Cardiac Arrest, Ischemia Reperfusion Injury, Anoxic Brain Injury
Conditions
Keywords
sodium lactate, cerebral metabolism
Brief summary
The study is intended to test the hypothesis that sodium lactate infusion after resuscitation from a cardiac arrest will decrease the magnitude of brain damage, as measured by the serum biomarker concentration of NSE.
Detailed description
Background: In resuscitated patients after cardiac arrest, ischemic brain injury and cardiac depression due to the reperfusion injury are accountable for high mortality rate and poor outcome. Hypertonic sodium lactate (HSL) solutions have been proven to be safe in healthy volunteers and they have shown some benefits in patients with traumatic brain injury and those with myocardial ischemia and could decrease the burden of hypoxic lesions in these organs. The aim of this phase II study is to investigate whether HSL administration could reduce organ damage related biomarkers in serum and if the administrations of these solutions is safe and feasible in resuscitated patients after cardiac arrest. Design: an investigator initiated, randomized, controlled, open label phase II clinical trial to test the safety and efficacy of the infusion of HSL in resuscitated patients after cardiac arrest admitted to the hospital. After resuscitation from CA, comatose patients will be screened for eligibility and randomized to receive either study treatment as HSL 1M infusion for 24h or standard of care. Expected outcomes: This controlled trial will assess the safety and efficacy of the 1M HSL infusion in a cohort of comatose resuscitated patients after cardiac arrest. The results of this trial may provide useful information for a larger phase III clinical trial.
Interventions
continuous intravenous infusion of molar sodium lactate
Sponsors
Erasme University Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age \> 18 years old * Sustained (\> 20 minutes) return of spontaneous circulation (ROSC) * Comatose (GCS \< 9) * Time to ROSC \> 15'
Exclusion criteria
* Protected categories (Pregnant women) * Anticipated withdrawal of support within 24 hours * Traumatic cause of cardiac arrest * Body weight at admission \> 120Kg
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| serum NSE | 48 hours after randomization | NSE serum levels |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mortality | trough study completion before hospital discharge, on average 90 days | mortality |
| Neurological outcome | trough study completion, 90 days after randomization | Neurological outcome measured by Cerebral Performance Category score at 90 days (1-5, 1 meaning better Neurological outcome) |
| Hospital length of stay | trough study completion, on average 60 days | Hospital length of stay |
| Vasopressors equivalent dose | through study completion, during the first 48 hours after resuscitation | Vasopressors equivalent dose during the first 48 hours after resuscitation |
| Seizure rate | through study completion before ICU discharge, on average 14 days | Seizure rate |
| Changes in cardiac biomarkers | at randomization, 24 hours, 48 hours and 72 hours after randomization | Troponin I serum levels |
| Changes in brain biomarkers | at randomization, after 24 hours, 48 hours and 72 hours | brain biomarkers including nfL and GFAP |
| ICU length of stay | trough study completion, on average 30 days | number of days in the intensive care unit |
| Changes in brain metabolism | within 24h after randomization | Brain metabolism measured by PET-IRM |
| Changes in brain perfusion | within 24h after randomization | brain perfusion measured with early perfusion CT scan |
| Changes in echocardiographic parameters (systolic) | at randomization, at 24 hours and 48 hours after randomization | Changes systolic cardiac function assessed by echocardiography |
| Changes in echocardiographic parameters (diastolic) | at randomization, at 24 hours and 48 hours after randomization | Changes diastolic cardiac function assessed by echocardiography |
| identification of optimal perfusion pressure | through study completion, on average 30 days | identification of optimal perfusion pressure with invasive neuromonitoring |
| identification of optimal cerebral oxygen tension | through study completion, on average 30 days | identification of optimal cerebral oxygen tension with invasive neuromonitoring |
| Severe adverse events rate | during study drug administration/day 28 or ICU discharge or death | Serious adverse events rate |
Countries
Belgium
Contacts
Primary ContactFilippo Annoni, MD
Backup ContactFabio S Taccone, MD,PhD
Outcome results
None listed