Liberal Transfusion Strategy in Elderly Patients

Study Overview
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Brief Summary
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In this prospective, multicentre, open, randomised, controlled clinical trial elderly patients (≥ 70 years) undergoing intermediate- or high-risk non-cardiac surgery will be randomised either to a liberal group (patients receive a RBC unit each time Hb falls ≤ 9 g/dl (≤ 5.6mmol/l) with a target range for the post-transfusion Hb level of 9-10.5 g/dl (5.6-6.5 mmol/l)) or restrictive group (patients receive a single RBC unit each time Hb falls ≤ 7.5 g/dl (≤ 4.7 mmol/l) with a target range for the post-transfusion Hb level of 7.5-9 g/dl (4.7-5.6 mmol/l). Primary efficacy endpoint: is a composite of death from any cause and anaemia-associated, ischaemic events (defined as acute myocardial infarction, acute ischaemic stroke, acute kidney injury stage III, acute mesenteric ischaemia, acute peripheral vascular ischaemia) within 90 days after surgery.

Official Title
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Liberal Transfusion Strategy to Prevent Mortality and Anaemia-associated, Ischaemic Events in Elderly Non-cardiac Surgical Patients

Conditions
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Anemia, Transfusion-dependent Anemia, Surgery

Intervention / Treatment
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* Drug: red blood cell transfusion trigger


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients ≥ 70 years of age scheduled for intermediate- or high-risk non-cardiac surgery will be registered Registered patients will be randomised only if they indeed develop severe anaemia (if Hb level falls ≤ 9 g/dl) during surgery (=day 0) or day 1, 2, or 3 after surgery Exclusion Criteria: preoperative Hb level ≤ 9 g/dl chronic kidney disease requiring dialysis suspected lack of compliance with follow-up procedures participation in other interventional trials expected death within 3 months inability to provide informed consent with absence of a legally authorised representative/ legal guardian temporary inability to provide informed consent previous participation in our trial patients who are prevented from having blood and blood products according to a system of beliefs (e.g. Jehovah's Witnesses) preoperative autologous blood donation.

Ages Eligible for Study
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Minimum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Liberal<br>Liberal group (patients receive a RBC unit each time Hb falls ≤ 9 g/dl (≤ 5.6mmol/l) with a target range for the post-transfusion Hb level of 9-10.5 g/dl (5.6-6.5 mmol/l)). | Drug: red blood cell transfusion trigger<br>* patients receive a RBC unit with different target ranges for the post-transfusion Hb levels<br>|
| Active Comparator: Restrictive<br>Restrictive group (patients receive a single RBC unit each time Hb falls ≤ 7.5 g/dl (≤ 4.7 mmol/l) with a target range for the post-transfusion Hb level of 7.5-9 g/dl (4.7-5.6 mmol/l). | Drug: red blood cell transfusion trigger<br>* patients receive a RBC unit with different target ranges for the post-transfusion Hb levels<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Occurrence of a composite endpoint | Composite of death and anaemia-associated events I. All-cause mortality defined as death from any cause. II. Acute myocardial infarction confirmed by a cardiologist III. Acute ischaemic stroke confirmed by a neurologist IV. Acute kidney injury (stage III) defined according to the Kidney Disease Improving Global Outcomes criteria: Increase of plasma creatinine level ≥ 3 times within a time window of 7 days or initiation of renal replacement therapy. V. Acute mesenteric ischaemia defined as ischaemia confirmed by intervention (abdominal surgery or mesenteric angiography). VI. Acute peripheral vascular ischaemia defined as a new non-thrombotic compromised circulation in a limb confirmed by angiography and/or leading to surgery. | 90 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of patients receiving red blood cell transfusion |  | hospital discharge (an anticipated average of 10 days) | 
| Number of red blood cell units transfused |  | hospital discharge (an anticipated average of 10 days) | 
| Total length of stay in the intensive care unit |  | hospital discharge (an anticipated average of 10 days) | 
| Total length of stay in hospital |  | hospital discharge (an anticipated average of 10 days) | 
| Number of participants with acute kidney injury stage I-II | The occurrence of acute kidney injury (stage I or II) defined according to the Kidney Disease Improving Global Outcomes criteria (stage I: increase of plasma creatinine level ≥ 1.5-1.9 times baseline or ≥ 0.3mg/dl within 48 hours; stage II: increase of plasma creatinine level ≥ 2-2.9 times baseline within a time window of 7 days) during the initial hospital stay | hospital discharge (an anticipated average of 10 days) | 
| Time to infection | Time to (first) infection (infection requiring therapeutic intravenous antibiotic treatment (pneumonia, wound infection, sepsis, central line associated blood stream infection)) during the initial hospital stay or leading to hospital re-admission | 90 days | 
| Time to re-hospitalisation | Time to (first) re-hospitalisation | 90 days | 
| functional status (Barthel index) | Functional status (assessed by Barthel Index) | 90 days | 
| Health-related quality of life | Health-related quality of life (assessed by EuroQoL EQ-5D and 12-item World Health Organisation Disability Assessment Schedule WHODAS 2.043) by telephone questionnaire) | 90 days | 
| Occurrence of any individual component of the composite | composite components (all-cause mortality, acute myocardial infarction, acute stroke, acute kidney injury stage III, acute mesenteric ischaemia, and/or acute peripheral vascular ischaemia) | 1 year |