Hypertonic Lactate After Cardiac Arrest

Study Overview
=================
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 0.5M infusion for 24h or standard of care. Expected outcomes: This controlled trial will assess the safety and efficacy of the 0.5 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.

Official Title
-----------------
Hypertonic Lactate After Cardiac Arrest

Conditions
-----------------
Cardiac Arrest, Ischemia Reperfusion Injury, Anoxic Brain Injury

Intervention / Treatment
-----------------
* Drug: Sodium Lactate Solution


Participation Criteria
=================
Eligibility Criteria
-----------------
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, Prisoners) Anticipated withdrawal of support within 24 hours Traumatic cause of cardiac arrest time from ROSC to inclusion > 1hour Inclusion in any other interventional trial

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: standard of care<br>Patients will receive the standard of care infusion (balanced crystalloids) | |
| Experimental: treatement group<br>half molar sodium lactate infusion 15 µmol/Kg/min | Drug: Sodium Lactate Solution<br>* continuous intravenous infusion of half-molar sodium lactate<br>* Other names: Hyperonic sodium lactate;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| serum NSE | NSE serum levels | 48 hours after randomization | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ICU free days | number of days free from intensive care unit | trough study completion, on average 30 days | 
| Mortality | mortality | trough study completion before hospital discharge, on average 60 days | 
| Neurological outcome | Neurological outcome measured by Glasgow Outcome Scale at 90 days | trough study completion, 90 days after randomization | 
| Hospital length of stay | Hospital length of stay | trough study completion, on average 60 days | 
| Severe adverse events rate | Serious adverse events rate | during study drug administration/day 28 or ICU discharge or death | 
| Need for Vasopressors | Need for vasopressors during hospitalization | through study completion, on average 14 days | 
| Seizure rate | Seizure rate | through study completion before ICU discharge, on average 14 days | 
| Changes in cardiac biomarkers | Troponin I serum levels | at randomization, 24 hours, 48 hours and 72 hours after randomization | 
| Changes in brain biomarkers | brain biomarkers including nfL and GFAP | at randomization, after 24 hours, 48 hours and 72 hours | 
| Changes in brain metabolism | Brain metabolism measured by PET-IRM | within 24h after randomization | 
| Changes in brain perfusion | brain perfusion measured with early perfusion CT scan | within 24h after randomization | 
| Changes in echocardiographic parameters (systolic) | Changes systolic cardiac function assessed by echocardiography | at randomization, at 24 hours and 48 hours after randomization | 
| Changes in echocardiographic parameters (diastolic) | Changes diastolic cardiac function assessed by echocardiography | at randomization, at 24 hours and 48 hours after randomization | 
| identification of optimal perfusion pressure | identification of optimal perfusion pressure with invasive neuromonitoring | through study completion, on average 30 days | 
| identification of optimal cerebral oxygen tension | identification of optimal cerebral oxygen tension with invasive neuromonitoring | through study completion, on average 30 days | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
sodium lactate, cerebral metabolism