Systemic Inflammatory Response SyndromePhase 4O2-ICUNCT02321072
Optimal Oxygenation in the Intensive Care Unit
A Phase 4 study testing Oxygen in people with Systemic Inflammatory Response Syndrome, run by Amsterdam UMC, location VUmc at 1 site in Netherlands.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Systemic Inflammatory Response Syndrome
- What is being tested?
- Oxygen
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 400 participants
- Where
- 1 siteNetherlands
- Study dates
- Feb 2015to May 2019
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- ≥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
Who cannot join
- Elective surgery
- Carbon monoxide poisoning
- Cyanide intoxication
- Methemoglobinemia
- Sickle cell anemia
- Severe pulmonary arterial hypertension (WHO class III or IV)
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- 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
Trial locations and contacts
1 site in 1 country.
About this study
Official title: The Effects of Hyperoxia on Organ Dysfunction and Outcome in Critically Ill Patients With SIRS
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.
Read more
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.
Read the 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)
- Conditions
- Systemic Inflammatory Response Syndrome
- Being tested
- Oxygen
- Keywords
- oxygen, hypoxia, hyperoxia, critical care, intensive care
- Medical subject headings
- Systemic Inflammatory Response Syndrome, Hypoxia, Hyperoxia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
OxygenDrug
| Study group | Role | What they receive |
|---|---|---|
| High-normal PaO2 | Active comparator | 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). Receives: Drug: Oxygen |
| Low-normal PaO2 | Active comparator | 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). Receives: Drug: Oxygen |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 14 days
Secondary outcomes (14)
total maximum SOFA score minus SOFA score on admission
Measured: 14 days
SOFA rate of decline
Measured: 14 days
Total maximum SOFA score, total maximum SOFA score minus SOFA score on admission, SOFA rate of decline
Measured: 14 days
Mortality
Measured: 14 days, in-ICU (max 90 days), in-hospital (max 90 days)
Hypoxic events (PaO2 <55 mmHg)
Measured: 14 days
Vasopressor / Inotrope requirements
Measured: 14 days
Renal function, fluid balance
Measured: 14 days
Oxidative stress (F2-isoprostanes)
Measured: days 1, 3, 7
Duration of mechanical ventilation and ventilator-free days
Measured: 14 days
Length of stay (ICU)
Measured: average expected 2 to 28 days
Length of stay (hospital)
Measured: average expected 10 to 28 days
Systemic Vascular Resistance Index
In a random subpopulation.
Measured: 14 days
Cardiac Index
In a random subpopulation.
Measured: 14 days
Microcirculatory flow index and Perfused vessel density
In a random subpopulation. Composite endpoint for two sidestream dark-field microcirculatory measurements.
Measured: 14 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Dec 2014 (estimated)
- Study startFeb 2015
- Primary completionJan 2019
- Study completionMay 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Systemic Inflammatory Response SyndromeStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Supportive care
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 400 participants (actual)
Sponsor and investigators
- Lead sponsor
- Amsterdam UMC, location VUmc
- Sponsor type
- University, hospital or other
- Collaborators
- ZonMw: The Netherlands Organisation for Health Research and Development, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA), Tergooi Hospital
- Responsible party
- Principal investigator, Angelique Spoelstra-de Man, Amsterdam UMC, location VUmc
- Investigators
- A.M.E. de Man, MD, PhD, Principal investigator, Amsterdam UMC, location VUmc
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02321072
- Sponsor's protocol ID
- 2014/459
- Other IDs
- 2014-003468-19, 2014
- Acronym
- O2-ICU
- Status last verified
- Apr 2021
- First submitted
- 9 Dec 2014
- Last updated
- 19 Apr 2021
- Results posted
- No
- Data monitoring committee
- No
Publications
Klitgaard TL, Schjorring OL, Nielsen FM, Meyhoff CS, Perner A, Wetterslev J, Rasmussen BS, Barbateskovic M. Higher versus lower fractions of inspired oxygen or targets of arterial oxygenation for adults admitted to the intensive care unit. Cochrane Database Syst Rev. 2023 Sep 13;9(9):CD012631. doi: 10.1002/14651858.CD012631.pub3.
PubMed 37700687Gelissen 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.
PubMed 34463696
Study at a glance
From the registry record, last updated by the sponsor on 19 Apr 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effects of Hyperoxia on Organ Dysfunction and Outcome in Critically Ill Patients With SIRS
- ClinicalTrials.gov ID
- NCT02321072
- Acronym / sponsor ID
- O2-ICU / 2014/459
- Conditions
- Systemic Inflammatory Response Syndrome
- Keywords
- oxygen, hypoxia, hyperoxia, critical care, intensive care
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 400 participants (actual)
- Lead sponsor
- Amsterdam UMC, location VUmcUniversity, hospital or other
- Collaborators
- ZonMw: The Netherlands Organisation for Health Research and Development, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA), Tergooi Hospital
- Study start
- Feb 2015 (actual)
- Primary completion
- Jan 2019 (actual)
- Study completion
- May 2019 (actual)
- First posted
- 22 Dec 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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)
Study design
- Primary purpose
- Supportive care
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| High-normal PaO2 | Active comparator | Drug: OxygenIn patients requiring respiratory monitoring, supplemental oxygen is titrated to achieve a PaO2 of 120 mmHg (16 kPa), range 105-135 mmHg (14-18 kPa). |
| Low-normal PaO2 | Active comparator | Drug: OxygenIn 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). |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- ≥2 positive SIRS-criteria:
- Within 12 hours of admittance to the ICU
- Expected stay of more than 48 hours as estimated by the attending physician
Key exclusion criteria (11 listed)
- Elective surgery
- Carbon monoxide poisoning
- Cyanide intoxication
- Methemoglobinemia
- Sickle cell anemia
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Oxygen | Drug | High-normal PaO2, Low-normal PaO2 |
Primary outcome
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.
14 secondary outcomes
total maximum SOFA score minus SOFA score on admission
Time frame: 14 days
SOFA rate of decline
Time frame: 14 days
Total maximum SOFA score, total maximum SOFA score minus SOFA score on admission, SOFA rate of decline
Time frame: 14 days
Mortality
Time frame: 14 days, in-ICU (max 90 days), in-hospital (max 90 days)
Hypoxic events (PaO2 <55 mmHg)
Time frame: 14 days
Vasopressor / Inotrope requirements
Time frame: 14 days
Renal function, fluid balance
Time frame: 14 days
Oxidative stress (F2-isoprostanes)
Time frame: days 1, 3, 7
Duration of mechanical ventilation and ventilator-free days
Time frame: 14 days
Length of stay (ICU)
Time frame: average expected 2 to 28 days
Length of stay (hospital)
Time frame: average expected 10 to 28 days
Systemic Vascular Resistance Index
Time frame: 14 days
Cardiac Index
Time frame: 14 days
Microcirculatory flow index and Perfused vessel density
Time frame: 14 days
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Apr 2021.
- Derived from this study: PubMed 37700687Klitgaard TL, Schjorring OL, Nielsen FM, Meyhoff CS, Perner A, Wetterslev J, Rasmussen BS, Barbateskovic M. Higher versus lower fractions of inspired oxygen or targets of arterial oxygenation for adults admitted to the intensive care unit. Cochrane Database Syst Rev. 2023 Sep 13;9(9):CD012631. doi: 10.1002/14651858.CD012631.pub3.
- Derived from this study: PubMed 34463696Gelissen 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
A.M.E. de Man, MD, PhD principal investigator
Amsterdam UMC, location VUmc
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Oxygen in people with Systemic Inflammatory Response Syndrome, run by Amsterdam UMC, location VUmc at 1 site in Netherlands.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 19 Apr 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Daily Delta Sequential Organ Failure Assessment Score (time frame: 14 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02321072, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Apr 2021; AzTrials last refreshed its copy on 30 Oct 2026.