Cardiac Arrest, Sudden Cardiac Arrest
Conditions
Keywords
Cardiac Arrest, Post Cardiac Arrest, CoQ10, Ubiquinone, Post Arrest
Brief summary
Specific Aim #1: To determine if levels of CoQ10 are low post-cardiac arrest (CA). We will perform a prospective trial with the primary endpoint of describing the prevalence of low serum CoQ10 levels. Specific Aim #2: To determine if CoQ10 levels in post-CA patients can be increased with the administration of exogenous CoQ10.. We will perform a randomized control trial (RCT) of post-CA patients with the secondary endpoint of comparing CoQ10 levels among those randomized to CoQ10 supplementation vs placebo.
Detailed description
Cardiac arrest (CA) occurs in nearly 350,000 patients in the U.S. each year with an estimated mortality of 60% in those surviving the initial arrest. Moreover, the overall prognosis for survivors is often limited by neurologic injury. Two randomized control trials (RCTs) have demonstrated that therapeutic hypothermia (TH) after CA improves survival and reduces neurologic morbidity. As a result of these studies, TH has become the standard of care in post-CA patients. The mechanism of action for TH is hypothesized to be a reduction in cerebral oxygen consumption that occurs following an ischemia-reperfusion injury. Another similar potential target following ischemia-reperfusion injury is mitochondrial function in the injured brain cells and attenuation of potentially damaging oxygen-free radicals. Specifically, optimizing mitochondrial function and reducing oxygen free radicals may enhance cellular function and mitigate cellular injury thereby leading to improved neurologic outcomes. Coenzyme Q10 (CoQ10) is an essential mitochondrial co-factor and free radical scavenger that has been found to have neuroprotective effects in various neurodegenerative disorders such as Parkinson's disease and Huntington's disease. Whether CoQ10 can provide neuroprotection in acute ischemia-reperfusion injury remains less clear, but has been recognized by the American Heart Association as a potentially promising neuroprotective agent. We hypothesize that the administration of exogenous CoQ10 will raise serum concentrations of CoQ10 and as such may mitigate the adverse effects of the post-CA ischemia-reperfusion injury on the brain by optimizing mitochondrial function and reducing oxygen-free radicals. We support this hypothesis by the following: 1. Ischemia-reperfusion injury disrupts normal mitochondrial function and increases O2 free radicals. 2. CoQ10 has been found to attenuate the effects of ischemia-reperfusion injury through optimizing mitochondrial function and mitigation of cellular apoptosis. 3. CoQ10 has neuroprotective effects in other neurodegenerative disorders. 4. Our group has unpublished preliminary data showing low CoQ10 levels in a majority of patients with septic shock, and that lower CoQ10 levels are significantly associated with multiple markers of the inflammatory cascade. 5. A pilot human trial in post-CA patients demonstrated a reduction in mortality and trend toward reduction in neurologic morbidity. To test our hypothesis, we propose the following pilot study as proof of concept in preparation for a larger multicenter trial powered toward neurologic outcome and mortality. This pilot study will allow for a more informed power analysis for a larger trial, provide proof of concept for enrollment and administration of therapy, examine the time-frame for drug absorption into serum, and evaluate for tolerability.
Interventions
DRUGCoenzyme Q10
Patients will receive CoQ10 200mg three times per day for 7 days, until return to baseline neurologic status, or until death/discharge (whichever comes first). CoQ10 will be given through pre-existing NG or OG tube, and mixed with 20 ml of chocolate Ensure so as to blind investigators and staff.
DIETARY_SUPPLEMENTPlacebo
Patients will be given Chocolate Ensure via NG/ OG 3x daily as a placebo.
Sponsors
Beth Israel Deaconess Medical Center
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
1. Adult patients (age \> 18 years) 2. Comatose after CA with subsequent return of spontaneous circulation
Exclusion criteria
1. Comatose status prior to CA 2. CoQ10 therapy within one month prior to CA 3. Pregnancy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Prevalence of Low Serum CoQ10 Levels in Cardiac Arrest Patients | Baseline | The primary outcome will be describing the prevalence of low serum CoQ10 levels compared to standard laboratory control values. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Comparison of Serum CoQ10 Levels Randomized to Supplementation vs. Placebo | 1 year | The secondary outcome will be to compare serum CoQ10 levels among those post-arrest patients randomized to CoQ10 supplementation vs placebo. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| CoenzymeQ10 Patients will receive CoenzymeQ10 200mg three times per day for 7 days, until return to baseline neurologic status, or until death/discharge (whichever comes first). CoQ10 will be given through pre-existing NG or OG tube, and mixed with 20 ml of chocolate Ensure so as to blind investigators and staff.
Coenzyme Q10: Patients will receive CoQ10 200mg three times per day for 7 days, until return to baseline neurologic status, or until death/discharge (whichever comes first). CoQ10 will be given through pre-existing NG or OG tube, and mixed with 20 ml of chocolate Ensure so as to blind investigators and staff. | 5 |
| Placebo Patients will receive 20 ml chocolate Ensure (as a placebo) three times per day for 7 days, until return to baseline neurologic status, or until death/discharge (whichever comes first). Placebo will be given through pre-existing NG or OG tube.
Placebo: Patients will be given Chocolate Ensure via NG/ OG 3x daily as a placebo. | 5 |
| Total | 10 |
Baseline characteristics
| Characteristic | Total | CoenzymeQ10 | Placebo |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 1 Participants | 1 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 9 Participants | 4 Participants | 5 Participants |
| Sex: Female, Male Female | 3 Participants | 1 Participants | 2 Participants |
| Sex: Female, Male Male | 7 Participants | 4 Participants | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 1 / 5 | 0 / 5 |
| serious Total, serious adverse events | 2 / 5 | 2 / 5 |
Outcome results
Primary
Prevalence of Low Serum CoQ10 Levels in Cardiac Arrest Patients
The primary outcome will be describing the prevalence of low serum CoQ10 levels compared to standard laboratory control values.
Time frame: Baseline
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CoenzymeQ10 | Prevalence of Low Serum CoQ10 Levels in Cardiac Arrest Patients | 0.706 ug/mL | Standard Deviation 0.290137 |
| Placebo | Prevalence of Low Serum CoQ10 Levels in Cardiac Arrest Patients | 0.66 ug/mL | Standard Deviation 0.267955 |
Secondary
Comparison of Serum CoQ10 Levels Randomized to Supplementation vs. Placebo
The secondary outcome will be to compare serum CoQ10 levels among those post-arrest patients randomized to CoQ10 supplementation vs placebo.
Time frame: 1 year
Population: This data was not collected when the study was performed