Trial Outcomes & Findings for Caffeinol Hypothermia Protocol (NCT NCT00299416)

Last Updated: 2011-05-03

Results Overview

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)

Recruitment status

COMPLETED

Study phase

PHASE1/PHASE2

Target enrollment

30 participants

Primary outcome timeframe

from pre-dosage to 90 day followup

Results posted on

2011-05-03

Participant Flow

Patient/\& or family was approached by one of the investigators in the Emergency Department in order to obtain informed consent.

Open label pilot trial; Caffeinol Arm

Participant milestones

Participant milestones
Measure	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.
Overall Study STARTED	30
Overall Study COMPLETED	30
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Caffeinol Hypothermia Protocol

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Caffeinol n=30 Participants 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.
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	28 Participants n=5 Participants
Age, Categorical >=65 years	2 Participants n=5 Participants
Age Continuous	54.7 years STANDARD_DEVIATION 15.6 • n=5 Participants
Sex: Female, Male Female	18 Participants n=5 Participants
Sex: Female, Male Male	12 Participants n=5 Participants
Region of Enrollment United States	30 participants n=5 Participants

PRIMARY outcome

Timeframe: from pre-dosage to 90 day followup

Population: Number of participants were determined by intention to treat. We did not use any imputation technique.

Outcome measures

Outcome measures
Measure	Caffeinol n=30 Participants 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.
Number of Participants With Symptomatic Intracerebral Hemorrhage	0 participants

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Caffeinol n=30 Participants 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.
Number of Participants With Catheter Related Complications During Hypothermia & Rewarming	0 participants

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Caffeinol n=30 Participants 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.
Number of Participants With Cardiorespiratory Failure	0 participants

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: rewarming over 12 hours until 36.5C has been achieved

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome data not reported

Adverse Events

Caffeinol

Serious events: 9 serious events

Other events: 17 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Caffeinol n=30 participants at risk 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.
Nervous system disorders Death	10.0% 3/30 • Adverse event data was collected over the duration of the study (2003-2009)
Nervous system disorders Neuroworsening	13.3% 4/30 • Adverse event data was collected over the duration of the study (2003-2009)
Hepatobiliary disorders Cholecysitits	3.3% 1/30 • Adverse event data was collected over the duration of the study (2003-2009)
Respiratory, thoracic and mediastinal disorders Reduced respiratory drive	3.3% 1/30 • Adverse event data was collected over the duration of the study (2003-2009)
Nervous system disorders Parenchymal hemorrhage	13.3% 4/30 • Adverse event data was collected over the duration of the study (2003-2009)
Blood and lymphatic system disorders Thrombotic thrombocytopenia	3.3% 1/30 • Adverse event data was collected over the duration of the study (2003-2009)

Other adverse events

Other adverse events
Measure	Caffeinol n=30 participants at risk 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.
Infections and infestations Infection	20.0% 6/30 • Adverse event data was collected over the duration of the study (2003-2009)
Blood and lymphatic system disorders Low Hgb/ Hct	6.7% 2/30 • Adverse event data was collected over the duration of the study (2003-2009)
Blood and lymphatic system disorders Abnormal Labs (chem.)	10.0% 3/30 • Adverse event data was collected over the duration of the study (2003-2009)
Cardiac disorders Arrhythmia	10.0% 3/30 • Adverse event data was collected over the duration of the study (2003-2009)
Respiratory, thoracic and mediastinal disorders Pleural Effusion	6.7% 2/30 • Adverse event data was collected over the duration of the study (2003-2009)
Surgical and medical procedures Sedation	13.3% 4/30 • Adverse event data was collected over the duration of the study (2003-2009)
Cardiac disorders Elevated CK	33.3% 10/30 • Adverse event data was collected over the duration of the study (2003-2009)
Gastrointestinal disorders Elevated Amylase	6.7% 2/30 • Adverse event data was collected over the duration of the study (2003-2009)
Surgical and medical procedures Device failure	13.3% 4/30 • Adverse event data was collected over the duration of the study (2003-2009)
Nervous system disorders Asymptomatic hemorrhagic transformation	23.3% 7/30 • Adverse event data was collected over the duration of the study (2003-2009)
Blood and lymphatic system disorders Elevated WBC	6.7% 2/30 • Adverse event data was collected over the duration of the study (2003-2009)
Respiratory, thoracic and mediastinal disorders Respiratory distress	6.7% 2/30 • Adverse event data was collected over the duration of the study (2003-2009)

Additional Information

James C. Grotta, MD

UT-Houston Health Science Center, Department of Neurology

Phone: 713-500-7088

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place