Anoxia, Coma, Heart Arrest
Conditions
Keywords
heart arrest, resuscitation, seizures, hypothermia, induced, Amantadine
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.
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.
Interventions
DRUGAmantadine
100mg twice per day for 7 days at 0600 and 1200
DRUGPlacebo
Placebo comparator
Sponsors
American Heart Association
Jon Rittenberger, MD
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| Time to Awakening | up to 28 days | Defined as the time from enrollment to awakening |
| 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 |
| Nausea or Vomiting | during study drug administration (7 days) | nausea requiring antiemetic medications or clinical vomiting |
| 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 |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo Placebo medication administered at 0600 and 1200 via mouth, gastric tube or duo-tube.
Placebo: Placebo comparator | 7 |
| Amantadine 100mg Amantadine administered at 0600 and 1200 via mouth, gastric tube or duo-tube.
Amantadine: 100mg BID for 7 days at 0600 and 1200 | 7 |
| Total | 14 |
Baseline characteristics
| Characteristic | Placebo | Total | Amantadine |
|---|---|---|---|
| Age, Continuous | 55 years STANDARD_DEVIATION 9 | 55 years STANDARD_DEVIATION 13 | 54 years STANDARD_DEVIATION 16 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 6 Participants | 13 Participants | 7 Participants |
| Region of Enrollment United States | 7 participants | 14 participants | 7 participants |
| Sex: Female, Male Female | 3 Participants | 4 Participants | 1 Participants |
| Sex: Female, Male Male | 4 Participants | 10 Participants | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 4 / 7 | 3 / 7 |
| other Total, other adverse events | 1 / 7 | 2 / 7 |
| serious Total, serious adverse events | 0 / 7 | 0 / 7 |
Outcome results
Primary
Rate of Awakening (Number of Patients Who Are Able to Follow Commands)
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
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Amantadine | Rate of Awakening (Number of Patients Who Are Able to Follow Commands) | 2 Participants |
| Placebo | Rate of Awakening (Number of Patients Who Are Able to Follow Commands) | 2 Participants |
Secondary
Nausea or Vomiting
nausea requiring antiemetic medications or clinical vomiting
Time frame: during study drug administration (7 days)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Amantadine | Nausea or Vomiting | 0 Participants |
| Placebo | Nausea or Vomiting | 0 Participants |
Secondary
Number of Participants With Severe or Intracranial Bleeding
Bleeding that does not stop with direct pressure, requires transfusion, or occurs in the intracranial vault
Time frame: 28 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Amantadine | Number of Participants With Severe or Intracranial Bleeding | 0 Participants |
| Placebo | Number of Participants With Severe or Intracranial Bleeding | 0 Participants |
Secondary
Seizures (Number of Patients Who Experience Seizures as Detected by EEG Monitoring With or Without Clinical Correlate)
detected by EEG monitoring with or without clinical correlate
Time frame: during study drug administration (7 days)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Amantadine | Seizures (Number of Patients Who Experience Seizures as Detected by EEG Monitoring With or Without Clinical Correlate) | 0 Participants |
| Placebo | Seizures (Number of Patients Who Experience Seizures as Detected by EEG Monitoring With or Without Clinical Correlate) | 2 Participants |
Secondary
Time to Awakening
Defined as the time from enrollment to awakening
Time frame: up to 28 days
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Amantadine | Time to Awakening | 4 days |
| Placebo | Time to Awakening | 8 days |