Acute Ischemic Stroke
Conditions
Keywords
Stroke, Nonhemorrhagic, hypothermia
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.
Interventions
DRUGCaffeinol
Infusion of caffeinol (9mg/kg caffeine + 0.4g/kg ethanol) over 2 hours.
PROCEDUREhypothermia
External or internal cooling for 24 hours and rewarming over 12 hours.
Sponsors
The University of Texas Health Science Center, Houston
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
1. Age 18-80 years 2. Clinical presentation of acute ischemic stroke 3. Computed tomography (CT) scan compatible with acute ischemic stroke. 4. Time to caffeinol treatment \< 240 minutes from stroke onset. 5. Time to hypothermia initiation \< 300 minutes from stroke onset. 6. Presumed cortical location of stroke (must have at least on sign such as aphasia, neglect, visual field cut) 7. National Institutes of Health Stroke Scale (NIHSS) \> 8 at time of each treatment. 8. Tissue plasminogen activator (TPA) treated patients must meet all established criteria for TPA.
Exclusion criteria
1. Etiology other than ischemic stroke. 2. Item 1a on NIHSS \> 1 3. Signs/symptoms of subcortical, brainstem or cerebellar stroke. 4. Symptoms resolving or NIHSS \< 8 at time of each treatment. 5. NIHSS \> 20 if right hemisphere or \>25 if left hemisphere 6. Known alcoholic 7. Clinical or laboratory evidence of alcohol intoxication. 8. Historical evidence of exogenous caffeine exposure beyond daily consumption of coffee or soft drinks. 9. Known hematologic dyscrasias that affect thrombosis. 10. Comorbid conditions likely to complicate therapy: 1. End-stage cardiomyopathy 2. Uncompensated or clinically significant arrhythmia 3. Myopathy 4. Liver disease 5. History of pelvic or abdominal mass likely to compress inferior vena cava. 6. End-stage AIDS 7. History of clinically significant gastrointestinal (GI) bleeding 8. Impaired renal function with creatinine clearance, 50 ml/min 11. Intracerebral / intraventricular hemorrhage 12. Systolic blood pressure (SBP) \> 210 or \< 100; diastolic blood pressure (DBP) \> 100 or \< 50 mmHg 13. Severe coagulopathy 14. Pregnancy 15. Use of monoamine oxidase inhibitor (MAOI),serotonin-specific reuptake inhibitor (SSRI) or Tricyclic Antidepressants (TCA) within the preceding 2 weeks 16. Known history of epilepsy.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Symptomatic Intracerebral Hemorrhage | from pre-dosage to 90 day followup | 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) |
| Number of Participants With Catheter Related Complications During Hypothermia & Rewarming | over 36 hour period | 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. |
| Number of Participants With Cardiorespiratory Failure | every 30 minutes during hypothermia induction | The possibility of cardiorespiratory failure was monitored every 30 minutes during the 24 hour hypothermia period based on vitals signs and oxygen saturation. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Feasibility: Time Required to Reach the Target Core Temperature or Lowest Tolerated Temperature, Stability of Patient Temperature, Control of Rewarming, | rewarming over 12 hours until 36.5C has been achieved | Hypothermia will be maintained for 24 hours, afterward, the patient will be rewarmed, gradually, over 12 hours to 36.5C. |
| 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. | 90 days | 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. |
Countries
United States
Participant flow
Recruitment details
Patient/& or family was approached by one of the investigators in the Emergency Department in order to obtain informed consent.
Pre-assignment details
Open label pilot trial; Caffeinol Arm
Participants by arm
| Arm | Count |
|---|---|
| Caffeinol Caffeinol will be administered over a 2 hour infusion period. Dosage of caffeinol is based on on-going dose escalation trials and based on the patients weight. Currently the dosage is: ethanol 10% (0.4gm/kg) and caffeine 9 mg/kg. | 30 |
| Total | 30 |
Baseline characteristics
| Characteristic | Caffeinol |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 2 Participants |
| Age, Categorical Between 18 and 65 years | 28 Participants |
| Age Continuous | 54.7 years STANDARD_DEVIATION 15.6 |
| Region of Enrollment United States | 30 participants |
| Sex: Female, Male Female | 18 Participants |
| Sex: Female, Male Male | 12 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 17 / 30 |
| serious Total, serious adverse events | 9 / 30 |
Outcome results
Primary
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.
Time frame: every 30 minutes during hypothermia induction
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Caffeinol | Number of Participants With Cardiorespiratory Failure | 0 participants |
Primary
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.
Time frame: over 36 hour period
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Caffeinol | Number of Participants With Catheter Related Complications During Hypothermia & Rewarming | 0 participants |
Primary
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)
Time frame: from pre-dosage to 90 day followup
Population: Number of participants were determined by intention to treat. We did not use any imputation technique.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Caffeinol | Number of Participants With Symptomatic Intracerebral Hemorrhage | 0 participants |
Secondary
Achievement of Therapeutic Serum Ethanol and Caffeine Levels, and Amount of Sedation Needed to Suppress Shivering.
Time frame: rewarming over 12 hours until 36.5C has been achieved
Secondary
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.
Time frame: 90 days
Secondary
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.
Time frame: rewarming over 12 hours until 36.5C has been achieved