Caffeinol Hypothermia Protocol

Study Overview
=================
Brief Summary
-----------------
Caffeinol is a combination of caffeine and alcohol. The amount given is about the same as 1-2 glasses of wine and 3-4 cups of coffee. The patient receives a one time dose given over two hour while being cooled to 34.5 C.

Official Title
-----------------
Combined Neuroprotective Modalities Coupled With Thrombolysis in Acute Ischemic Stroke: A Pilot Study of Caffeinol and Mild Hypothermia

Conditions
-----------------
Acute Ischemic Stroke

Intervention / Treatment
-----------------
* Drug: Caffeinol
* Procedure: hypothermia


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Age 18-80 years Clinical presentation of acute ischemic stroke Computed tomography (CT) scan compatible with acute ischemic stroke. Time to caffeinol treatment < 240 minutes from stroke onset. Time to hypothermia initiation < 300 minutes from stroke onset. Presumed cortical location of stroke (must have at least on sign such as aphasia, neglect, visual field cut) National Institutes of Health Stroke Scale (NIHSS) > 8 at time of each treatment. Tissue plasminogen activator (TPA) treated patients must meet all established criteria for TPA. Exclusion Criteria: Etiology other than ischemic stroke. Item 1a on NIHSS > 1 Signs/symptoms of subcortical, brainstem or cerebellar stroke. Symptoms resolving or NIHSS < 8 at time of each treatment. NIHSS > 20 if right hemisphere or >25 if left hemisphere Known alcoholic Clinical or laboratory evidence of alcohol intoxication. Historical evidence of exogenous caffeine exposure beyond daily consumption of coffee or soft drinks. Known hematologic dyscrasias that affect thrombosis. Comorbid conditions likely to complicate therapy: End-stage cardiomyopathy Uncompensated or clinically significant arrhythmia Myopathy Liver disease History of pelvic or abdominal mass likely to compress inferior vena cava. End-stage AIDS History of clinically significant gastrointestinal (GI) bleeding Impaired renal function with creatinine clearance, 50 ml/min Intracerebral / intraventricular hemorrhage Systolic blood pressure (SBP) > 210 or < 100; diastolic blood pressure (DBP) > 100 or < 50 mmHg Severe coagulopathy Pregnancy Use of monoamine oxidase inhibitor (MAOI),serotonin-specific reuptake inhibitor (SSRI) or Tricyclic Antidepressants (TCA) within the preceding 2 weeks Known history of epilepsy.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 80 Years

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

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

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

Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: Caffeinol|Infusion of caffeinol (9mg/kg caffeine + 0.4g/kg ethanol) over 2 hours.|
|Procedure: hypothermia|External or internal cooling for 24 hours and rewarming over 12 hours.|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Symptomatic Intracerebral Hemorrhage | Symptomatic intracerebral hemorrhages were measured by a full NIHSS(National Institute of Health Stroke Scale) prior to caffeinol & hypothermia,at the end of hypothermia & rewarming, 24 hrs after stroke onset, daily during hospitalization,& at the 90 day follow-up visit. In addition, modified NIHSS were done hourly during the 24 hr hypothermia period & 12 hr rewarming period. At the end of rewarming an MRI was obtained to verify if hemorrhages or neurologic deteriorations were present.NIHSS scores severity of stroke on 11 items;more points given for greater deficiencies(range 0-42,0=normal) | from pre-dosage to 90 day followup | 
| Number of Participants With Catheter Related Complications During Hypothermia & Rewarming | Catheter-related complications assessed whether participants had bleeding (major hemorrhaging) that required a blood transfusion, this was determined by labs. Participants were monitored for infections every hour during vital signs in the 24 hour hypothermia phase and 12 hour rewarming phase. | over 36 hour period | 
| Number of Participants With Cardiorespiratory Failure | The possibility of cardiorespiratory failure was monitored every 30 minutes during the 24 hour hypothermia period based on vitals signs and oxygen saturation. | every 30 minutes during hypothermia induction | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Feasibility: Time Required to Reach the Target Core Temperature or Lowest Tolerated Temperature, Stability of Patient Temperature, Control of Rewarming, | Hypothermia will be maintained for 24 hours, afterward, the patient will be rewarmed, gradually, over 12 hours to 36.5C. | rewarming over 12 hours until 36.5C has been achieved | 
| Achievement of Therapeutic Serum Ethanol and Caffeine Levels, and Amount of Sedation Needed to Suppress Shivering. |  | rewarming over 12 hours until 36.5C has been achieved | 
| Efficacy: NIHSS < 2 at 24 Hours, Modified Rankin Scale (mRS) < 2 at 3 Months, NIHSS < 2 at 3 Months, and Length of Hospital and ICU Stay. | NIHSS score of ≤ 2 24 hours after stroke onset modified Rankin Scale (mRS) < 2 at 90 day followup NIHSS score of ≤ 2 at daily duration of hospitalization and ICU stay and 90 day follow up. | 90 days | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Stroke, Nonhemorrhagic, hypothermia