Clinical trial NCT02698917: Carbon Dioxide, Oxygen and Mean Arterial Pressure After Cardiac Arrest and Resuscitation
Official title: Carbon Dioxide, Oxygen and Mean Arterial Pressure After Cardiac Arrest and Resuscitation - Targeting High vs. Low Normal Values
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Out-of-Hospital Cardiac Arrest
Keywords: Out-of-Hospital Cardiac Arrest
Resuscitation
Hypoxia-Ischemia, Brain
Lead sponsor: Helsinki University Central Hospital
Sponsor class: OTHER
Collaborators: name: Laerdal Foundation
name: The Finnish Medical Association
name: Orion Research Foundation
name: Finnish Society of Anaesthesiologists
First posted: 2016-03-04
Enrollment: 123
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: FACTORIAL
Primary purpose: TREATMENT

Brief summary: The COMACARE trial is a pilot multicenter randomized trial to assess the feasibility and effect on brain injury markers of targeting low or high normal arterial oxygen tension (PaO2), arterial carbon dioxide tension (PaCO2) and mean arterial pressure (MAP) in comatose, mechanically ventilated patients after out-of-hospital cardiac arrest. Using factorial design, participants are randomized at admission to intensive care unit to one of eight groups targeting either low or high normal values of PaO2, PaCO2 and MAP for 36 h. In this way, investigators will be assessing the feasibility and effect of all three variables at the same time.

The primary outcome is serum concentration of neuron-specific enolase (NSE) at 48 h after cardiac arrest. Feasibility outcome is between-group separation in PaO2, PaCO2 and MAP levels. Secondary outcomes include continuous monitoring of cerebral oxygenation, EEG and ECG for 48 h, the levels of NSE, S100B and cardiac troponin at randomization and 24, 48 and 72 h after cardiac arrest and neurological assessment at 6 months after cardiac arrest.


Eligibility criteria: Inclusion Criteria:

* Witnessed out-of-hospital cardiac arrest with ventricular fibrillation (VF) or ventricular tachycardia (VT) as the initial rhythm
* Delay of return of spontaneous circulation (ROSC) 10-45 min from the start of the arrest
* Confirmed or suspected cardiac origin
* Mechanical ventilation
* Markedly impaired level of consciousness (no response to verbal commands and Glasgow coma scale \[GCS\] motor score \< 5)
* Deferred consent possible or likely
* Active intensive care initiated, including targeted temperature management (33-36 C)

Exclusion Criteria:

* Probable withdrawal of active ICU care due to terminal illness or poor prognosis because of severely reduced functional status before cardiac arrest
* Confirmed or suspected intracranial pathology and/or suspicion of raised intracranial pressure
* Pregnancy
* Severe oxygenation problem (PaO2 / FiO2 \< 100 mmHg)
* Severe COPD

Primary outcomes:
measure: Neuron-specific enolase (NSE) serum concentration
timeFrame: 48 hour after cardiac arrest
Secondary outcomes:
measure: Neuron-specific enolase (NSE) serum concentration
timeFrame: At randomization and 24 and 72 hour after cardiac arrest
measure: S100B protein serum concentration
timeFrame: At randomization and 24, 48 and 72 hour after cardiac arrest
measure: Cardiac troponin (TnT) serum concentration
timeFrame: At randomization and 24, 48 and 72 hour after cardiac arrest
measure: Cerebral oxygenation monitoring using near infrared spectroscopy (NIRS) monitoring
timeFrame: For 48 hour after admission to ICU
measure: Continuous electroencephalography (EEG) monitoring
timeFrame: For 48 hour after admission to ICU
measure: Functional status using cerebral performance category (CPC) classification
timeFrame: At 30 days and 6 months after cardiac arrest
Other outcomes:
measure: Between-group separation in PaCO2
timeFrame: Every 3 hour for 36 hour after admission to ICU
measure: Between-group separation in PaO2
timeFrame: Every 3 hour for 36 hour after admission to ICU
measure: Between-group separation in MAP
timeFrame: Every 1 hour for 36 hour after admission to ICU
Locations:
city: Aarhus
country: Denmark
facility: Aarhus University Hospital
city: Helsinki
country: Finland
facility: Helsinki University Hospital
city: Joensuu
country: Finland
facility: North Karelia Central Hospital
city: Jyväskylä
country: Finland
facility: Central Finland Central Hospital
city: Kuopio
country: Finland
facility: Kuopio University Hospital
city: Lahti
country: Finland
facility: Päijät-Häme Central Hospital
city: Tampere
country: Finland
facility: Tampere University Hospital
Study officials:
affiliation: Kuopio University Hospital
name: Matti Reinikainen, Associate Professor
role: STUDY_DIRECTOR
References:
citation: Humaloja J, Lahde M, Ashton NJ, Reinikainen M, Hastbacka J, Jakkula P, Friberg H, Cronberg T, Pettila V, Blennow K, Zetterberg H, Skrifvars MB; COMACARE Study Groups. GFAp and tau protein as predictors of neurological outcome after out-of-hospital cardiac arrest: A post hoc analysis of the COMACARE trial. Resuscitation. 2022 Jan;170:141-149. doi: 10.1016/j.resuscitation.2021.11.033. Epub 2021 Dec 1.
citation: Laurikkala J, Aneman A, Peng A, Reinikainen M, Pham P, Jakkula P, Hastbacka J, Wilkman E, Loisa P, Toppila J, Birkelund T, Blennow K, Zetterberg H, Skrifvars MB. Association of deranged cerebrovascular reactivity with brain injury following cardiac arrest: a post-hoc analysis of the COMACARE trial. Crit Care. 2021 Sep 28;25(1):350. doi: 10.1186/s13054-021-03764-6.
citation: Ameloot K, Jakkula P, Hastbacka J, Reinikainen M, Pettila V, Loisa P, Tiainen M, Bendel S, Birkelund T, Belmans A, Palmers PJ, Bogaerts E, Lemmens R, De Deyne C, Ferdinande B, Dupont M, Janssens S, Dens J, Skrifvars MB. Optimum Blood Pressure in Patients With Shock After Acute Myocardial Infarction and Cardiac Arrest. J Am Coll Cardiol. 2020 Aug 18;76(7):812-824. doi: 10.1016/j.jacc.2020.06.043.
citation: Jakkula P, Hastbacka J, Reinikainen M, Pettila V, Loisa P, Tiainen M, Wilkman E, Bendel S, Birkelund T, Pulkkinen A, Backlund M, Heino S, Karlsson S, Kopponen H, Skrifvars MB. Near-infrared spectroscopy after out-of-hospital cardiac arrest. Crit Care. 2019 May 14;23(1):171. doi: 10.1186/s13054-019-2428-3.
citation: Jakkula P, Reinikainen M, Hastbacka J, Loisa P, Tiainen M, Pettila V, Toppila J, Lahde M, Backlund M, Okkonen M, Bendel S, Birkelund T, Pulkkinen A, Heinonen J, Tikka T, Skrifvars MB; COMACARE study group. Targeting two different levels of both arterial carbon dioxide and arterial oxygen after cardiac arrest and resuscitation: a randomised pilot trial. Intensive Care Med. 2018 Dec;44(12):2112-2121. doi: 10.1007/s00134-018-5453-9. Epub 2018 Nov 14.
citation: Jakkula P, Reinikainen M, Hastbacka J, Pettila V, Loisa P, Karlsson S, Laru-Sompa R, Bendel S, Oksanen T, Birkelund T, Tiainen M, Toppila J, Hakkarainen A, Skrifvars MB; COMACARE study group. Targeting low- or high-normal Carbon dioxide, Oxygen, and Mean arterial pressure After Cardiac Arrest and REsuscitation: study protocol for a randomized pilot trial. Trials. 2017 Oct 30;18(1):507. doi: 10.1186/s13063-017-2257-0.