Liberal Transfusion Strategy in Elderly Patients (LIBERAL)

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

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.

Study Overview

• Status: Recruiting
• Conditions: Anemia; Surgery; Transfusion-dependent Anemia
• Intervention / Treatment: Drug: red blood cell transfusion trigger

• Study Type: Interventional
• Enrollment (Estimated): 2470
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Patrick Meybohm, MD; Phone Number: 004993120130001; Email: meybohm_p@ukw.de

Study Locations

• Germany
  • Augsburg, Germany
    • Recruiting
    • University Hospital Augsburg
    • Contact: Ulrich Jaschinski
    • Sub-Investigator: Maria Zanquilla
  • Berlin, Germany
    • Recruiting
    • Berlin Charite CCM
    • Contact: Stefan Schaller
    • Sub-Investigator: Sascha Tafelski
  • Berlin, Germany
    • Recruiting
    • Charite Berlin CBF
    • Contact: Sascha Treskatsch
    • Sub-Investigator: Christian Berger
  • Bonn, Germany
    • Recruiting
    • University Hospital Bonn
    • Contact: Markus Velten
    • Sub-Investigator: Maria Wittmann
  • Dortmund, Germany
    • Not yet recruiting
    • Klinikum Dortmund
    • Contact: Richard Ellerkmann
    • Sub-Investigator: Holger Pohl
  • Frankfurt, Germany
    • Recruiting
    • University Hospital Frankfurt
    • Contact: Kai Zacharowski
    • Sub-Investigator: Simone Lindau
  • Hamburg, Germany
    • Recruiting
    • University Hospital Hamburg
    • Contact: Lars Eichler
    • Sub-Investigator: Mark Punke
  • Jena, Germany
    • Recruiting
    • University Hospital Jena
    • Contact: Michael Bauer
    • Sub-Investigator: Frank Bloos
  • Kiel, Germany
    • Recruiting
    • University Hospital Schleswig-Holstein
    • Contact: Gunnar Elke
    • Sub-Investigator: Dirk Schädler
  • Mainz, Germany
    • Recruiting
    • University Hospital Mainz
    • Contact: Eva Wittenmeier
    • Sub-Investigator: Michael Schuster
  • Münster, Germany
    • Recruiting
    • University Hospital Munster
    • Contact: Alexander Zarbock
    • Sub-Investigator: Melanie Meersch
  • Münster, Germany
    • Recruiting
    • St. Franziskus Hospital Munster
    • Contact: Ullrich Göbel
    • Sub-Investigator: Andre Hemping-Bovenkerk
  • Regensburg, Germany
    • Recruiting
    • University Hospital Regensburg
    • Contact: Diane Bitzinger
    • Sub-Investigator: Karin Pfister
  • Würzburg, Germany, 97080
    • Recruiting
    • University Hospital Würzburg
    • Contact: Patrick Meybohm, MD; Phone Number: 004093120130001; Email: meybohm_p@ukw.de
    • Principal Investigator: Peter Kranke, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 70 years and older (Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Liberal; 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; patients receive a RBC unit with different target ranges for the post-transfusion Hb levels
Active Comparator: Restrictive; 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; patients receive a RBC unit with different target ranges for the post-transfusion Hb levels

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Johann Wolfgang Goethe University Hospital
• Collaborators: Wuerzburg University Hospital
• Investigators: Principal Investigator: Patrick Meybohm, MD, Wuerzburg University Hospital

Publications and helpful links

General Publications

• 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.
• Meybohm P, Lindau S, Treskatsch S, Francis R, Spies C, Velten M, Wittmann M, Gueresir E, Stoppe C, Kowark A, Coburn M, Selleng S, Baschin M, Jenichen G, Meersch M, Ermert T, Zarbock A, Kranke P, Kredel M, Helf A, Laufenberg-Feldmann R, Ferner M, Wittenmeier E, Gurtler KH, Kienbaum P, de Abreu MG, Sander M, Bauer M, Seyfried T, Gruenewald M, Choorapoikayil S, Mueller MM, Seifried E, Brosteanu O, Bogatsch H, Hasenclever D, Zacharowski K; LIBERAL Collaboration Group. Liberal transfusion strategy to prevent mortality and anaemia-associated, ischaemic events in elderly non-cardiac surgical patients - the study design of the LIBERAL-Trial. Trials. 2019 Feb 4;20(1):101. doi: 10.1186/s13063-019-3200-3.

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start (Actual): December 4, 2017
• Primary Completion (Estimated): December 31, 2024
• Study Completion (Estimated): December 31, 2025

Study Registration Dates

• First Submitted: November 27, 2017
• First Submitted That Met QC Criteria: December 8, 2017
• First Posted (Actual): December 11, 2017

Study Record Updates

• Last Update Posted (Estimated): March 5, 2024
• Last Update Submitted That Met QC Criteria: March 4, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Hematologic Diseases; Anemia
• Other Study ID Numbers: 139/17F

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No