Clinical trial NCT02541591: Neuroprotective Goal Directed Hemodynamic Optimization in Post-cardiac Arrest Patients
Official title: Neuroprotective Goal Directed Hemodynamic Optimization in Post-cardiac Arrest Patients: a Randomized Controlled Trial (the NEUROPROTECT Post-CA Trial)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Cerebral Ischemia
Cardiac Arrest
Keywords: post cardiac arrest
hemodynamics
Lead sponsor: Universitaire Ziekenhuizen KU Leuven
Sponsor class: OTHER
Collaborators: name: Ziekenhuis Oost-Limburg
First posted: 2015-09-04
Enrollment: 112
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Eligibility 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

Primary outcomes:
measure: % of Ischaemic Voxels With an ADC<0.65 mm2/s on Day 4-5 (Diffusion Weighted MRI)
timeFrame: day 4-5
Secondary outcomes:
Other outcomes:
Locations:
city: Genk
country: Belgium
facility: Ziekenhuis Oost Limburg
city: Leuven
country: Belgium
facility: UZ Leuven
Study officials:
affiliation: UZ Leuven
name: Koen Ameloot, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: UZ Leuven
name: Stefan Janssens, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Ziekenhuis Oost-Limburg
name: Joseph Dens, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Ziekenhuis Oost-Limburg
name: Cathy De Deyne, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
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.