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

NCT05029167 | Unknown DMC

• 1 other identifier: S-2021xxxx
• Study Type: interventional
• Target: 300
• Locations: 1 country
• Sites: 1

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.

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

Outcome Measures

Primary Outcomes (1)

• Pulmonary hypertension

  Fraction of time with pulmonary hypertension (mPAP \>25 mmHg) out of total time with mechanical ventilation.

  Up to 30 days.

Secondary Outcomes (5)

• Length of ICU stay.

  Up to 8 weeks.

• Lactate clearance.

  24 hours.

• Right ventricular failure.

  Up to 8 weeks.

• Mortality.

  30 days after ROSC.

• Plasma brain natriuretic peptide.

  48 hours from randomisation.

Study Arms (4)

Restrictive PaO2 and low normal MAP

ACTIVE COMPARATOR

Patients receiving PaO2 9-10 kPa (68-75 mmHg) and MAP 63 mmHg during targeted temperature management (36 hours) after OHCA.

Other: Restrictive PaO2; Other: Low normal MAP

Restrictive PaO2 and high normal MAP

ACTIVE COMPARATOR

Patients receiving PaO2 9-10 kPa (68-75 mmHg) and MAP 77 mmHg during targeted temperature management (36 hours) after OHCA.

Other: Restrictive PaO2; Other: High normal MAP

Liberal PaO2 and low normal MAP

ACTIVE COMPARATOR

Patients receiving PaO2 13-14 kPa (98-105 mmHg) and MAP 63 mmHg during targeted temperature management (36 hours) after OHCA.

Other: Low normal MAP; Other: Liberal PaO2

Liberal PaO2 and high normal MAP

ACTIVE COMPARATOR

Patients receiving PaO2 13-14 kPa (98-105 mmHg) and MAP 77 mmHg during targeted temperature management (36 hours) after OHCA.

Other: Liberal PaO2; Other: High normal MAP

Interventions

Restrictive PaO2 OTHER

Patients are randomized to a PaO2 target of 9-10 kPa (open-label).

Also known as: PaO2 target at 9-10 kPa.

Restrictive PaO2 and high normal MAP; Restrictive PaO2 and low normal MAP

Low normal MAP OTHER

The patients are randomized to receive a Phillips M1006B blood pressure measuring module, offset by +10 %. All patients will target a MAP of 70, but due to the offset module, the patients will target an actual blood pressure of 63 mmHg.

Also known as: Mean arterial blood pressure at 63 mmHg.

Liberal PaO2 and low normal MAP; Restrictive PaO2 and low normal MAP

Liberal PaO2 OTHER

Patients are randomized to a PaO2 target of 13-14 kPa (open-label).

Also known as: PaO2 target at 13-14 kPa.

Liberal PaO2 and high normal MAP; Liberal PaO2 and low normal MAP

High normal MAP OTHER

The patients are randomized to receive a Phillips M1006B blood pressure measuring module, offset by -10 %. All patients will target a MAP of 70, but due to the offset module, the patients will target an actual blood pressure of 77mmHg.

Also known as: Mean arterial blood pressure at 77 mmHg.

Liberal PaO2 and high normal MAP; Restrictive PaO2 and high normal MAP

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• Conscious patients (obeying verbal commands)
• 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

Sponsors & Collaborators

• University of Southern Denmark: lead

Study Sites (1)

Depart med Cardiothoracic Intensive Care, Odense University Hospital

Odense, Region Syddanmark, 5000, Denmark

RECRUITING

Related Publications (19)

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Related Links

• Blood Pressure and OXygenation Targets After OHCA

MeSH Terms

Conditions

Pulmonary Arterial Hypertension; Out-of-Hospital Cardiac Arrest; Hypertension, Pulmonary

Condition Hierarchy (Ancestors)

Lung Diseases; Respiratory Tract Diseases; Heart Arrest; Heart Diseases; Cardiovascular Diseases; Hypertension; Vascular Diseases

Central Study Contacts

Mie Mørkøre, MS

CONTACT

+45 28555083; mie.moerk@outlook.dk

Rikke Ingerslev Stage, MS

CONTACT

+45 28569220; rikke.i.stage@gmail.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: August 11, 2021
• First Posted: August 31, 2021
• Study Start: September 11, 2017
• Primary Completion: September 1, 2023
• Study Completion: December 1, 2023
• Last Updated: June 1, 2022

Record last verified: 2022-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ICF
• Time Frame: Data requests can be submitted starting 9 months after article publication and the data will be made accessible for up to 24 months. Extensions will be considered on a case-by-case basis.
• Access Criteria: Access to trial IPD can be requested by qualified researchers engaging in independent scientific research, and will be provided following review and approval of a research proposal and Statistical Analysis Plan and execution of a Data Sharing Agreement.

Locations

DK (1)