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Neuroprotective Goal Directed Hemodynamic Optimization in Post-cardiac Arrest Patients

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

Status
Completed
Phases
NA
Study type
Interventional
Source
ClinicalTrials.gov
Registry ID
NCT02541591
Acronym
NEUROPROTECT
Enrollment
112
Registered
2015-09-04
Start date
2015-08-31
Completion date
2018-06-30
Last updated
2024-04-12

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Cardiac Arrest, Cerebral Ischemia

Keywords

post cardiac arrest, hemodynamics

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.

Interventions

OTHERNeuroprotective goal directed hemodynamic optimization
OTHERMAP > 65mmHg

MAP \> 65mmHg

Sponsors

Ziekenhuis Oost-Limburg
CollaboratorOTHER
Universitaire Ziekenhuizen KU Leuven
Lead SponsorOTHER

Study design

Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE

Eligibility

Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No

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

Design outcomes

Primary

MeasureTime frameDescription
% of Ischaemic Voxels With an ADC<0.65 mm2/s on Day 4-5 (Diffusion Weighted MRI)day 4-5cerebral 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).

Countries

Belgium

Participant flow

Recruitment details

Emergency care

Participants by arm

ArmCount
Neuroprotect
MAP between 85-100mmHg SVO2 between 65-75% Neuroprotective goal directed hemodynamic optimization
52
Control
MAP\>65mmHg MAP \> 65mmHg: MAP \> 65mmHg
55
Total107

Baseline characteristics

CharacteristicControlTotalNeuroprotect
Age, Categorical
<=18 years
0 Participants0 Participants0 Participants
Age, Categorical
>=65 years
28 Participants54 Participants26 Participants
Age, Categorical
Between 18 and 65 years
27 Participants53 Participants26 Participants
Age, Continuous65 years
STANDARD_DEVIATION 13
65 years
STANDARD_DEVIATION 12
64 years
STANDARD_DEVIATION 12
Race and Ethnicity Not Collected0 Participants
Region of Enrollment
Belgium
55 participants107 participants52 participants
Sex: Female, Male
Female
13 Participants26 Participants13 Participants
Sex: Female, Male
Male
42 Participants81 Participants39 Participants

Adverse events

Event typeEG000
affected / at risk
EG001
affected / at risk
deaths
Total, all-cause mortality
31 / 5229 / 55
other
Total, other adverse events
0 / 520 / 55
serious
Total, serious adverse events
7 / 5221 / 55

Outcome results

Primary

% 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).

Time frame: day 4-5

Population: Full Analysis Set

ArmMeasureValue (MEDIAN)
Neuroprotect% of Ischaemic Voxels With an ADC<0.65 mm2/s on Day 4-5 (Diffusion Weighted MRI)10.6 percentage of ischaemic voxels
Control% of Ischaemic Voxels With an ADC<0.65 mm2/s on Day 4-5 (Diffusion Weighted MRI)11.0 percentage of ischaemic voxels
Comparison: missing data were accounted for by multiple imputationp-value: 0.088195% CI: [0.95, 1.98]ANOVA

Source: ClinicalTrials.gov · Data processed: Mar 9, 2026