Cardiac Arrest
Conditions
Brief summary
To study the effects of ubiquinol as a metabolic resuscitator in post-cardiac arrest.
Detailed description
Cardiac arrest (CA) occurs in more than 400,000 patients in the United States each year with an estimated mortality of greater than 90%. The majority of patients who are resuscitated from CA will succumb to the neurologic morbidity associated with the post-CA syndrome and ischemic-reperfusion injury. Currently, there are no pharmacologic agents known to offer survival benefit or to prevent devastating neurologic injury in post-CA patients. A potential therapeutic target following ischemia-reperfusion injury is mitochondrial function in the injured cell and/or reduction of oxygen free radicals. Coenzyme Q10 (CoQ10) is an essential mitochondrial co-factor and free radical scavenger that has been proposed as a neuroprotective agent in various neurodegenerative disorders as well as a cardioprotective agent. CoQ10 have furthermore shown exciting preliminary results as a potential therapy in post-CA. In order to test the effects of ubiquinol as a metabolic resuscitator in post-CA patients and to provide additional preliminary data for a large-scale clinical trial, the investigators are conducting a randomized, double-blind, place-controlled trial of ubiquinol in post-CA patients.
Interventions
Sponsors
Kaneka Medical America LLC
Beth Israel Deaconess Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Adult (≥ 18 years) * Cardiac arrest defined by cessation of pulse requiring chest compressions * Not following commands after ROSC * Admission to the ICU * Naso/orogastric tube * Ability to receive enteral medication
Exclusion criteria
* Protected populations (pregnant women, prisoners, the intellectual disabled) * Current CoQ10 supplementation * Anticipated death within 24 hours * \> 12 hours from ROSC to estimated randomization * Jejunostomy tube (J-tube)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Coenzyme Q10 Plasma Levels | Up to 72 hours | Total (oxidized and reduced form) coenzyme Q10 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Decreased Neurological Injury | Up to 72 hours | Neuron Specific Enolase levels |
| Cellular Oxygen Consumption | At 24 hours | Cellular (peripheral blood mononuclear cells) oxygen consumption measured with the XFe24 Extracellular Flux Analyzer |
| Global Oxygen Consumption | Up to 48 hours | VO2 measured using a Compact Anesthesia monitor |
| Mortality | At hospital discharge, an average of 14 days | In-hospital mortality |
| Number of Participants With Favorable Neurological Outcome | At hospital discharge, an average of 14 days | Favorable Neurological Outcome as measured by the Cerebral Performance Category (CPC 1-2) score. A CPC score of 1 (mild or no neurological deficit) or 2 (moderate disability) was defined as a favorable neurological outcome. A CPC score of 3 (severe disability), 4 (vegetative state), or 5 (death) was defined as an unfavourable neurological outcome. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo 50 mL of Ensure (a dietary supplement) every 12 hours for 7 days, until neurologic recovery, or until hospital discharge. | 23 |
| Ubiquinol 300 mg of Ubiquinol mixed with 50 mL of Ensure (a dietary supplement) every 12 hours for 7 days, until neurologic recovery, or until hospital discharge. | 25 |
| Total | 48 |
Baseline characteristics
| Characteristic | Placebo | Ubiquinol | Total |
|---|---|---|---|
| Age, Continuous | 68 years | 60 years | 62 years |
| Number of Participants with Shock Non-shock | 9 Participants | 9 Participants | 18 Participants |
| Number of Participants with Shock Shock | 14 Participants | 16 Participants | 30 Participants |
| Race/Ethnicity, Customized Other | 11 Participants | 19 Participants | 30 Participants |
| Race/Ethnicity, Customized White | 12 Participants | 6 Participants | 18 Participants |
| Sex: Female, Male Female | 7 Participants | 7 Participants | 14 Participants |
| Sex: Female, Male Male | 16 Participants | 18 Participants | 34 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 14 / 23 | 15 / 25 |
| other Total, other adverse events | 0 / 23 | 0 / 25 |
| serious Total, serious adverse events | 0 / 23 | 0 / 25 |
Outcome results
Primary
Coenzyme Q10 Plasma Levels
Total (oxidized and reduced form) coenzyme Q10
Time frame: Up to 72 hours
Population: Blood samples were not available on all participants at all time-points.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Placebo | Coenzyme Q10 Plasma Levels | 0 hours | 185 ng/mL |
| Placebo | Coenzyme Q10 Plasma Levels | 24 hours | 113 ng/mL |
| Placebo | Coenzyme Q10 Plasma Levels | 48 hours | 148 ng/mL |
| Placebo | Coenzyme Q10 Plasma Levels | 72 hours | 157 ng/mL |
| Ubiquinol | Coenzyme Q10 Plasma Levels | 72 hours | 554 ng/mL |
| Ubiquinol | Coenzyme Q10 Plasma Levels | 0 hours | 207 ng/mL |
| Ubiquinol | Coenzyme Q10 Plasma Levels | 48 hours | 615 ng/mL |
| Ubiquinol | Coenzyme Q10 Plasma Levels | 24 hours | 441 ng/mL |
Secondary
Cellular Oxygen Consumption
Cellular (peripheral blood mononuclear cells) oxygen consumption measured with the XFe24 Extracellular Flux Analyzer
Time frame: At 24 hours
Population: Cellular oxygen consumption was measured in a subset of the total cohort.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Placebo | Cellular Oxygen Consumption | Basal OCR | 7.6 mL/min/mg |
| Placebo | Cellular Oxygen Consumption | Maximal OCR | 20.7 mL/min/mg |
| Ubiquinol | Cellular Oxygen Consumption | Basal OCR | 6.5 mL/min/mg |
| Ubiquinol | Cellular Oxygen Consumption | Maximal OCR | 18.0 mL/min/mg |
Secondary
Decreased Neurological Injury
Neuron Specific Enolase levels
Time frame: Up to 72 hours
Population: Blood samples were not available on all participants at all time-points.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Placebo | Decreased Neurological Injury | 0 hours | 7.6 ng/mL |
| Placebo | Decreased Neurological Injury | 24 hours | 8.2 ng/mL |
| Placebo | Decreased Neurological Injury | 48 hours | 5.3 ng/mL |
| Placebo | Decreased Neurological Injury | 72 hours | 6.8 ng/mL |
| Ubiquinol | Decreased Neurological Injury | 72 hours | 14.4 ng/mL |
| Ubiquinol | Decreased Neurological Injury | 0 hours | 9.2 ng/mL |
| Ubiquinol | Decreased Neurological Injury | 48 hours | 12.6 ng/mL |
| Ubiquinol | Decreased Neurological Injury | 24 hours | 16.8 ng/mL |
Secondary
Global Oxygen Consumption
VO2 measured using a Compact Anesthesia monitor
Time frame: Up to 48 hours
Population: Global oxygen consumption was measured in a subset of the total cohort.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Placebo | Global Oxygen Consumption | 24 hours | 3.2 mL/min/kg |
| Placebo | Global Oxygen Consumption | 48 hours | 3.8 mL/min/kg |
| Placebo | Global Oxygen Consumption | 12 hours | 3.1 mL/min/kg |
| Ubiquinol | Global Oxygen Consumption | 12 hours | 3.5 mL/min/kg |
| Ubiquinol | Global Oxygen Consumption | 24 hours | 3.5 mL/min/kg |
| Ubiquinol | Global Oxygen Consumption | 48 hours | 4.4 mL/min/kg |
Secondary
Mortality
In-hospital mortality
Time frame: At hospital discharge, an average of 14 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Mortality | 14 Participants |
| Ubiquinol | Mortality | 15 Participants |
Secondary
Number of Participants With Favorable Neurological Outcome
Favorable Neurological Outcome as measured by the Cerebral Performance Category (CPC 1-2) score. A CPC score of 1 (mild or no neurological deficit) or 2 (moderate disability) was defined as a favorable neurological outcome. A CPC score of 3 (severe disability), 4 (vegetative state), or 5 (death) was defined as an unfavourable neurological outcome.
Time frame: At hospital discharge, an average of 14 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Participants With Favorable Neurological Outcome | 8 Participants |
| Ubiquinol | Number of Participants With Favorable Neurological Outcome | 9 Participants |