Neuroprotective Goal Directed Hemodynamic Optimization in Post-cardiac Arrest Patients (NEUROPROTECT)

Neuroprotective Goal Directed Hemodynamic Optimization in Post-cardiac Arrest Patients: a Randomized Controlled Trial (the NEUROPROTECT Post-CA Trial)

The primary objective of the Neuroprotect trial is to assess whether or not a new goal directed hemodynamic optimization strategy can reduce cerebral ischemia in post-cardiac arrest (CA) patients.

Study Overview

• Status: Completed
• Conditions: Cardiac Arrest; Cerebral Ischemia
• Intervention / Treatment: Other: Neuroprotective goal directed hemodynamic optimization; Other: MAP > 65mmHg

Detailed Description

Unconscious patients admitted to the intensive care unit after being successfully resuscitated from cardiac arrest (CA) are at high risk for death, and neurological deficits are common among survivors. Nevertheless, the optimal hemodynamic strategy to ensure optimal cerebral perfusion and maximal outcome has not been studied by a randomized controlled trial. In the absence of good evidence, current post-CA guidelines are adapted from sepsis guidelines and recommend targeting a mean arterial pressure (MAP) above 65 mmHg (Peberdy ea, Circulation 2010). Importantly, post-CA patients have a large cerebral penumbra at risk for infarction when resuscitated to suboptimal MAP's. In a large subset of post-CA patients the lower threshold of cerebral autoregulation is shifted rightward and these patients might benefit from resuscitation to higher MAP's (Sundgreen ea, Stroke 2001) in order to ensure adequate cerebral oxygenation. Our research group previously showed that a MAP of 85-100mmHg results in optimal cerebral perfusion in post-CA patients (Ameloot ea, resuscitation 2015). Two retrospective and 2 prospective observational studies suggested an association between higher MAP's and better outcome in post-CA patients (Ameloot ea, resuscitation 2015). However, the value of these trials is limited by their observational design. The question remains as to whether patients with higher MAP's do have a better outcome due to more optimal cerebral perfusion and less cerebral damage or whether a higher MAP is merely a non-causal marker of more limited disease severity in these patients. In other words, the primary research question is whether we can reduce cerebral ischemia and improve prognosis of post-cardiac arrest survivors by targeting higher mean systemic blood pressures thereby optimizing cerebral perfusion during their stay in the intensive care unit. To answer this, we propose a multicenter interventional open label investigator driven randomized controlled trial to compare a goal-directed potentially neuro-protective hemodynamic optimization strategy with the current standard of care. Primary efficacy endpoints of the study will include extent of cerebral damage as assessed with diffusion weighted magnetic resonance imaging (DW-MRI), functional and neurocognitive testing, biomarkers of brain injury and survival rates. The final utilization goal of the Neuroprotect post-CA trial is to show that our adapted hemodynamic protocol reduces cerebral ischemia, and improves survival and functional outcome of post-cardiac arrest patients.

• Study Type: Interventional
• Enrollment (Actual): 112
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Belgium
  • Genk, Belgium, 3600
    • Ziekenhuis Oost Limburg
  • Leuven, Belgium, 3000
    • UZ Leuven

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Out-of-hospital CA of presumed cardiac cause irrespective of the presenting rhythm
2. Unconsciousness (Glasgow coma scale < 8) at hospital admission
3. Age ≥ 18 years
4. Sustained return of spontaneous circulation (ROSC) (=when chest compressions have not been required for 20 consecutive minutes)

Exclusion Criteria:

1. Suspected or confirmed intracranial bleeding or stroke
2. Known limitations in therapy or Do Not Resuscitate-order
3. Known disease compromising 180 day survival
4. Known pre-CA cerebral performance category 3-4
5. Previous stroke (TIA can be included)
6. MRI incompatible cardiac or neurosurgical device
7. Systolic blood pressure < 90 mmHg on norepinephrine > 1 mcg/kg/min).
8. Open chest
9. ECMO (extracorporeal membrane oxygenation)
10. Pregnancy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Neuroprotect; MAP between 85-100mmHg SVO2 between 65-75%	Other: Neuroprotective goal directed hemodynamic optimization
Active Comparator: Control; MAP>65mmHg	Other: MAP > 65mmHg; MAP > 65mmHg

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
% of Ischaemic Voxels With an ADC<0.65 mm2/s on Day 4-5 (Diffusion Weighted MRI)	cerebral ischemia in post-cardiac arrest (CA) patients as quantified by the apparent diffusion coefficient (ADC) on diffusion weighted MRI (DW-MRI) to be performed at day 4- 5 post-CA using ADC scores in 11 pre-specified brain regions (frontal cortex, parietal cortex, temporal cortex, occipital cortex, precentral cortex, postcentral cortex, caudate nucleus, putamen, thalamus, cerebellum, pons).	day 4-5

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
diffusion weighted MRI	o Percentage of voxels under a suggested ADC threshold of 0.650x10-3 mm2/s	day 4-5
Diffusion weighted MRI	o Whole brain median ADC score [mm2/s]	day 4-5
CPC	o Cerebral performance category 3-5 at 180 days post-CA	180 days after admission
The Short Form (36) Health Survey	o SF36 questionnaire at 180 days post-CA	180 days after admission
Neurocognitive testing	Neurocognitive testing at discharge from the hospital by the adult verbal learning test	discharge from the hospital (expected time frame 2-4 weeks after admission)
Neurocognitive testing	Neurocognitive testing at discharge from the hospital by the digit span backwards test	discharge from the hospital (expected time frame 2-4 weeks after admission)
Neurocognitive testing	Neurocognitive testing at discharge from the hospital by the red pencil test	discharge from the hospital (expected time frame 2-4 weeks after admission)
Neurocognitive testing	Neurocognitive testing at discharge from the hospital by the Wechsler Memory Scale Revised test	discharge from the hospital (expected time frame 2-4 weeks after admission)
Biomarkers	Neuron specific enolase (day 1-2-3-4-5)	day 1-2-3-4-5
Functional testing	Activities Daily Life (ADL)	Discharge from the hospital (expected time frame 2-4 weeks after admission)
Functional testing	6 minute walking distance (6MWD) at discharge from the hospital	Discharge from the hospital (expected time frame 2-4 weeks after admission)
ICU parameters	lenght of stay in ICU [number of days]	At ICU discharge (expected time frame 1-2 weeks after admission)
ICU parameters	Ventilator days [number of days]	At ICU discharge (expected time frame 1-2 weeks after admission)
ICU parameters	tracheostomy performed (yes/no)	At ICU discharge (expected time frame 1-2 weeks after admission)
Renal function	creatinine [mg/dl]	day 1-2-3-4-5

Collaborators and Investigators

• Sponsor: Universitaire Ziekenhuizen KU Leuven
• Collaborators: Ziekenhuis Oost-Limburg
• Investigators: Principal Investigator: Koen Ameloot, MD, UZ Leuven; Principal Investigator: Stefan Janssens, MD, UZ Leuven; Principal Investigator: Joseph Dens, MD, Ziekenhuis Oost-Limburg; Principal Investigator: Cathy De Deyne, MD, Ziekenhuis Oost-Limburg

Publications and helpful links

General Publications

• Wouters A, Scheldeman L, Plessers S, Peeters R, Cappelle S, Demaerel P, Van Paesschen W, Ferdinande B, Dupont M, Dens J, Janssens S, Ameloot K, Lemmens R. Added Value of Quantitative Apparent Diffusion Coefficient Values for Neuroprognostication After Cardiac Arrest. Neurology. 2021 May 25;96(21):e2611-e2618. doi: 10.1212/WNL.0000000000011991. Epub 2021 Apr 9.
• 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.

Study record dates

Study Major Dates

• Study Start: August 1, 2015
• Primary Completion (Actual): June 1, 2018
• Study Completion (Actual): June 1, 2018

Study Registration Dates

• First Submitted: August 27, 2015
• First Submitted That Met QC Criteria: September 1, 2015
• First Posted (Estimated): September 4, 2015

Study Record Updates

• Last Update Posted (Actual): April 12, 2024
• Last Update Submitted That Met QC Criteria: October 20, 2023
• Last Verified: June 1, 2018

More Information

Terms related to this study

• Keywords: hemodynamics; post cardiac arrest
• Additional Relevant MeSH Terms: Pathologic Processes; Necrosis; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Infarction; Stroke; Brain Infarction; Brain Ischemia; Ischemia; Heart Arrest; Cerebral Infarction
• Other Study ID Numbers: s58017

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No