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Liberal Transfusion Strategy in Elderly Patients (LIBERAL)

Primary Purpose

Transfusion-dependent Anemia, Surgery, Anemia

Status
Recruiting
Phase
Phase 3
Locations
Germany
Study Type
Interventional
Intervention
red blood cell transfusion trigger
Sponsored by
Johann Wolfgang Goethe University Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Transfusion-dependent Anemia

Eligibility Criteria

70 Years - undefined (Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • University Hospital AugsburgRecruiting
  • Berlin Charite CCMRecruiting
  • Charite Berlin CBFRecruiting
  • University Hospital BonnRecruiting
  • Klinikum Dortmund
  • University Hospital FrankfurtRecruiting
  • University Hospital HamburgRecruiting
  • University Hospital JenaRecruiting
  • University Hospital Schleswig-HolsteinRecruiting
  • University Hospital MainzRecruiting
  • St. Franziskus Hospital MünsterRecruiting
  • University Hospital MünsterRecruiting
  • University Hospital RegensburgRecruiting
  • University Hospital WürzburgRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Liberal

Restrictive

Arm Description

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)).

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).

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Proportion of patients receiving red blood cell transfusion
Number of red blood cell units transfused
Total length of stay in the intensive care unit
Total length of stay in hospital
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
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
Time to re-hospitalisation
Time to (first) re-hospitalisation
functional status (Barthel index)
Functional status (assessed by Barthel Index)
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)
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)

Full Information

First Posted
November 27, 2017
Last Updated
February 11, 2023
Sponsor
Johann Wolfgang Goethe University Hospital
Collaborators
Wuerzburg University Hospital
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1. Study Identification

Unique Protocol Identification Number
NCT03369210
Brief Title
Liberal Transfusion Strategy in Elderly Patients
Acronym
LIBERAL
Official Title
Liberal Transfusion Strategy to Prevent Mortality and Anaemia-associated, Ischaemic Events in Elderly Non-cardiac Surgical Patients
Study Type
Interventional

2. Study Status

Record Verification Date
February 2023
Overall Recruitment Status
Recruiting
Study Start Date
December 4, 2017 (Actual)
Primary Completion Date
December 31, 2024 (Anticipated)
Study Completion Date
December 31, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Johann Wolfgang Goethe University Hospital
Collaborators
Wuerzburg University Hospital

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Transfusion-dependent Anemia, Surgery, Anemia

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
InvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
2470 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Liberal
Arm Type
Experimental
Arm Description
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)).
Arm Title
Restrictive
Arm Type
Active Comparator
Arm Description
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).
Intervention Type
Drug
Intervention Name(s)
red blood cell transfusion trigger
Intervention Description
patients receive a RBC unit with different target ranges for the post-transfusion Hb levels
Primary Outcome Measure Information:
Title
Occurrence of a composite endpoint
Description
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.
Time Frame
90 days
Secondary Outcome Measure Information:
Title
Proportion of patients receiving red blood cell transfusion
Time Frame
hospital discharge (an anticipated average of 10 days)
Title
Number of red blood cell units transfused
Time Frame
hospital discharge (an anticipated average of 10 days)
Title
Total length of stay in the intensive care unit
Time Frame
hospital discharge (an anticipated average of 10 days)
Title
Total length of stay in hospital
Time Frame
hospital discharge (an anticipated average of 10 days)
Title
Number of participants with acute kidney injury stage I-II
Description
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
Time Frame
hospital discharge (an anticipated average of 10 days)
Title
Time to infection
Description
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
Time Frame
90 days
Title
Time to re-hospitalisation
Description
Time to (first) re-hospitalisation
Time Frame
90 days
Title
functional status (Barthel index)
Description
Functional status (assessed by Barthel Index)
Time Frame
90 days
Title
Health-related quality of life
Description
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)
Time Frame
90 days
Title
Occurrence of any individual component of the composite
Description
composite components (all-cause mortality, acute myocardial infarction, acute stroke, acute kidney injury stage III, acute mesenteric ischaemia, and/or acute peripheral vascular ischaemia)
Time Frame
1 year

10. Eligibility

Sex
All
Minimum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Patrick Meybohm, MD
Phone
004993120130001
Email
meybohm_p@ukw.de
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Patrick Meybohm, MD
Organizational Affiliation
Wuerzburg University Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
University Hospital Augsburg
City
Augsburg
Country
Germany
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Ulrich Jaschinski
First Name & Middle Initial & Last Name & Degree
Maria Zanquilla
Facility Name
Berlin Charite CCM
City
Berlin
Country
Germany
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Stefan Schaller
First Name & Middle Initial & Last Name & Degree
Sascha Tafelski
Facility Name
Charite Berlin CBF
City
Berlin
Country
Germany
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Sascha Treskatsch
First Name & Middle Initial & Last Name & Degree
Christian Berger
Facility Name
University Hospital Bonn
City
Bonn
Country
Germany
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Markus Velten
First Name & Middle Initial & Last Name & Degree
Maria Wittmann
Facility Name
Klinikum Dortmund
City
Dortmund
Country
Germany
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Richard Ellerkmann
First Name & Middle Initial & Last Name & Degree
Holger Pohl
Facility Name
University Hospital Frankfurt
City
Frankfurt
Country
Germany
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Kai Zacharowski
First Name & Middle Initial & Last Name & Degree
Simone Lindau
Facility Name
University Hospital Hamburg
City
Hamburg
Country
Germany
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Lars Eichler
First Name & Middle Initial & Last Name & Degree
Mark Punke
Facility Name
University Hospital Jena
City
Jena
Country
Germany
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Michael Bauer
First Name & Middle Initial & Last Name & Degree
Frank Bloos
Facility Name
University Hospital Schleswig-Holstein
City
Kiel
Country
Germany
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Gunnar Elke
First Name & Middle Initial & Last Name & Degree
Dirk Schädler
Facility Name
University Hospital Mainz
City
Mainz
Country
Germany
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Eva Wittenmeier
First Name & Middle Initial & Last Name & Degree
Michael Schuster
Facility Name
St. Franziskus Hospital Münster
City
Münster
Country
Germany
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Ullrich Göbel
First Name & Middle Initial & Last Name & Degree
Andre Hemping-Bovenkerk
Facility Name
University Hospital Münster
City
Münster
Country
Germany
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Alexander Zarbock
First Name & Middle Initial & Last Name & Degree
Melanie Meersch
Facility Name
University Hospital Regensburg
City
Regensburg
Country
Germany
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Diane Bitzinger
First Name & Middle Initial & Last Name & Degree
Karin Pfister
Facility Name
University Hospital Würzburg
City
Würzburg
ZIP/Postal Code
97080
Country
Germany
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Patrick Meybohm, MD
Phone
004093120130001
Email
meybohm_p@ukw.de
First Name & Middle Initial & Last Name & Degree
Peter Kranke, MD

12. IPD Sharing Statement

Citations:
PubMed Identifier
34932836
Citation
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.
Results Reference
derived
PubMed Identifier
30717805
Citation
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.
Results Reference
derived
Links:
URL
http://www.liberal-trial.de
Description
Related Info

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Liberal Transfusion Strategy in Elderly Patients

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