Blood Pressure and OXygenation Targets After OHCA

NCT03141099 | Completed DMC

• 1 other identifier: H-16033436
• Study Type: interventional
• Target: 802
• Locations: 1 country
• Sites: 2

Brief Summary

This study compares two blood pressure targets and two oxygenation targets in the post-resuscitation care of comatose out-of-hospital cardiac arrets patients. Using a novel method the blood pressure-intervention is double-blinded. The oxygenation-intervention is open-label. As a subordinate study, the patients will be randomized 1:1 to active fever-control with an automated feedback temperature control-device for 36 or 72 hours following return of spontaneous circulation.

Conditions

Out-of-Hospital Cardiac Arrest; Blood Pressure; Hemodynamic Instability

Keywords

OHCA; Hemodynamic; TTM; post-rescusitation care; Blood pressure targets; Oxygenation targets

Outcome Measures

Primary Outcomes (1)

• All-cause mortality or severe anoxic brain injury

  Death from any cause or discharge from hospital in Cerebral Performance Category 3 or 4

  3 months after OHCA.

Secondary Outcomes (10)

• Renal replacement therapy

  3 months

• Time to death

  180 days

• Neuron-Specific Enolase

  48 hours

• MOCA-score

  3 months

• Modified Ranking Scale

  3 months

Other Outcomes (2)

• Vital status at 180 days post cardiac arrest

  180 days post cardiac arrest

• CPC category at 180 days post cardiac arrest

  180 days post cardiac arrest

Study Arms (4)

Low normal MAP and low normal PaO2

ACTIVE COMPARATOR

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

Other: Low normal MAP; Other: Low normal PaO2.

High normal MAP and low normal PaO2

ACTIVE COMPARATOR

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

Other: High normal MAP; Other: Low normal PaO2.

Low normal MAP and high normal PaO2

ACTIVE COMPARATOR

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

Other: Low normal MAP; Other: High normal PaO2

High normal MAP and high normal PaO2

ACTIVE COMPARATOR

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

Other: High normal MAP; Other: Low normal PaO2.

Interventions

Low normal MAP OTHER

The patients are randomized to recieve 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.

Low normal MAP and high normal PaO2; Low normal MAP and low normal PaO2

High normal MAP OTHER

The patients are randomized to recieve 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 .

High normal MAP and high normal PaO2; High normal MAP and low normal PaO2

Low normal PaO2. OTHER

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

Also known as: PaO2 at 9-10 kPa.

High normal MAP and high normal PaO2; High normal MAP and low normal PaO2; Low normal MAP and low normal PaO2

High normal PaO2 OTHER

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

Also known as: PaO2 at 13-14 kPa.

Low normal MAP and high normal PaO2

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 (GCS \<8) (patients not able to obey verbal commands) after sustained ROSC

You may not qualify if:

• Conscious patients (obeying verbal commands)
• In-hospital cardiac arrest (IHCA)
• 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 CPC 3 or 4
• \>4 hours (240 minutes) from ROSC to screening
• Systolic blood pressure \<80 mm Hg in spite of fluid loading/vasopressor and/or inotropic medication/intra-aortic balloon pump/axial flow device
• Temperature on admission \<30°C.

Sponsors & Collaborators

• Jesper Kjaergaard: lead
• Odense University Hospital: collaborator

Study Sites (2)

Department of Cardiology, Copenhagen University Hospital, Rigshospitalet

Copenhagen, København Ø, 2100, Denmark

Location

Depart med Cardiothoracic Intensive Care, Odense University Hospital

Odense, 5000, Denmark

Location

Related Publications (15)

• Meyer MAS, Beske RP, Molstrom S, Grand J, Obling LER, Wiberg S, Borregaard B, Schneekloth S, Kaad SG, Christensen PM, Christoffersen C, Frikke-Schmidt R, Schmidt H, Moller JE, Kjaergaard J, Hassager C. Neurofilament light chain for prognostication after cardiac arrest-first steps towards validation. Crit Care. 2025 Aug 6;29(1):348. doi: 10.1186/s13054-025-05579-1.

  PMID: 40770665 DERIVED

• Linde L, Beske RP, Meyer MAS, Molstrom S, Grand J, Helgestad OKL, Ravn HB, Schmidt H, Kjaergaard J, Hassager C, Moller JE. Hemodynamic Characteristics and Prognostic Implication of Modified Society for Cardiovascular Angiography and Interventions Shock Classification in Comatose Patients With Out-of-Hospital Cardiac Arrest. J Am Heart Assoc. 2025 Jan 7;14(1):e036659. doi: 10.1161/JAHA.124.036659. Epub 2024 Dec 20.

  PMID: 39704227 DERIVED

• Grand J, Granholm A, Wiberg S, Schmidt H, Moller JE, Molstrom S, Meyer MAS, Josiassen J, Beske RP, Dahl JS, Obling LER, Frydland M, Borregaard B, Lind Jorgensen V, Hartvig Thomsen J, Aalbaek Madsen S, Nyholm B, Hassager C, Kjaergaard J. Lower vs. higher blood pressure targets during intensive care of comatose patients resuscitated from out-of-hospital cardiac arrest-a Bayesian analysis of the BOX trial. Eur Heart J Acute Cardiovasc Care. 2025 Jan 31;14(1):14-23. doi: 10.1093/ehjacc/zuae142.

  PMID: 39658315 DERIVED

• Nyholm B, Grand J, Obling LER, Hassager C, Moller JE, Schmidt H, Othman MH, Kondziella D, Horn J, Kjaergaard J. Validating quantitative pupillometry thresholds for neuroprognostication after out-of-hospital cardiac arrest. A predefined substudy of the Blood Pressure and Oxygenations Targets After Cardiac Arrest (BOX)-trial. Intensive Care Med. 2024 Sep;50(9):1484-1495. doi: 10.1007/s00134-024-07574-6. Epub 2024 Aug 20.

  PMID: 39162825 DERIVED

• Grand J, Hassager C, Schmidt H, Molstrom S, Nyholm B, Obling LER, Meyer MAS, Illum E, Josiassen J, Beske RP, Hoigaard Frederiksen H, Dahl JS, Moller JE, Kjaergaard J. Impact of Blood Pressure Targets in Patients With Heart Failure Undergoing Postresuscitation Care: A Subgroup Analysis From a Randomized Controlled Trial. Circ Heart Fail. 2024 Jun;17(6):e011437. doi: 10.1161/CIRCHEARTFAILURE.123.011437. Epub 2024 Jun 7.

  PMID: 38847097 DERIVED

• Jeppesen KK, Rasmussen SB, Kjaergaard J, Schmidt H, Molstrom S, Beske RP, Grand J, Ravn HB, Winther-Jensen M, Meyer MAS, Hassager C, Moller JE. Acute kidney injury after out-of-hospital cardiac arrest. Crit Care. 2024 May 18;28(1):169. doi: 10.1186/s13054-024-04936-w.

  PMID: 38762578 DERIVED

• Meyer MAS, Hassager C, Molstrom S, Borregaard B, Grand J, Nyholm B, Obling LER, Beske RP, Meyer ASP, Bekker-Jensen D, Winther-Jensen M, Jorgensen VL, Schmidt H, Moller JE, Kjaergaard J. Combined effects of targeted blood pressure, oxygenation, and duration of device-based fever prevention after out-of-hospital cardiac arrest on 1-year survival: post hoc analysis of a randomized controlled trial. Crit Care. 2024 Jan 12;28(1):20. doi: 10.1186/s13054-023-04794-y.

  PMID: 38216985 DERIVED

• Grand J, Hassager C, Schmidt H, Molstrom S, Nyholm B, Hoigaard HF, Dahl JS, Meyer M, Beske RP, Obling L, Kjaergaard J, Moller JE. Serial assessments of cardiac output and mixed venous oxygen saturation in comatose patients after out-of-hospital cardiac arrest. Crit Care. 2023 Oct 27;27(1):410. doi: 10.1186/s13054-023-04704-2.

  PMID: 37891623 DERIVED

• Rasmussen SB, Jeppesen KK, Kjaergaard J, Hassager C, Schmidt H, Molstrom S, Beske RP, Grand J, Ravn HB, Winther-Jensen M, Meyer MAS, Moller JE. Blood Pressure and Oxygen Targets on Kidney Injury After Cardiac Arrest. Circulation. 2023 Dec 5;148(23):1860-1869. doi: 10.1161/CIRCULATIONAHA.123.066012. Epub 2023 Oct 4.

  PMID: 37791480 DERIVED

• Nyholm B, Grand J, Obling LER, Hassager C, Moller JE, Schmidt H, Othman MH, Kondziella D, Kjaergaard J. Quantitative pupillometry for neuroprognostication in comatose post-cardiac arrest patients: A protocol for a predefined sub-study of the Blood pressure and Oxygenations Targets after Out-of-Hospital Cardiac Arrest (BOX)-trial. Resusc Plus. 2023 Sep 26;16:100475. doi: 10.1016/j.resplu.2023.100475. eCollection 2023 Dec.

  PMID: 37779885 DERIVED

• Hassager C, Schmidt H, Moller JE, Grand J, Molstrom S, Beske RP, Boesgaard S, Borregaard B, Bekker-Jensen D, Dahl JS, Frydland MS, Hofsten DE, Isse YA, Josiassen J, Lind Jorgensen VR, Kondziella D, Lindholm MG, Moser E, Nyholm BC, Obling LER, Sarkisian L, Sondergaard FT, Thomsen JH, Thune JJ, Veno S, Wiberg SC, Winther-Jensen M, Meyer MAS, Kjaergaard J. Duration of Device-Based Fever Prevention after Cardiac Arrest. N Engl J Med. 2023 Mar 9;388(10):888-897. doi: 10.1056/NEJMoa2212528. Epub 2022 Nov 6.

  PMID: 36342119 DERIVED

• Schmidt H, Kjaergaard J, Hassager C, Molstrom S, Grand J, Borregaard B, Roelsgaard Obling LE, Veno S, Sarkisian L, Mamaev D, Jensen LO, Nyholm B, Hofsten DE, Josiassen J, Thomsen JH, Thune JJ, Lindholm MG, Stengaard Meyer MA, Winther-Jensen M, Sorensen M, Frydland M, Beske RP, Frikke-Schmidt R, Wiberg S, Boesgaard S, Lind Jorgensen V, Moller JE. Oxygen Targets in Comatose Survivors of Cardiac Arrest. N Engl J Med. 2022 Oct 20;387(16):1467-1476. doi: 10.1056/NEJMoa2208686. Epub 2022 Aug 27.

  PMID: 36027567 DERIVED

• Kjaergaard J, Moller JE, Schmidt H, Grand J, Molstrom S, Borregaard B, Veno S, Sarkisian L, Mamaev D, Jensen LO, Nyholm B, Hofsten DE, Josiassen J, Thomsen JH, Thune JJ, Obling LER, Lindholm MG, Frydland M, Meyer MAS, Winther-Jensen M, Beske RP, Frikke-Schmidt R, Wiberg S, Boesgaard S, Madsen SA, Jorgensen VL, Hassager C. Blood-Pressure Targets in Comatose Survivors of Cardiac Arrest. N Engl J Med. 2022 Oct 20;387(16):1456-1466. doi: 10.1056/NEJMoa2208687. Epub 2022 Aug 27.

  PMID: 36027564 DERIVED

• Kjaergaard J, Schmidt H, Moller JE, Hassager C. The "Blood pressure and oxygenation targets in post resuscitation care, a randomized clinical trial": design and statistical analysis plan. Trials. 2022 Feb 24;23(1):177. doi: 10.1186/s13063-022-06101-6.

  PMID: 35209951 DERIVED

• Grand J, Hassager C, Schmidt H, Moller JE, Molstrom S, Nyholm B, Kjaergaard J. Hemodynamic evaluation by serial right heart catheterizations after cardiac arrest; protocol of a sub-study from the Blood Pressure and Oxygenation Targets after Out-of-Hospital Cardiac Arrest-trial (BOX). Resusc Plus. 2021 Dec 10;8:100188. doi: 10.1016/j.resplu.2021.100188. eCollection 2021 Dec.

  PMID: 34950913 DERIVED

MeSH Terms

Conditions

Out-of-Hospital Cardiac Arrest

Condition Hierarchy (Ancestors)

Heart Arrest; Heart Diseases; Cardiovascular Diseases

Study Officials

• Jesper Kjaergaard, Md, DMSc

  Rigshospitalet, Denmark

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Target blood pressure will be blinded by offsetting the blood pressure measurering module. The oxygenation- and fever control interventions will be open label. Further life-sustaining treatment will be delivered according to standard procedures and withdrawal of active intensive care will be at the discretion of the treating physicians, but must be delayed for at least 108 hours post ROSC. The steering group and the management group will be blinded to the type of intervention during the entire trial period, when handling the trial database. Follow-up at 30 days (phone call) and 90 days (meeting) will be performed by personnel unaware of the allocation group, treatment complications at the ICU, if they occurred or specialized neurological rehabilitation.
• Purpose: TREATMENT
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: MD, Ph.d., DMSc.

Model Details: Multicenter, randomized trial in 2\*2 factorial design allocating comatose OHCA patients to one of two target blood pressures (double blind) and restrictive vs. liberal oxygenation (open label) during ICU stay with blinded outcome evaluation. Sample size: 800 patients. Patient will be allocated 1:1; for all interventions, no interaction with regards to outcome is expected.

Study Record Dates

• First Submitted: April 30, 2017
• First Posted: May 4, 2017
• Study Start: March 10, 2017
• Primary Completion: December 15, 2021
• Study Completion: March 15, 2022
• Last Updated: June 30, 2022

Record last verified: 2022-06

Data Sharing

• IPD Sharing: Will not share

Locations

DK (2)