Insufficient Cellular Oxygen in ICU Patients With Anaemia (INOX ICU-2)

Insufficient Cellular Oxygen in ICU Patients With Anaemia: the INOX ICU-2 Study

The purpose of this study is whether the mitochondrial oxygenation tension (mitoPO2) is a feasible and reliable tool in ICU patients with anaemia undergoing red cell transfusion to ultimately personalize blood transfusion decisions in the ICU.

Study Overview

• Status: Terminated
• Conditions: Anemia; Critical Care; Erythrocyte Transfusion; Oxygen; Mitochondria

Detailed Description

Evidence is increasing that in some cases a Hb trigger of 7-8g/dl may be too low and te question arises whether an individualized red cell transfusion strategy may benefit critically ill patients. New studies have shown the potential of protoporphyrin IX-triple state lifetime technique to measure mitochondrial oxygenation tension (mitoPO2) in vivo, which possibly is an early indicator of oxygen disturbance in the cell and therefore a physiological trigger for red cell transfusion. The goals are: 1. Determining the feasibility of using mitoPO2 and the variability of mitoPO2 measurements in critically ill intensive care unit (ICU) patients before and after receiving a red cell transfusion 2. Describing the effects of red cell transfusion and the associated change in [Hb] on mitoPO2 and on other physiologic measures of tissue oxygenation and oxygen balance 3. Describing the association between mitoPO2 and vital organ functions. Included patients will undergo red cell transfusion as planned. However, red cell transfusion will be delayed by 2 hours. At multiple predefined moments data collection including blood samples and measurements of mitoPO2 will take place.

The results of this study cannot be immediately translated to clinical practice. Using these results, the investigators will design a phase 2 diagnostic study, most probably a randomized clinical trial that will yield applied knowledge with respect to personalizing red cell transfusion. Application will be in ICU patients with anaemia who might or might not profit from red cell transfusions. It will lead to a reduction of both over- and under- transfusion.

• Study Type: Observational
• Enrollment (Actual): 103

Contacts and Locations

Study Locations

• Netherlands
  • Amsterdam-Zuidoost, Noord-Holland
    • Amsterdam, Amsterdam-Zuidoost, Noord-Holland, Netherlands, 1105 AZ
      • Amsterdam Medical Center
  • Zuid-Holland
    • Leiden, Zuid-Holland, Netherlands, 2333 ZA
      • Leiden University Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

All adult patients admitted to the intensive care unit with a Hb below 6.3 mmol/l, with a central venous catheter in situ, who are planned to undergo a transfusion of red blood cells

Description

Inclusion Criteria:

• adult patient admitted to the ICU
• Hb below 6.3 mmol/l (10 g/dl)
• central venous catheter in situ
• red cell transfusion planned

Exclusion Criteria:

• adults without a legal representative to ask for informed consent
• patients less than 18 years old
• pregnant or breast feeding women
• patients in need of emergency red cell transfusion e.g. bleeding
• not having a central venous catheter in situ
• porphyria and or known photodermatosis
• patients with an expected ICU stay <24 hours
• patients with hypersensitivity to the active substance or to the plaster material of ALA

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
ICU patients with anaemia; At admission to the ICU all patients, or their legal representatives, expected to stay at the ICU for longer than 24 hours will be asked to participate in the study and will be asked informed consent. ICU patients with anaemia in whom a central venous catheter is already in place and in whom a red cell transfusion is planned, will be included in the study.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Variability of mitoPO2	Variability of mitoPO2 before and after red cell transfusion. This will be compared to traditional parameters used to measure oxygenation and oxygen balance.	Variability of mitoPO2 will be assessed during 8 predefined moments (within a timeframe of 24 hours) in the study

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Organ damage	Value of mitoPO2 measurements for predicting (ischemic) organ damage	Value of mitoPO2 in predicting (ischemic) organ damage will be assessed during 8 predefined moments (within a timeframe of 24 hours) in the study
Microcirculation	Association of mitoPO2 with the microcirculation	Association of the mitoPO2 with the microcirculation will be assessed during 2 predefined moments (before transfusion and 24 hours after transfusion) in the study
Length of stay	Length of hospital-stay and ICu stay	Length of stay will be assessed during the 3 months follow-up time
Mortality	90-day mortality, hospital mortality and ICU mortality	Mortality will be assessed during the 3 months follow-up time
Adverse events	Adverse and serious adverse events of the mitoPO2 measurements	Association of the mitoPO2 with adverse events will be assessed during 8 predefined moments (within a timeframe of 24 hours) in the study

Collaborators and Investigators

• Sponsor: Sanquin-LUMC J.J van Rood Center for Clinical Transfusion Research
• Collaborators: Erasmus Medical Center; Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA); Leiden University Medical Center
• Investigators: Study Chair: Johanna G van der Bom, PhD, MD, Leiden University Medical Center and Sanquin Research Leiden; Study Chair: M S Arbous, PhD, MD, Leiden University Medical Center; Principal Investigator: M Baysan, MD, Leiden University Medical Center and Sanquin Research Leiden

Publications and helpful links

General Publications

• Baysan M, Arbous MS, Mik EG, Juffermans NP, van der Bom JG. Study protocol and pilot results of an observational cohort study evaluating effect of red blood cell transfusion on oxygenation and mitochondrial oxygen tension in critically ill patients with anaemia: the INsufficient Oxygenation in the Intensive Care Unit (INOX ICU-2) study. BMJ Open. 2020 May 17;10(5):e036351. doi: 10.1136/bmjopen-2019-036351.

Study record dates

Study Major Dates

• Study Start (Actual): May 16, 2017
• Primary Completion (Actual): July 1, 2021
• Study Completion (Actual): December 1, 2022

Study Registration Dates

• First Submitted: March 13, 2017
• First Submitted That Met QC Criteria: March 20, 2017
• First Posted (Actual): March 27, 2017

Study Record Updates

• Last Update Posted (Estimate): January 19, 2023
• Last Update Submitted That Met QC Criteria: January 17, 2023
• Last Verified: December 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Hematologic Diseases; Anemia
• Other Study ID Numbers: NL59512.058.16

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided
• IPD Plan Description: to be decided