictive strategy, and 23.3% in the liberal strategy (absolute difference, ...

5. frontiersin.org frontiersin.org/journals/cardiovascular-medicine/articles/10.3389/fcvm.2025.1457400/full

Liberal versus restrictive red blood cell transfusion strategy ... Our meta-analysis demonstrated that a liberal RBC transfusion strategy reduced the risk of MI and increased the risk of acute lung injury.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6441852/

Restrictive compared with liberal red cell transfusion ... The current evidence suggests restrictive transfusion strategies are not inferior to liberal transfusion strategies in adult and pediatric patients undergoing ...

7. ahajournals.org ahajournals.org/doi/10.1161/CIRCOUTCOMES.124.010957

Risks of Restrictive Versus Liberal Red Blood Cell ... Risks of restrictive versus liberal red blood cell transfusion strategies in patients with cardiovascular disease: an updated meta-analysis.

8. nejm.org nejm.org/doi/full/10.1056/NEJMoa2307983

Restrictive or Liberal Transfusion Strategy in Myocardial ... In patients with acute myocardial infarction and anemia, a liberal transfusion strategy did not significantly reduce the risk of recurrent myocardial ...