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

• ClinicalTrials.gov Identifier: NCT02541591
• Recruitment Status: Completed
• First Posted: September 4, 2015
• Last Update Posted: June 26, 2018
• Sponsor: Universitaire Ziekenhuizen Leuven
• Collaborator: Ziekenhuis Oost-Limburg
• Information provided by (Responsible Party): Universitaire Ziekenhuizen Leuven

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Cerebral Ischemia; Cardiac Arrest	Other: Neuroprotective goal directed hemodynamic optimization; Other: MAP > 65mmHg	Not Applicable

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 112 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Neuroprotective Goal Directed Hemodynamic Optimization in Post-cardiac Arrest Patients: a Randomized Controlled Trial (the NEUROPROTECT Post-CA Trial)
• Study Start Date: August 2015
• Actual Primary Completion Date: June 2018
• Actual Study Completion Date: June 2018

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. Diffusion weighted MRI [ Time Frame: day 4-5 ]
   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).

Secondary Outcome Measures :

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

Eligibility Criteria

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

Criteria

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

Contacts and Locations

Locations

Belgium

Ziekenhuis Oost Limburg

Genk, Belgium, 3600

UZ Leuven

Leuven, Belgium, 3000

Sponsors and Collaborators

Universitaire Ziekenhuizen Leuven

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

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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, Hästbacka J, Reinikainen M, Pettilä 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.

• Responsible Party: Universitaire Ziekenhuizen Leuven
• ClinicalTrials.gov Identifier: NCT02541591
• Other Study ID Numbers: s58017
• First Posted: September 4, 2015
• Last Update Posted: June 26, 2018
• Last Verified: June 2018

Keywords provided by Universitaire Ziekenhuizen Leuven:

post cardiac arrest; hemodynamics

Additional relevant MeSH terms:

Brain Ischemia; Cerebral Infarction; Heart Arrest; Ischemia; Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Brain Infarction; Stroke; Infarction; Necrosis