Carbon Dioxide, Oxygen and Mean Arterial Pressure After Cardiac Arrest and Resuscitation

NCT02698917 | Completed

• 1 other identifier: 15/2015
• Study Type: interventional
• Target: 123
• Locations: 2 countries
• Sites: 7

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.

Conditions

Out-of-Hospital Cardiac Arrest

Keywords

Out-of-Hospital Cardiac Arrest; Resuscitation; Hypoxia-Ischemia, Brain

Outcome Measures

Primary Outcomes (1)

• Neuron-specific enolase (NSE) serum concentration

  48 hour after cardiac arrest

Secondary Outcomes (6)

• Neuron-specific enolase (NSE) serum concentration

  At randomization and 24 and 72 hour after cardiac arrest

• S100B protein serum concentration

  At randomization and 24, 48 and 72 hour after cardiac arrest

• Cardiac troponin (TnT) serum concentration

  At randomization and 24, 48 and 72 hour after cardiac arrest

• Cerebral oxygenation monitoring using near infrared spectroscopy (NIRS) monitoring

  For 48 hour after admission to ICU

• Continuous electroencephalography (EEG) monitoring

  For 48 hour after admission to ICU

Other Outcomes (3)

• Between-group separation in PaCO2

  Every 3 hour for 36 hour after admission to ICU

• Between-group separation in PaO2

  Every 3 hour for 36 hour after admission to ICU

• Between-group separation in MAP

  Every 1 hour for 36 hour after admission to ICU

Study Arms (8)

Group 1

ACTIVE COMPARATOR

Low normal PaCO2, low normal PaO2, low normal MAP

Other: Low normal PaCO2; Other: Low normal PaO2; Other: Low normal MAP

Group 2

ACTIVE COMPARATOR

High normal PaCO2, low normal PaO2, low normal MAP

Other: High normal PaCO2; Other: Low normal PaO2; Other: Low normal MAP

Group 3

ACTIVE COMPARATOR

Low normal PaCO2, high normal PaO2, low normal MAP

Other: Low normal PaCO2; Other: High normal PaO2; Other: Low normal MAP

Group 4

ACTIVE COMPARATOR

High normal PaCO2, high normal PaO2, low normal MAP

Other: High normal PaCO2; Other: High normal PaO2; Other: Low normal MAP

Group 5

ACTIVE COMPARATOR

Low normal PaCO2, low normal PaO2, high normal MAP

Other: Low normal PaCO2; Other: Low normal PaO2; Other: High normal MAP

Group 6

ACTIVE COMPARATOR

High normal PaCO2, low normal PaO2, high normal MAP

Other: High normal PaCO2; Other: Low normal PaO2; Other: High normal MAP

Group 7

ACTIVE COMPARATOR

Low normal PaCO2, high normal PaO2, high normal MAP

Other: Low normal PaCO2; Other: High normal PaO2; Other: High normal MAP

Group 8

ACTIVE COMPARATOR

High normal PaCO2, high normal PaO2, high normal MAP

Other: High normal PaCO2; Other: High normal PaO2; Other: High normal MAP

Interventions

Low normal PaCO2 OTHER

4.5-4.7 kPa

Group 1; Group 3; Group 5; Group 7

High normal PaCO2 OTHER

5.8-6.0 kPa

Group 2; Group 4; Group 6; Group 8

Low normal PaO2 OTHER

10-15 kPa

Group 1; Group 2; Group 5; Group 6

High normal PaO2 OTHER

20-25 kPa

Group 3; Group 4; Group 7; Group 8

Low normal MAP OTHER

65-75 mmHg

Group 1; Group 2; Group 3; Group 4

High normal MAP OTHER

80-100 mmHg

Group 5; Group 6; Group 7; Group 8

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Helsinki University Central Hospital: lead
• Laerdal Foundation: collaborator
• The Finnish Medical Association: collaborator
• Orion Research Foundation: collaborator
• Finnish Society of Anaesthesiologists: collaborator

Study Sites (7)

Aarhus University Hospital

Aarhus, Denmark

Location

Helsinki University Hospital

Helsinki, Finland

Location

North Karelia Central Hospital

Joensuu, Finland

Location

Central Finland Central Hospital

Jyväskylä, Finland

Location

Kuopio University Hospital

Kuopio, Finland

Location

Päijät-Häme Central Hospital

Lahti, Finland

Location

Tampere University Hospital

Tampere, Finland

Location

Related Publications (7)

• Laurikkala J, Ameloot K, Reinikainen M, Palmers PJ, De Deyne C, Bert F, Dupont M, Janssens S, Dens J, Hastbacka J, Jakkula P, Loisa P, Birkelund T, Wilkman E, Vaara ST, Skrifvars MB. The effect of higher or lower mean arterial pressure on kidney function after cardiac arrest: a post hoc analysis of the COMACARE and NEUROPROTECT trials. Ann Intensive Care. 2023 Nov 21;13(1):113. doi: 10.1186/s13613-023-01210-0.

  PMID: 37987871 DERIVED

• 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.

  PMID: 34863908 DERIVED

• 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.

  PMID: 34583763 DERIVED

• 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.

  PMID: 32792079 DERIVED

• 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.

  PMID: 31088512 DERIVED

• 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.

  PMID: 30430209 DERIVED

• 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.

  PMID: 29084585 DERIVED

MeSH Terms

Conditions

Out-of-Hospital Cardiac Arrest; Hypoxia-Ischemia, Brain

Condition Hierarchy (Ancestors)

Heart Arrest; Heart Diseases; Cardiovascular Diseases; Brain Ischemia; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Hypoxia, Brain; Vascular Diseases; Hypoxia; Signs and Symptoms, Respiratory; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• Matti Reinikainen, Associate Professor

  Kuopio University Hospital

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: The physician determining neurological outcome at six months after cardiac arrest is blinded to the study group allocations
• Purpose: TREATMENT
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD

Study Record Dates

• First Submitted: January 26, 2016
• First Posted: March 4, 2016
• Study Start: March 22, 2016
• Primary Completion: November 3, 2017
• Study Completion: May 3, 2018
• Last Updated: August 3, 2018

Record last verified: 2018-08

Locations

DK (1); FI (6)