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Optimal Oxygenation in the Intensive Care Unit (O2-ICU)

Primary Purpose

Systemic Inflammatory Response Syndrome

Status
Completed
Phase
Phase 4
Locations
Netherlands
Study Type
Interventional
Intervention
Oxygen
Sponsored by
Amsterdam UMC, location VUmc
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional supportive care trial for Systemic Inflammatory Response Syndrome focused on measuring oxygen, hypoxia, hyperoxia, critical care, intensive care

Eligibility Criteria

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

Inclusion Criteria:

  • ≥2 positive SIRS-criteria:

    • Temperature >38 deg.C or hypothermia <36 deg.C
    • Heart rate >90 bpm
    • Respiratory rate >20 /min or pCO2 <32 mmHg (4.3 kPa)
    • Number of leucocytes >12 x 10^9/l of <4 x 10^9/l of >10% bands
  • Within 12 hours of admittance to the ICU
  • Expected stay of more than 48 hours as estimated by the attending physician

Exclusion Criteria:

  • Elective surgery
  • Carbon monoxide poisoning
  • Cyanide intoxication
  • Methemoglobinemia
  • Sickle cell anemia
  • Severe pulmonary arterial hypertension (WHO class III or IV)
  • Known severe Acute Respiratory Distress Syndrome (ARDS) (PaO2/FiO2 ≤100 mmHg and PEEP ≥ 5 cm H2O)
  • Known cardiac right to left shunting
  • Pregnancy
  • Severe Chronic Obstructive Pulmonary Disease (COPD) (Gold class III or IV) or other severe chronic pulmonary disease
  • Patients participating in other interventional trials

Sites / Locations

  • VU University Medical Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Active Comparator

Arm Label

High-normal PaO2

Low-normal PaO2

Arm Description

In patients requiring respiratory monitoring, supplemental oxygen is titrated to achieve a PaO2 of 120 mmHg (16 kPa), range 105-135 mmHg (14-18 kPa).

In patients requiring respiratory monitoring, supplemental oxygen is titrated to achieve a target PaO2 of 75 mmHg (10 kPa), range 60-90 mmHg (8-18 kPa).

Outcomes

Primary Outcome Measures

Daily Delta Sequential Organ Failure Assessment Score
The primary endpoint will be cumulative daily delta SOFA score (CDDS) from day 1 to day 14, calculated as the sum of [daily SOFA score minus admission SOFA score] from day 2 to day 14. Daily SOFA score is calculated as the total of maximum scores for each organ system excluding respiratory system (because of possible PaO2/FiO2 distortion). For patients discharged from the ICU, SOFA score will be registered as 0 from the day of discharge to day 14. Death in the ICU will be registered as a score of 20 (maximum) from the day of death to day 14.

Secondary Outcome Measures

total maximum SOFA score minus SOFA score on admission
SOFA rate of decline
Total maximum SOFA score, total maximum SOFA score minus SOFA score on admission, SOFA rate of decline
Mortality
Hypoxic events (PaO2 <55 mmHg)
Vasopressor / Inotrope requirements
Renal function, fluid balance
Oxidative stress (F2-isoprostanes)
Duration of mechanical ventilation and ventilator-free days
Length of stay (ICU)
Length of stay (hospital)
Systemic Vascular Resistance Index
In a random subpopulation.
Cardiac Index
In a random subpopulation.
Microcirculatory flow index and Perfused vessel density
In a random subpopulation. Composite endpoint for two sidestream dark-field microcirculatory measurements.

Full Information

First Posted
December 9, 2014
Last Updated
April 13, 2021
Sponsor
Amsterdam UMC, location VUmc
Collaborators
ZonMw: The Netherlands Organisation for Health Research and Development, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA), Tergooi Hospital
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1. Study Identification

Unique Protocol Identification Number
NCT02321072
Brief Title
Optimal Oxygenation in the Intensive Care Unit
Acronym
O2-ICU
Official Title
The Effects of Hyperoxia on Organ Dysfunction and Outcome in Critically Ill Patients With SIRS
Study Type
Interventional

2. Study Status

Record Verification Date
April 2021
Overall Recruitment Status
Completed
Study Start Date
February 2015 (Actual)
Primary Completion Date
January 2019 (Actual)
Study Completion Date
May 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Amsterdam UMC, location VUmc
Collaborators
ZonMw: The Netherlands Organisation for Health Research and Development, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA), Tergooi Hospital

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
Objectives: To study the short- and long-term effect of two different PaO2 targets on circulatory status, organ dysfunction and outcome in patient admitted to the ICU with Systemic Inflammatory Response Syndrome (SIRS) criteria. To study underlying mechanisms of hyperoxia by determining differences in oxidative stress response between the hyperoxic and the normoxic patients. Study design: Randomized, prospective multicentre clinical trial Study population: Patients admitted to the Intensive Care unit with ≥ 2 positive SIRS-criteria and an expected ICU stay of more than 48 hours Intervention: Group 1: target PaO2 120 (105 - 135) mmHg (high-normal) Group 2: target PaO2 75 (60 - 90) mmHg (low-normal) Primary endpoints: The primary endpoint will be cumulative daily delta SOFA score (CDDS) from day 1 to day 14.
Detailed Description
Rationale: Contrary to hypoxia, many physicians do not consider hyperoxia harmful for their patients. To prevent hypoxia, superfluous administration of oxygen is common practice, and hyperoxia is seen in many patients, especially on Intensive Care units. However, an increasing number of studies not only confirm the known negative pulmonary effects of chronic oxygen oversupply, but also important and more acute circulatory effects, characterised by decreased cardiac output (CO), increased systemic vascular resistance (SVR), and impaired microvascular perfusion. These phenomena can impair perfusion of organs, which may outweigh higher arterial oxygen content, resulting in a net loss of oxygen delivery and perturbed organ function. This may for example be responsible for hyperoxia-associated increased infarct size and increased mortality after myocardial infarction and cardiac arrest. The underlying mechanisms are not clarified yet, but probably involve increased oxidative stress with systemic vasoconstriction. On the other hand, hyperoxia can also induce several favourable effects. The majority of ICU-patients have a systemic inflammatory response syndrome (SIRS) with concomitant vasoplegia due to trauma, sepsis or ischemia/reperfusion injury. Vasoconstriction could benefit these patients with severe SIRS, reducing the need for intravenous volume resuscitation and vasopressor requirements. Furthermore, hyperoxia may exert a preconditioning effect in patients with ischemia/reperfusion injury and prevent new infections due to its antibacterial properties. Hypothesis: Hyperoxia during SIRS ultimately has unfavourable effects on organ function, especially on a longer term. Objectives: To study the short- and long-term effect of two different PaO2 targets on circulatory status, organ dysfunction and outcome. To study underlying mechanisms of hyperoxia by determining differences in oxidative stress response between the hyperoxic and the normoxic patients. Study design: Randomized, prospective multicentre clinical trial Study population: Patients admitted to the Intensive Care unit with ≥ 2 positive SIRS-criteria and an expected ICU stay of more than 48 hours Intervention: We will investigate 2 groups with PaO2 targets both within the range of current practice Group 1: target PaO2 120 (105 - 135) mmHg (high-normal) Group 2: target PaO2 75 (60 - 90) mmHg (low-normal)

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Systemic Inflammatory Response Syndrome
Keywords
oxygen, hypoxia, hyperoxia, critical care, intensive care

7. Study Design

Primary Purpose
Supportive Care
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
400 (Actual)

8. Arms, Groups, and Interventions

Arm Title
High-normal PaO2
Arm Type
Active Comparator
Arm Description
In patients requiring respiratory monitoring, supplemental oxygen is titrated to achieve a PaO2 of 120 mmHg (16 kPa), range 105-135 mmHg (14-18 kPa).
Arm Title
Low-normal PaO2
Arm Type
Active Comparator
Arm Description
In patients requiring respiratory monitoring, supplemental oxygen is titrated to achieve a target PaO2 of 75 mmHg (10 kPa), range 60-90 mmHg (8-18 kPa).
Intervention Type
Drug
Intervention Name(s)
Oxygen
Primary Outcome Measure Information:
Title
Daily Delta Sequential Organ Failure Assessment Score
Description
The primary endpoint will be cumulative daily delta SOFA score (CDDS) from day 1 to day 14, calculated as the sum of [daily SOFA score minus admission SOFA score] from day 2 to day 14. Daily SOFA score is calculated as the total of maximum scores for each organ system excluding respiratory system (because of possible PaO2/FiO2 distortion). For patients discharged from the ICU, SOFA score will be registered as 0 from the day of discharge to day 14. Death in the ICU will be registered as a score of 20 (maximum) from the day of death to day 14.
Time Frame
14 days
Secondary Outcome Measure Information:
Title
total maximum SOFA score minus SOFA score on admission
Time Frame
14 days
Title
SOFA rate of decline
Time Frame
14 days
Title
Total maximum SOFA score, total maximum SOFA score minus SOFA score on admission, SOFA rate of decline
Time Frame
14 days
Title
Mortality
Time Frame
14 days, in-ICU (max 90 days), in-hospital (max 90 days)
Title
Hypoxic events (PaO2 <55 mmHg)
Time Frame
14 days
Title
Vasopressor / Inotrope requirements
Time Frame
14 days
Title
Renal function, fluid balance
Time Frame
14 days
Title
Oxidative stress (F2-isoprostanes)
Time Frame
days 1, 3, 7
Title
Duration of mechanical ventilation and ventilator-free days
Time Frame
14 days
Title
Length of stay (ICU)
Time Frame
average expected 2 to 28 days
Title
Length of stay (hospital)
Time Frame
average expected 10 to 28 days
Title
Systemic Vascular Resistance Index
Description
In a random subpopulation.
Time Frame
14 days
Title
Cardiac Index
Description
In a random subpopulation.
Time Frame
14 days
Title
Microcirculatory flow index and Perfused vessel density
Description
In a random subpopulation. Composite endpoint for two sidestream dark-field microcirculatory measurements.
Time Frame
14 days

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: ≥2 positive SIRS-criteria: Temperature >38 deg.C or hypothermia <36 deg.C Heart rate >90 bpm Respiratory rate >20 /min or pCO2 <32 mmHg (4.3 kPa) Number of leucocytes >12 x 10^9/l of <4 x 10^9/l of >10% bands Within 12 hours of admittance to the ICU Expected stay of more than 48 hours as estimated by the attending physician Exclusion Criteria: Elective surgery Carbon monoxide poisoning Cyanide intoxication Methemoglobinemia Sickle cell anemia Severe pulmonary arterial hypertension (WHO class III or IV) Known severe Acute Respiratory Distress Syndrome (ARDS) (PaO2/FiO2 ≤100 mmHg and PEEP ≥ 5 cm H2O) Known cardiac right to left shunting Pregnancy Severe Chronic Obstructive Pulmonary Disease (COPD) (Gold class III or IV) or other severe chronic pulmonary disease Patients participating in other interventional trials
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
A.M.E. de Man, MD, PhD
Organizational Affiliation
Amsterdam UMC, location VUmc
Official's Role
Principal Investigator
Facility Information:
Facility Name
VU University Medical Center
City
Amsterdam
ZIP/Postal Code
1081 HV
Country
Netherlands

12. IPD Sharing Statement

Citations:
PubMed Identifier
34463696
Citation
Gelissen H, de Grooth HJ, Smulders Y, Wils EJ, de Ruijter W, Vink R, Smit B, Rottgering J, Atmowihardjo L, Girbes A, Elbers P, Tuinman PR, Oudemans-van Straaten H, de Man A. Effect of Low-Normal vs High-Normal Oxygenation Targets on Organ Dysfunction in Critically Ill Patients: A Randomized Clinical Trial. JAMA. 2021 Sep 14;326(10):940-948. doi: 10.1001/jama.2021.13011.
Results Reference
derived

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Optimal Oxygenation in the Intensive Care Unit

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