REstrictive Versus LIberal Oxygen Strategy and Its Effect on Pulmonary Hypertension After Out-of-hospital Cardiac Arrest (RELIEPH-study)

Not Applicable

• Conditions: Hypertension, Pulmonary Arterial; Out-Of-Hospital Cardiac Arrest; Mechanical Ventilation; Intensive Care Unit; Oxygen Therapy; Resuscitation
• Interventions: Other: Restrictive PaO2; Other: Low normal MAP; Other: Liberal PaO2; Other: High normal MAP

• Registration Number: NCT05029167
• Lead Sponsor: University of Southern Denmark

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2017-09-11
• Study First Submitted: 2021-08-11
• Study First Submitted QC: 2021-08-25
• Study First Posted: 2021-08-31
• Status Verified: 2022-05
• Last Update Submitted: 2022-05-31
• Last Update Posted: 2022-06-01
• Primary Completion: 2023-09
• Study Completion: 2023-12

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 300

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Restrictive PaO2 and low normal MAP	Restrictive PaO2	Patients receiving PaO2 9-10 kPa (68-75 mmHg) and MAP 63 mmHg during targeted temperature management (36 hours) after OHCA.
Liberal PaO2 and low normal MAP	Low normal MAP	Patients receiving PaO2 13-14 kPa (98-105 mmHg) and MAP 63 mmHg during targeted temperature management (36 hours) after OHCA.
Liberal PaO2 and high normal MAP	Liberal PaO2	Patients receiving PaO2 13-14 kPa (98-105 mmHg) and MAP 77 mmHg during targeted temperature management (36 hours) after OHCA.
Restrictive PaO2 and high normal MAP	High normal MAP	Patients receiving PaO2 9-10 kPa (68-75 mmHg) and MAP 77 mmHg during targeted temperature management (36 hours) after OHCA.
Restrictive PaO2 and high normal MAP	Restrictive PaO2	Patients receiving PaO2 9-10 kPa (68-75 mmHg) and MAP 77 mmHg during targeted temperature management (36 hours) after OHCA.
Liberal PaO2 and low normal MAP	Liberal PaO2	Patients receiving PaO2 13-14 kPa (98-105 mmHg) and MAP 63 mmHg during targeted temperature management (36 hours) after OHCA.
Restrictive PaO2 and low normal MAP	Low normal MAP	Patients receiving PaO2 9-10 kPa (68-75 mmHg) and MAP 63 mmHg during targeted temperature management (36 hours) after OHCA.
Liberal PaO2 and high normal MAP	High normal MAP	Patients receiving PaO2 13-14 kPa (98-105 mmHg) and MAP 77 mmHg during targeted temperature management (36 hours) after OHCA.

Primary Outcome Measures

Name	Time	Method
Pulmonary hypertension	Up to 30 days.	Fraction of time with pulmonary hypertension (mPAP \>25 mmHg) out of total time with mechanical ventilation.

Secondary Outcome Measures

Name	Time	Method
Right ventricular failure.	Up to 8 weeks.	Cardiac index \<2 and central venous pressure \>18 mmHg.
Mortality.	30 days after ROSC.	Dead or alive.
Plasma brain natriuretic peptide.	48 hours from randomisation.	Plasma brain natriuretic peptide level.
Length of ICU stay.	Up to 8 weeks.	Length of ICU stay among survivors.
Lactate clearance.	24 hours.	\>30% reduction in lactate level.

Trial Locations

Locations (1)

Depart med Cardiothoracic Intensive Care, Odense University Hospital; 🇩🇰 Odense, Syddanmark, Denmark