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

Mechanical Ventilation Clinical Trial

— RELIEPH  

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05029167
• Other study ID #: S-2021xxxx
• Status: Recruiting
• Phase: N/A
• Start date: September 11, 2017
• Est. completion date: December 2023

Study information

• Verified date: May 2022
• Source: University of Southern Denmark
• Contact: Mie Mørkøre, MS
• Phone: +45 28555083
• Email: mie.moerk[@]outlook.dk
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 300
• Est. completion date: December 2023
• Est. primary completion date: September 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Heart Arrest
• Hypertension
• Hypertension, Pulmonary
• Hypertension, Pulmonary Arterial
• Intensive Care Unit
• Mechanical Ventilation
• Out-Of-Hospital Cardiac Arrest
• Oxygen Therapy
• Pulmonary Arterial Hypertension
• Resuscitation

Intervention

Other:
• Restrictive PaO2
Patients are randomized to a PaO2 target of 9-10 kPa (open-label).
• Low normal MAP
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.
• Liberal PaO2
Patients are randomized to a PaO2 target of 13-14 kPa (open-label).
• High normal MAP
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.

Locations

Country	Name	City	State
Denmark	Depart med Cardiothoracic Intensive Care, Odense University Hospital	Odense	Syddanmark

Sponsors (1)

Lead Sponsor	Collaborator
University of Southern Denmark

Country where clinical trial is conducted

Denmark, 

References & Publications (19)

Asfar P, Schortgen F, Boisramé-Helms J, Charpentier J, Guérot E, Megarbane B, Grimaldi D, Grelon F, Anguel N, Lasocki S, Henry-Lagarrigue M, Gonzalez F, Legay F, Guitton C, Schenck M, Doise JM, Devaquet J, Van Der Linden T, Chatellier D, Rigaud JP, Dellamonica J, Tamion F, Meziani F, Mercat A, Dreyfuss D, Seegers V, Radermacher P; HYPER2S Investigators; REVA research network. Hyperoxia and hypertonic saline in patients with septic shock (HYPERS2S): a two-by-two factorial, multicentre, randomised, clinical trial. Lancet Respir Med. 2017 Mar;5(3):180-190. doi: 10.1016/S2213-2600(17)30046-2. Epub 2017 Feb 15. Erratum in: Lancet Respir Med. 2017 Aug;5(8):e28. — View Citation

de Jonge E, Peelen L, Keijzers PJ, Joore H, de Lange D, van der Voort PH, Bosman RJ, de Waal RA, Wesselink R, de Keizer NF. Association between administered oxygen, arterial partial oxygen pressure and mortality in mechanically ventilated intensive care unit patients. Crit Care. 2008;12(6):R156. doi: 10.1186/cc7150. Epub 2008 Dec 10. — View Citation

Girardis M, Busani S, Damiani E, Donati A, Rinaldi L, Marudi A, Morelli A, Antonelli M, Singer M. Effect of Conservative vs Conventional Oxygen Therapy on Mortality Among Patients in an Intensive Care Unit: The Oxygen-ICU Randomized Clinical Trial. JAMA. 2016 Oct 18;316(15):1583-1589. doi: 10.1001/jama.2016.11993. — View Citation

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Huynh TN, Weigt SS, Sugar CA, Shapiro S, Kleerup EC. Prognostic factors and outcomes of patients with pulmonary hypertension admitted to the intensive care unit. J Crit Care. 2012 Dec;27(6):739.e7-13. doi: 10.1016/j.jcrc.2012.08.006. Epub 2012 Oct 22. — View Citation

Kirkegaard H, Taccone FS, Skrifvars M, Søreide E. Postresuscitation Care after Out-of-hospital Cardiac Arrest: Clinical Update and Focus on Targeted Temperature Management. Anesthesiology. 2019 Jul;131(1):186-208. doi: 10.1097/ALN.0000000000002700. Review. — View Citation

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Panwar R, Hardie M, Bellomo R, Barrot L, Eastwood GM, Young PJ, Capellier G, Harrigan PW, Bailey M; CLOSE Study Investigators; ANZICS Clinical Trials Group. Conservative versus Liberal Oxygenation Targets for Mechanically Ventilated Patients. A Pilot Multicenter Randomized Controlled Trial. Am J Respir Crit Care Med. 2016 Jan 1;193(1):43-51. doi: 10.1164/rccm.201505-1019OC. — View Citation

Schjørring OL, Klitgaard TL, Perner A, Wetterslev J, Lange T, Siegemund M, Bäcklund M, Keus F, Laake JH, Morgan M, Thormar KM, Rosborg SA, Bisgaard J, Erntgaard AES, Lynnerup AH, Pedersen RL, Crescioli E, Gielstrup TC, Behzadi MT, Poulsen LM, Estrup S, Laigaard JP, Andersen C, Mortensen CB, Brand BA, White J, Jarnvig IL, Møller MH, Quist L, Bestle MH, Schønemann-Lund M, Kamper MK, Hindborg M, Hollinger A, Gebhard CE, Zellweger N, Meyhoff CS, Hjort M, Bech LK, Grøfte T, Bundgaard H, Østergaard LHM, Thyø MA, Hildebrandt T, Uslu B, Sølling CG, Møller-Nielsen N, Brøchner AC, Borup M, Okkonen M, Dieperink W, Pedersen UG, Andreasen AS, Buus L, Aslam TN, Winding RR, Schefold JC, Thorup SB, Iversen SA, Engstrøm J, Kjær MN, Rasmussen BS; HOT-ICU Investigators. Lower or Higher Oxygenation Targets for Acute Hypoxemic Respiratory Failure. N Engl J Med. 2021 Apr 8;384(14):1301-1311. doi: 10.1056/NEJMoa2032510. Epub 2021 Jan 20. — View Citation

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Zhang Z, Xu X. Lactate clearance is a useful biomarker for the prediction of all-cause mortality in critically ill patients: a systematic review and meta-analysis*. Crit Care Med. 2014 Sep;42(9):2118-25. doi: 10.1097/CCM.0000000000000405. Review. — View Citation

* Note: There are 19 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Pulmonary hypertension	Fraction of time with pulmonary hypertension (mPAP >25 mmHg) out of total time with mechanical ventilation.	Up to 30 days.
Secondary	Length of ICU stay.	Length of ICU stay among survivors.	Up to 8 weeks.
Secondary	Lactate clearance.	>30% reduction in lactate level.	24 hours.
Secondary	Right ventricular failure.	Cardiac index <2 and central venous pressure >18 mmHg.	Up to 8 weeks.
Secondary	Mortality.	Dead or alive.	30 days after ROSC.
Secondary	Plasma brain natriuretic peptide.	Plasma brain natriuretic peptide level.	48 hours from randomisation.

External Links

•   Blood Pressure and OXygenation Targets After OHCA