Clinical trial NCT05029167: REstrictive Versus LIberal Oxygen Strategy and Its Effect on Pulmonary Hypertension After Out-of-hospital Cardiac Arrest (RELIEPH-study)
Official title: REstrictive Versus LIberal Oxygen Strategy and Its Effect on Pulmonary Hypertension After Out-of-hospital Cardiac Arrest (RELIEPH-study): a Substudy Protocol for a Randomised Clinical Trial
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Hypertension, Pulmonary Arterial
Out-Of-Hospital Cardiac Arrest
Intensive Care Unit
Oxygen Therapy
Mechanical Ventilation
Resuscitation
Keywords: Out-of-hospital cardiac arrest
Resuscitation
Oxygen
Intensive Care Unit
Mechanical ventilation
Pulmonary Hypertension
Lead sponsor: University of Southern Denmark
Sponsor class: OTHER
First posted: 2021-08-31
Enrollment: 300
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: The RELIEPH trial is a substudy of the BOX trial, which is a multicenter, randomised clinical trial with a 2x2 factorial design. Patients are allocated 1:1:1:1 to two interventions, respectively high- or low mean arterial pressures (double blinded) and restrictive- or liberal oxygenation (open label). The RELIEPH trial focuses on the oxygen intervention and only has access to data from one trial site. This makes the RELIEPH trial a single-center, parallel-group randomised controlled trial with patients allocated 1:1 to the oxygen target interventions.
Primary purpose: TREATMENT

Brief summary: Background: For patients with out-of-hospital cardiac arrest (OHCA) at the intensive care unit (ICU), oxygen therapy plays an important role in post resuscitation care. During hospitalisation, a lot of these patients occur with pulmonary arterial hypertension (PAH). Currently a wide oxygen target is recommended but no evidence regarding optimal treatment targets to minimise the prevalence of PAH exists.

Methods: The RELIEPH trial is a substudy within the BOX (Blood pressure and OXygenation targets in post resuscitation care) trial. It is a single-center, parallel-group randomised controlled clinical trial. 300 patients with OHCA hospitalised at the ICU are allocated to one of the two oxygenation interventions, either a restrictive- (9-10 kPa) or liberal (13-14 kPa) oxygen target both within the recommended range. The primary outcome is the fraction of time with pulmonary hypertension (mPAP \>25 mmHg) out of total time with mechanical ventilation. Secondary outcomes are: length of ICU stay among survivors, lactate clearance, right ventricular failure, 30 days mortality and plasma brain natriuretic peptide (BNP) level 48 hours from randomisation.

Discussion: This study hypothesises that a liberal target of oxygen reduces the time with PAH during mechanical ventilation compared to a restrictive oxygen target in patients with OHCA at the ICU. When completed, this study hopes to provide new knowledge regarding which oxygen target is beneficial for this group of patients.


Eligibility criteria: Inclusion Criteria:

* Age ≥18 years
* OHCA of presumed cardiac cause
* Sustained ROSC
* Unconsciousness (Glasgow coma scale \<8) after sustained ROSC

Exclusion Criteria:

* Conscious patients (obeying verbal commands)
* Females of childbearing potential (unless a negative HCG test can rule out pregnancy within the inclusion window)
* In-hospital cardiac arrest
* OHCA of presumed non-cardiac cause e.g. after trauma or dissection/rupture of major artery or cardiac arrest caused by initial hypoxia (i.e. drowning, suffocation, hanging).
* Known bleeding diathesis (medically induced coagulopathy (e.g. warfarin, NOAC, clopidogrel) does not exclude the patient)
* Suspected or confirmed acute intracranial bleeding
* Suspected or confirmed acute stroke
* Unwitnessed asystole
* Known limitations in therapy and Do Not Resuscitate-order
* Known disease making 180 days survival unlikely
* Known pre-arrest cerebral performance category 3 or 4
* \>4 hours (240 minutes) from ROSC to screening
* Systolic blood pressure \<80 mmHg in spite of fluid loading/vasopressor and/or inotropic medication/intra-aortic balloon pump/axial flow device
* Temperature on admission \<30°C

Primary outcomes:
measure: Pulmonary hypertension
timeFrame: Up to 30 days.
Secondary outcomes:
measure: Length of ICU stay.
timeFrame: Up to 8 weeks.
measure: Lactate clearance.
timeFrame: 24 hours.
measure: Right ventricular failure.
timeFrame: Up to 8 weeks.
measure: Mortality.
timeFrame: 30 days after ROSC.
measure: Plasma brain natriuretic peptide.
timeFrame: 48 hours from randomisation.
Other outcomes:
Locations:
city: Odense
country: Denmark
facility: Depart med Cardiothoracic Intensive Care, Odense University Hospital
state: Syddanmark
Study officials:
References:
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