AWAKE: Amantadine to Speed Awakening After Cardiac Arrest

• Sponsor: Jon Rittenberger, MD (Other)
• Overall Status: Completed
• CT.gov ID: NCT02486211
• Collaborator: American Heart Association (Other)
• Enrollment: 14
• Locations: 4
• Arms: 2
• Duration (Months): 33.9
• Patients Per Site: 3.5
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

This study evaluates if amantadine will increase the rate of awakening in patients resuscitated from cardiac arrest but comatose (not following commands) after their resuscitation. Half of the participants will receive amantadine and the other will receive placebo.

Condition or Disease	Intervention/Treatment	Phase
Coma; Heart Arrest; Anoxia	Drug: Amantadine; Drug: Placebo	Phase 2

Detailed Description

Amantadine has been used to help patients awaken following traumatic brain injury, but it has not been studied in patients with anoxic brain injury.

Amantadine is a dopamine agonist and may help with stimulating the brain to awaken. The investigators will randomize subjects who remain comatose 72 hours following resuscitation from cardiac arrest to either amantadine or placebo. They will be treated with either amantadine or placebo for 7 days.

Study Design

• Study Type: Interventional
• Actual Enrollment: 14 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Amantadine to Speed Awakening After Cardiac Arrest
• Study Start Date: Sep 1, 2015
• Actual Primary Completion Date: Jun 30, 2018
• Actual Study Completion Date: Jun 30, 2018

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Placebo Placebo medication administered at 0600 and 1200 via mouth, gastric tube or duo-tube.	Drug: Placebo; Placebo comparator
Experimental: Amantadine 100mg Amantadine administered at 0600 and 1200 via mouth, gastric tube or duo-tube.	Drug: Amantadine; 100mg twice per day for 7 days at 0600 and 1200; Other Names: Symmetrel

Outcome Measures

Primary Outcome Measures

1. Rate of Awakening (Number of Patients Who Are Able to Follow Commands) [up to 28 days]

   Defined as the ability to follow commands (i.e. "wiggle your toes" "open your eyes" "squeeze my fingers". This corresponds to a Full Outline of Unresponsiveness motor score of 4. FOUR (full outline of unresponsiveness) measures the following: Eye Response, Motor Response, Brainstem Reflexes, and Respirations.

Secondary Outcome Measures

1. Time to Awakening [up to 28 days]

   Defined as the time from enrollment to awakening

2. Seizures (Number of Patients Who Experience Seizures as Detected by EEG Monitoring With or Without Clinical Correlate) [during study drug administration (7 days)]

   detected by EEG monitoring with or without clinical correlate

3. Nausea or Vomiting [during study drug administration (7 days)]

   nausea requiring antiemetic medications or clinical vomiting

4. Number of Participants With Severe or Intracranial Bleeding [28 days]

   Bleeding that does not stop with direct pressure, requires transfusion, or occurs in the intracranial vault

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Non traumatic cardiac arrest

• Age 18 and older

• Defibrillation and/or chest compressions by healthcare providers

• Return of spontaneous circulation

Exclusion Criteria:

• Written do not attempt resuscitation (DNAR) reported to providers before randomization

• Known prisoner or pregnancy

• Lack of motor response to pain and absent N20 response on somatosensory evoked potentials prior to randomization

• Initial CT demonstrating brain edema (defined as grey white ratio <1.2)

• Presence of malignant pattern on EEG at time of randomization

• Next of kin unwilling to provide supportive care for at least one week after enrollment

• Presently using other dopaminergic agent

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Main Medical Center	Portland	Maine	United States	04101
2	Beth Israel Deacconness	Boston	Massachusetts	United States	02215
3	UPMC Presbyterian Hospital	Pittsburgh	Pennsylvania	United States	15216
4	UPMC Mercy Hospital	Pittsburgh	Pennsylvania	United States	15219

Sponsors and Collaborators

• Jon Rittenberger, MD
• American Heart Association

Investigators

• Principal Investigator: Jon C Rittenberger, MD, University of Pittsburgh

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Jun 28, 2019

More Information

Publications

None provided.

• Responsible Party: Jon Rittenberger, MD, Associate Professor of Emergency Medicine, University of Pittsburgh
• ClinicalTrials.gov Identifier: NCT02486211
• Other Study ID Numbers: 15GRNT25680021
• First Posted: Jul 1, 2015
• Last Update Posted: Dec 4, 2019
• Last Verified: Nov 1, 2019

• Keywords provided by Jon Rittenberger, MD, Associate Professor of Emergency Medicine, University of Pittsburgh: heart arrest; resuscitation; seizures; hypothermia, induced; Amantadine
• Additional relevant MeSH terms: Heart Arrest; Amantadine

Study Results

Participant Flow

Arm/Group Title	Amantadine	Placebo
Arm/Group Description	100mg Amantadine administered at 0600 and 1200 via mouth, gastric tube or duo-tube. Amantadine: 100mg twice per day for 7 days at 0600 and 1200	Placebo medication administered at 0600 and 1200 via mouth, gastric tube or duo-tube. Placebo: Placebo comparator
Period Title: Overall Study
STARTED	7	7
COMPLETED	6	7
NOT COMPLETED	1	0

Baseline Characteristics

Arm/Group Title	Placebo	Amantadine	Total
Arm/Group Description	Placebo medication administered at 0600 and 1200 via mouth, gastric tube or duo-tube. Placebo: Placebo comparator	100mg Amantadine administered at 0600 and 1200 via mouth, gastric tube or duo-tube. Amantadine: 100mg BID for 7 days at 0600 and 1200	Total of all reporting groups
Overall Participants	7	7	14
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	55 (9)	54 (16)	55 (13)
Sex: Female, Male (Count of Participants)
Female	3 42.9%	1 14.3%	4 28.6%
Male	4 57.1%	6 85.7%	10 71.4%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	1 14.3%	0 0%	1 7.1%
White	6 85.7%	7 100%	13 92.9%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	7 100%	7 100%	14 100%

Outcome Measures

1. Primary Outcome

Title	Rate of Awakening (Number of Patients Who Are Able to Follow Commands)
Description	Defined as the ability to follow commands (i.e. "wiggle your toes" "open your eyes" "squeeze my fingers". This corresponds to a Full Outline of Unresponsiveness motor score of 4. FOUR (full outline of unresponsiveness) measures the following: Eye Response, Motor Response, Brainstem Reflexes, and Respirations.
Time Frame	up to 28 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Amantadine	Placebo
Arm/Group Description	100mg Amantadine administered at 0600 and 1200 via mouth, gastric tube or duo-tube. Amantadine: 100mg twice per day for 7 days at 0600 and 1200	Placebo medication administered at 0600 and 1200 via mouth, gastric tube or duo-tube. Placebo: Placebo comparator
Measure Participants	7	7
Count of Participants [Participants]	2 28.6%	2 28.6%

2. Secondary Outcome

Title	Time to Awakening
Description	Defined as the time from enrollment to awakening
Time Frame	up to 28 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Amantadine	Placebo
Arm/Group Description	100mg Amantadine administered at 0600 and 1200 via mouth, gastric tube or duo-tube. Amantadine: 100mg BID for 7 days at 0600 and 1200	Placebo medication administered at 0600 and 1200 via mouth, gastric tube or duo-tube. Placebo: Placebo comparator
Measure Participants	2	2
Median (Inter-Quartile Range) [days]	4	8

3. Secondary Outcome

Title	Seizures (Number of Patients Who Experience Seizures as Detected by EEG Monitoring With or Without Clinical Correlate)
Description	detected by EEG monitoring with or without clinical correlate
Time Frame	during study drug administration (7 days)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Amantadine	Placebo
Arm/Group Description	100mg Amantadine administered at 0600 and 1200 via mouth, gastric tube or duo-tube. Amantadine: 100mg BID for 7 days at 0600 and 1200	Placebo medication administered at 0600 and 1200 via mouth, gastric tube or duo-tube. Placebo: Placebo comparator
Measure Participants	7	7
Count of Participants [Participants]	0 0%	2 28.6%

4. Secondary Outcome

Title	Nausea or Vomiting
Description	nausea requiring antiemetic medications or clinical vomiting
Time Frame	during study drug administration (7 days)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Amantadine	Placebo
Arm/Group Description	100mg Amantadine administered at 0600 and 1200 via mouth, gastric tube or duo-tube. Amantadine: 100mg BID for 7 days at 0600 and 1200	Placebo medication administered at 0600 and 1200 via mouth, gastric tube or duo-tube. Placebo: Placebo comparator
Measure Participants	7	7
Count of Participants [Participants]	0 0%	0 0%

5. Secondary Outcome

Title	Number of Participants With Severe or Intracranial Bleeding
Description	Bleeding that does not stop with direct pressure, requires transfusion, or occurs in the intracranial vault
Time Frame	28 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Amantadine	Placebo
Arm/Group Description	100mg Amantadine administered at 0600 and 1200 via mouth, gastric tube or duo-tube. Amantadine: 100mg BID for 7 days at 0600 and 1200	Placebo medication administered at 0600 and 1200 via mouth, gastric tube or duo-tube. Placebo: Placebo comparator
Measure Participants	7	7
Count of Participants [Participants]	0 0%	0 0%

Adverse Events

Time Frame	7 days
Arm/Group Title	Amantadine		Placebo
Arm/Group Description	100mg Amantadine administered at 0600 and 1200 via mouth, gastric tube or duo-tube. Amantadine: 100mg BID for 7 days at 0600 and 1200		Placebo medication administered at 0600 and 1200 via mouth, gastric tube or duo-tube. Placebo: Placebo comparator
All Cause Mortality
	Amantadine		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/7 (57.1%)		3/7 (42.9%)
Serious Adverse Events
	Amantadine		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/7 (0%)		0/7 (0%)
Other (Not Including Serious) Adverse Events
	Amantadine		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/7 (14.3%)		2/7 (28.6%)
Gastrointestinal disorders
Tongue swelling	1/7 (14.3%)	1	0/7 (0%)	0
Nervous system disorders
seizure	0/7 (0%)	0	2/7 (28.6%)	2

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.