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

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ClinicalTrials.gov Identifier: NCT02321072
Recruitment Status : Recruiting
First Posted : December 22, 2014
Last Update Posted : April 26, 2019
Sponsor:
Collaborators:
ZonMw: The Netherlands Organisation for Health Research and Development
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Tergooi Hospital
Information provided by (Responsible Party):
Angelique Spoelstra-de Man, VU University Medical Center

Brief Summary:

Objectives:

  1. 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.
  2. 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.


Condition or disease Intervention/treatment Phase
Systemic Inflammatory Response Syndrome Drug: Oxygen Phase 4

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:

  1. To study the short- and long-term effect of two different PaO2 targets on circulatory status, organ dysfunction and outcome.
  2. 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)

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 385 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Supportive Care
Official Title: The Effects of Hyperoxia on Organ Dysfunction and Outcome in Critically Ill Patients With SIRS
Study Start Date : February 2015
Actual Primary Completion Date : April 2019
Estimated Study Completion Date : December 2019

Arm Intervention/treatment
Active Comparator: High-normal PaO2
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).
Drug: Oxygen
Active Comparator: Low-normal PaO2
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).
Drug: Oxygen



Primary Outcome Measures :
  1. Daily Delta Sequential Organ Failure Assessment Score [ Time Frame: 14 days ]

    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 :
  1. total maximum SOFA score minus SOFA score on admission [ Time Frame: 14 days ]
  2. SOFA rate of decline [ Time Frame: 14 days ]
  3. Total maximum SOFA score, total maximum SOFA score minus SOFA score on admission, SOFA rate of decline [ Time Frame: 14 days ]
  4. Mortality [ Time Frame: 14 days, in-ICU (max 90 days), in-hospital (max 90 days) ]
  5. Hypoxic events (PaO2 <55 mmHg) [ Time Frame: 14 days ]
  6. Vasopressor / Inotrope requirements [ Time Frame: 14 days ]
  7. Renal function, fluid balance [ Time Frame: 14 days ]
  8. Oxidative stress (F2-isoprostanes) [ Time Frame: days 1, 3, 7 ]
  9. Duration of mechanical ventilation and ventilator-free days [ Time Frame: 14 days ]
  10. Length of stay (ICU) [ Time Frame: average expected 2 to 28 days ]
  11. Length of stay (hospital) [ Time Frame: average expected 10 to 28 days ]
  12. Systemic Vascular Resistance Index [ Time Frame: 14 days ]
    In a random subpopulation.

  13. Cardiac Index [ Time Frame: 14 days ]
    In a random subpopulation.

  14. Microcirculatory flow index and Perfused vessel density [ Time Frame: 14 days ]
    In a random subpopulation. Composite endpoint for two sidestream dark-field microcirculatory measurements.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02321072


Contacts
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Contact: H.J.S. de Grooth, MD +31 20 444 4444 h.degrooth@vumc.nl
Contact: A.M.E. Spoelstra-de Man, MD, PhD +31 20 444 4444 am.spoelstra@vumc.nl

Locations
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Netherlands
VU University Medical Center Recruiting
Amsterdam, Netherlands, 1081 HV
Contact: Angelique ME Spoelstra-de Man, MD, PhD       am.spoelstra@vumc.nl   
Sponsors and Collaborators
VU University Medical Center
ZonMw: The Netherlands Organisation for Health Research and Development
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Tergooi Hospital
Investigators
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Principal Investigator: A.M.E. Spoelstra-de Man, MD, PhD VU University Medical Center
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Responsible Party: Angelique Spoelstra-de Man, Consultant Intensivist, VU University Medical Center
ClinicalTrials.gov Identifier: NCT02321072    
Other Study ID Numbers: 2014/459
2014-003468-19 ( EudraCT Number )
First Posted: December 22, 2014    Key Record Dates
Last Update Posted: April 26, 2019
Last Verified: April 2019
Keywords provided by Angelique Spoelstra-de Man, VU University Medical Center:
oxygen
hypoxia
hyperoxia
critical care
intensive care
Additional relevant MeSH terms:
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Systemic Inflammatory Response Syndrome
Inflammation
Pathologic Processes
Shock