Ubiquinol as a Metabolic Resuscitator in Post-Cardiac Arrest

• Sponsor: Beth Israel Deaconess Medical Center (Other)
• Overall Status: Completed
• CT.gov ID: NCT02934555
• Collaborator: Kaneka Medical America LLC (Industry)
• Enrollment: 48
• Location: 1
• Arms: 2
• Duration (Months): 39
• Patients Per Site Per Month: 1.2

Study Details

Study Description

Brief Summary

To study the effects of ubiquinol as a "metabolic resuscitator" in post-cardiac arrest.

Condition or Disease	Intervention/Treatment	Phase
Cardiac Arrest	Drug: Ubiquinol; Dietary Supplement: Ensure	Phase 2

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 48 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Other
• Official Title: Ubiquinol as a Metabolic Resuscitator in Post-Cardiac Arrest
• Study Start Date: Mar 1, 2016
• Actual Primary Completion Date: May 25, 2019
• Actual Study Completion Date: Jun 2, 2019

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Control Patients in the control group will receive a liquid placebo, which is 50 mL of Ensure (a dietary supplement). This will be given every 12 hours for 7 days, until neurologic recovery, or until hospital discharge.	Dietary Supplement: Ensure; 50 mL Ensure
Experimental: Ubiquinol Patients in the experimental group will receive 300 mg of Ubiquinol in a liquid mixture. The liquid Ubiquinol will be mixed with 50 mL of Ensure (a dietary supplement) to ensure blinding. This will be given every 12 hours for 7 days, until neurologic recovery, or until hospital discharge.	Drug: Ubiquinol; 300 mg Ubiquinol (3 mL liquid Ubiquinol).; Other Names: CoQ10 ; Dietary Supplement: Ensure; 50 mL Ensure

Outcome Measures

Primary Outcome Measures

1. Coenzyme Q10 Plasma Levels [Up to 72 hours]

   Total (oxidized and reduced form) coenzyme Q10

Secondary Outcome Measures

1. Decreased Neurological Injury [Up to 72 hours]

   Neuron Specific Enolase levels

2. Cellular Oxygen Consumption [At 24 hours]

   Cellular (peripheral blood mononuclear cells) oxygen consumption measured with the XFe24 Extracellular Flux Analyzer

3. Global Oxygen Consumption [Up to 48 hours]

   VO2 measured using a Compact Anesthesia monitor

4. Mortality [At hospital discharge, an average of 14 days]

   In-hospital mortality

5. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts 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)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Beth Israel Deaconess Medical Center	Boston	Massachusetts	United States	02215

Sponsors and Collaborators

• Beth Israel Deaconess Medical Center
• Kaneka Medical America LLC

Investigators

• Principal Investigator: Michael W Donnino, MD, Beth Israel Deaconess Medical Center

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Dec 20, 2020

More Information

Publications

None provided.

• Responsible Party: Michael Donnino, MD, Beth Israel Deaconess Medical Center
• ClinicalTrials.gov Identifier: NCT02934555
• Other Study ID Numbers: 2015P000319
• First Posted: Oct 17, 2016
• Last Update Posted: Feb 15, 2021
• Last Verified: Jan 1, 2021

• Additional relevant MeSH terms: Heart Arrest

Study Results

Participant Flow

Arm/Group Title	Placebo	Ubiquinol
Arm/Group Description	50 mL of Ensure (a dietary supplement) every 12 hours for 7 days, until neurologic recovery, or until hospital discharge.	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.
Period Title: Overall Study
STARTED	23	25
COMPLETED	21	22
NOT COMPLETED	2	3

Baseline Characteristics

Arm/Group Title	Placebo	Ubiquinol	Total
Arm/Group Description	50 mL of Ensure (a dietary supplement) every 12 hours for 7 days, until neurologic recovery, or until hospital discharge.	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.	Total of all reporting groups
Overall Participants	23	25	48
Age (years) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [years]	68	60	62
Sex: Female, Male (Count of Participants)
Female	7 30.4%	7 28%	14 29.2%
Male	16 69.6%	18 72%	34 70.8%
Race/Ethnicity, Customized (Count of Participants)
White	12 52.2%	6 24%	18 37.5%
Other	11 47.8%	19 76%	30 62.5%
Number of Participants with Shock (Count of Participants)
Shock	14 60.9%	16 64%	30 62.5%
Non-shock	9 39.1%	9 36%	18 37.5%

Outcome Measures

1. Primary Outcome

Title	Coenzyme Q10 Plasma Levels
Description	Total (oxidized and reduced form) coenzyme Q10
Time Frame	Up to 72 hours

Outcome Measure Data

Analysis Population Description

Blood samples were not available on all participants at all time-points.

Arm/Group Title	Placebo	Ubiquinol
Arm/Group Description	50 mL of Ensure (a dietary supplement) every 12 hours for 7 days, until neurologic recovery, or until hospital discharge.	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.
Measure Participants	23	25
0 hours	185	207
24 hours	113	441
48 hours	148	615
72 hours	157	554

2. Secondary Outcome

Title	Decreased Neurological Injury
Description	Neuron Specific Enolase levels
Time Frame	Up to 72 hours

Outcome Measure Data

Analysis Population Description

Blood samples were not available on all participants at all time-points.

Arm/Group Title	Placebo	Ubiquinol
Arm/Group Description	50 mL of Ensure (a dietary supplement) every 12 hours for 7 days, until neurologic recovery, or until hospital discharge.	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.
Measure Participants	23	25
0 hours	7.6	9.2
24 hours	8.2	16.8
48 hours	5.3	12.6
72 hours	6.8	14.4

3. Secondary Outcome

Title	Cellular Oxygen Consumption
Description	Cellular (peripheral blood mononuclear cells) oxygen consumption measured with the XFe24 Extracellular Flux Analyzer
Time Frame	At 24 hours

Outcome Measure Data

Analysis Population Description

Cellular oxygen consumption was measured in a subset of the total cohort.

Arm/Group Title	Placebo	Ubiquinol
Arm/Group Description	50 mL of Ensure (a dietary supplement) every 12 hours for 7 days, until neurologic recovery, or until hospital discharge.	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.
Measure Participants	21	22
Basal OCR	7.6	6.5
Maximal OCR	20.7	18.0

4. Secondary Outcome

Title	Global Oxygen Consumption
Description	VO2 measured using a Compact Anesthesia monitor
Time Frame	Up to 48 hours

Outcome Measure Data

Analysis Population Description

Global oxygen consumption was measured in a subset of the total cohort.

Arm/Group Title	Placebo	Ubiquinol
Arm/Group Description	50 mL of Ensure (a dietary supplement) every 12 hours for 7 days, until neurologic recovery, or until hospital discharge.	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.
Measure Participants	18	14
12 hours	3.1	3.5
24 hours	3.2	3.5
48 hours	3.8	4.4

5. Secondary Outcome

Title	Mortality
Description	In-hospital mortality
Time Frame	At hospital discharge, an average of 14 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Ubiquinol
Arm/Group Description	50 mL of Ensure (a dietary supplement) every 12 hours for 7 days, until neurologic recovery, or until hospital discharge.	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.
Measure Participants	23	25
Count of Participants [Participants]	14 60.9%	15 60%

6. Secondary Outcome

Title	Number of Participants With Favorable Neurological Outcome
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Ubiquinol
Arm/Group Description	50 mL of Ensure (a dietary supplement) every 12 hours for 7 days, until neurologic recovery, or until hospital discharge.	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.
Measure Participants	23	25
Count of Participants [Participants]	8 34.8%	9 36%

Adverse Events

Time Frame	From enrolment until hospital discharge.
Arm/Group Title	Placebo		Ubiquinol
Arm/Group Description	50 mL of Ensure (a dietary supplement) every 12 hours for 7 days, until neurologic recovery, or until hospital discharge.		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.
All Cause Mortality
	Placebo		Ubiquinol
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	14/23 (60.9%)		15/25 (60%)
Serious Adverse Events
	Placebo		Ubiquinol
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/23 (0%)		0/25 (0%)
Other (Not Including Serious) Adverse Events
	Placebo		Ubiquinol
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/23 (0%)		0/25 (0%)

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.