Trial Outcomes & Findings for Custodiol-HTK (Histidine-tryptophan-ketoglutarate) Solution as a Cardioplegic Agent (NCT NCT01681095)

NCT ID: NCT01681095

Last Updated: 2019-08-06

Results Overview

Creatine phosphokinase MB isoenzyme (CK-MB) difference from baseline 7 hours post surgery

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 110 participants
• Primary outcome timeframe: Baseline and 7 hours post surgery
• Results posted on: 2019-08-06

Participant Flow

Participant milestones

Measure	Cardioplegia: Custodiol HTK Solution Custodiol HTK (histidine-tryptophan-ketoglutarate) cardioplegia: One liter of HTK solution (Custodiol; Koehler Chemi, Alsbach-Haenlien, Germany) contains the following components: 15 mmol/L sodium chloride, 9 mmol/L potassium chloride, 4 mmol/L magnesium chloride, 18 mmol/L histidine hydrochloride, 180 mmol/L histidine, 2 mmol/L tryptophan, 30 mmol/L mannitol, 0.015 mmol/L calcium chloride, 1 mmol/L potassium hydrogen 2-ketoglutarate, osmolarity 310 mOsm/kg, pH 7.02-7.20. Custodiol-HTK was delivered to establish and maintain cardiac arrest. After cross-clamping of the aorta approximately 1-2 L of Custodiol-HTK was infused into the ascending aorta over 6-8 minutes. Additional doses of 100-200 ml were administered as needed. Custodiol-HTK was delivered at a temperature of 4°C - 10°C.	Cold Blood Cardioplegia Cold Blood Cardioplegia: One liter of cold blood cardioplegic solution, mixed at a ratio of 4:1 per Beaumont standard of care (blood /cardioplegic solution), contains the following in a 500 cc bag of D5W (dextrose 5% in water): 50meq/L potassium chloride, 37.5 meq/L sodium bicarbonate and 7.5 meq/L magnesium sulfate. After cross-clamping the aorta, at least 1000 mL of a 4:1 mixture of cold blood: cold crystalloid was administered at a pressure of 300 mmHg or less via a twin roller pump. Every 20 minutes an additional \> 200 mL was administered as needed. The cardioplegic solution was delivered at a temperature of 4°C - 8°C.
Overall Study STARTED	55	55
Overall Study COMPLETED	55	55
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Custodiol-HTK (Histidine-tryptophan-ketoglutarate) Solution as a Cardioplegic Agent

Baseline characteristics by cohort

Measure	Standard Cold Blood Cardioplegia n=55 Participants 55 participants were randomized to Standard cold blood cardioplegia. Cold Blood Cardioplegia: One liter of cold blood cardioplegic solution, mixed at a ratio of 4:1 per Beaumont standard of care (blood /cardioplegic solution), contains the following in a 500 cc bag of D5W (dextrose 5% in water): 50meq/L potassium chloride, 37.5 meq/L sodium bicarbonate and 7.5 meq/L magnesium sulfate. After cross-clamping the aorta, at least 1000 mL of a 4:1 mixture of cold blood: cold crystalloid was administered at a pressure of 300 mmHg or less via a twin roller pump. Every 20 minutes an additional \> 200 mL was administered as needed. The cardioplegic solution was delivered at a temperature of 4°C - 8°C.	Custiodiol HTK n=55 Participants 55 participants were randomized to Custodiol HTK. Custodiol HTK (histidine-tryptophan-ketoglutarate) cardioplegia: One liter of HTK solution (Custodiol; Koehler Chemi, Alsbach-Haenlien, Germany) contains the following components: 15 mmol/L sodium chloride, 9 mmol/L potassium chloride, 4 mmol/L magnesium chloride, 18 mmol/L histidine hydrochloride, 180 mmol/L histidine, 2 mmol/L tryptophan, 30 mmol/L mannitol, 0.015 mmol/L calcium chloride, 1 mmol/L potassium hydrogen 2-ketoglutarate, osmolarity 310 mOsm/kg, pH 7.02-7.20. Custodiol-HTK was delivered to establish and maintain cardiac arrest. After cross-clamping of the aorta approximately 1-2 L of Custodiol-HTK was infused into the ascending aorta over 6-8 minutes. Additional doses of 100-200 ml were administered as needed. Custodiol-HTK was delivered at a temperature of 4°C - 10°C.	Total n=110 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	23 Participants n=5 Participants	23 Participants n=7 Participants	46 Participants n=5 Participants
Age, Categorical >=65 years	32 Participants n=5 Participants	32 Participants n=7 Participants	64 Participants n=5 Participants
Age, Continuous	70 years STANDARD_DEVIATION 11 • n=5 Participants	63 years STANDARD_DEVIATION 13 • n=7 Participants	66 years STANDARD_DEVIATION 12 • n=5 Participants
Sex: Female, Male Female	20 Participants n=5 Participants	26 Participants n=7 Participants	46 Participants n=5 Participants
Sex: Female, Male Male	35 Participants n=5 Participants	29 Participants n=7 Participants	64 Participants n=5 Participants
Region of Enrollment United States	55 participants n=5 Participants	55 participants n=7 Participants	110 participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline and 7 hours post surgery

Population: Patients for which both baseline and 7 hours post surgery values were available

Creatine phosphokinase MB isoenzyme (CK-MB) difference from baseline 7 hours post surgery

Outcome measures

Measure	Cardioplegia: Custodiol HTK Solution n=40 Participants Custodiol HTK (histidine-tryptophan-ketoglutarate) cardioplegia: One liter of HTK solution (Custodiol; Koehler Chemi, Alsbach-Haenlien, Germany) contains the following components: 15 mmol/L sodium chloride, 9 mmol/L potassium chloride, 4 mmol/L magnesium chloride, 18 mmol/L histidine hydrochloride, 180 mmol/L histidine, 2 mmol/L tryptophan, 30 mmol/L mannitol, 0.015 mmol/L calcium chloride, 1 mmol/L potassium hydrogen 2-ketoglutarate, osmolarity 310 mOsm/kg, pH 7.02-7.20. Custodiol-HTK was delivered to establish and maintain cardiac arrest. After cross-clamping of the aorta approximately 1-2 L of Custodiol-HTK was infused into the ascending aorta over 6-8 minutes. Additional doses of 100-200 ml were administered as needed. Custodiol-HTK was delivered at a temperature of 4°C - 10°C.	Cold Blood Cardioplegia n=38 Participants Cold Blood Cardioplegia: One liter of cold blood cardioplegic solution, mixed at a ratio of 4:1 per Beaumont standard of care (blood /cardioplegic solution), contains the following in a 500 cc bag of D5W (dextrose 5% in water): 50meq/L potassium chloride, 37.5 meq/L sodium bicarbonate and 7.5 meq/L magnesium sulfate. After cross-clamping the aorta, at least 1000 mL of a 4:1 mixture of cold blood: cold crystalloid was administered at a pressure of 300 mmHg or less via a twin roller pump. Every 20 minutes an additional \> 200 mL was administered as needed. The cardioplegic solution was delivered at a temperature of 4°C - 8°C.
Change in Creatine Phosphokinase-MB Isoenzyme (CK-MB)	18.8 ng/mL Interval 12.5 to 24.0	22.2 ng/mL Interval 15.0 to 51.0

PRIMARY outcome

Timeframe: Baseline and 7 hours post surgery

Troponin I values, difference from baseline 7 hours post surgery

Outcome measures

Measure	Cardioplegia: Custodiol HTK Solution n=55 Participants Custodiol HTK (histidine-tryptophan-ketoglutarate) cardioplegia: One liter of HTK solution (Custodiol; Koehler Chemi, Alsbach-Haenlien, Germany) contains the following components: 15 mmol/L sodium chloride, 9 mmol/L potassium chloride, 4 mmol/L magnesium chloride, 18 mmol/L histidine hydrochloride, 180 mmol/L histidine, 2 mmol/L tryptophan, 30 mmol/L mannitol, 0.015 mmol/L calcium chloride, 1 mmol/L potassium hydrogen 2-ketoglutarate, osmolarity 310 mOsm/kg, pH 7.02-7.20. Custodiol-HTK was delivered to establish and maintain cardiac arrest. After cross-clamping of the aorta approximately 1-2 L of Custodiol-HTK was infused into the ascending aorta over 6-8 minutes. Additional doses of 100-200 ml were administered as needed. Custodiol-HTK was delivered at a temperature of 4°C - 10°C.	Cold Blood Cardioplegia n=55 Participants Cold Blood Cardioplegia: One liter of cold blood cardioplegic solution, mixed at a ratio of 4:1 per Beaumont standard of care (blood /cardioplegic solution), contains the following in a 500 cc bag of D5W (dextrose 5% in water): 50meq/L potassium chloride, 37.5 meq/L sodium bicarbonate and 7.5 meq/L magnesium sulfate. After cross-clamping the aorta, at least 1000 mL of a 4:1 mixture of cold blood: cold crystalloid was administered at a pressure of 300 mmHg or less via a twin roller pump. Every 20 minutes an additional \> 200 mL was administered as needed. The cardioplegic solution was delivered at a temperature of 4°C - 8°C.
Change in Troponin I	9.65 ng/mL Interval 5.47 to 16.0	10.15 ng/mL Interval 6.04 to 19.97

PRIMARY outcome

Timeframe: Baseline and 24 hours post surgery

Population: patients for whom both preoperative and 24 hour LV ejection fractions were obtained

LV ejection fraction by TTE, difference from baseline at 24 hours post surgery

Outcome measures

Measure	Cardioplegia: Custodiol HTK Solution n=51 Participants Custodiol HTK (histidine-tryptophan-ketoglutarate) cardioplegia: One liter of HTK solution (Custodiol; Koehler Chemi, Alsbach-Haenlien, Germany) contains the following components: 15 mmol/L sodium chloride, 9 mmol/L potassium chloride, 4 mmol/L magnesium chloride, 18 mmol/L histidine hydrochloride, 180 mmol/L histidine, 2 mmol/L tryptophan, 30 mmol/L mannitol, 0.015 mmol/L calcium chloride, 1 mmol/L potassium hydrogen 2-ketoglutarate, osmolarity 310 mOsm/kg, pH 7.02-7.20. Custodiol-HTK was delivered to establish and maintain cardiac arrest. After cross-clamping of the aorta approximately 1-2 L of Custodiol-HTK was infused into the ascending aorta over 6-8 minutes. Additional doses of 100-200 ml were administered as needed. Custodiol-HTK was delivered at a temperature of 4°C - 10°C.	Cold Blood Cardioplegia n=51 Participants Cold Blood Cardioplegia: One liter of cold blood cardioplegic solution, mixed at a ratio of 4:1 per Beaumont standard of care (blood /cardioplegic solution), contains the following in a 500 cc bag of D5W (dextrose 5% in water): 50meq/L potassium chloride, 37.5 meq/L sodium bicarbonate and 7.5 meq/L magnesium sulfate. After cross-clamping the aorta, at least 1000 mL of a 4:1 mixture of cold blood: cold crystalloid was administered at a pressure of 300 mmHg or less via a twin roller pump. Every 20 minutes an additional \> 200 mL was administered as needed. The cardioplegic solution was delivered at a temperature of 4°C - 8°C.
Changes in Left Ventricular (LV) Ejection Fraction (EF) by Transthoracic Echocardiogram (TTE)	-0.06 % LV volume Standard Deviation 11	1.9 % LV volume Standard Deviation 10

SECONDARY outcome

Timeframe: up to 36 hrs post surgery

Number of participants with new or worsening of cardiac dysrhythmias

Outcome measures

Measure	Cardioplegia: Custodiol HTK Solution n=55 Participants Custodiol HTK (histidine-tryptophan-ketoglutarate) cardioplegia: One liter of HTK solution (Custodiol; Koehler Chemi, Alsbach-Haenlien, Germany) contains the following components: 15 mmol/L sodium chloride, 9 mmol/L potassium chloride, 4 mmol/L magnesium chloride, 18 mmol/L histidine hydrochloride, 180 mmol/L histidine, 2 mmol/L tryptophan, 30 mmol/L mannitol, 0.015 mmol/L calcium chloride, 1 mmol/L potassium hydrogen 2-ketoglutarate, osmolarity 310 mOsm/kg, pH 7.02-7.20. Custodiol-HTK was delivered to establish and maintain cardiac arrest. After cross-clamping of the aorta approximately 1-2 L of Custodiol-HTK was infused into the ascending aorta over 6-8 minutes. Additional doses of 100-200 ml were administered as needed. Custodiol-HTK was delivered at a temperature of 4°C - 10°C.	Cold Blood Cardioplegia n=55 Participants Cold Blood Cardioplegia: One liter of cold blood cardioplegic solution, mixed at a ratio of 4:1 per Beaumont standard of care (blood /cardioplegic solution), contains the following in a 500 cc bag of D5W (dextrose 5% in water): 50meq/L potassium chloride, 37.5 meq/L sodium bicarbonate and 7.5 meq/L magnesium sulfate. After cross-clamping the aorta, at least 1000 mL of a 4:1 mixture of cold blood: cold crystalloid was administered at a pressure of 300 mmHg or less via a twin roller pump. Every 20 minutes an additional \> 200 mL was administered as needed. The cardioplegic solution was delivered at a temperature of 4°C - 8°C.
Cardiac Dysrhythmias	24 participants	30 participants

SECONDARY outcome

Timeframe: 30 days post procedure

Number of participants with all-cause mortality AS reported in the Society of Thoracic Surgeons (STS) database after 30 days postoperative

Outcome measures

Measure	Cardioplegia: Custodiol HTK Solution n=55 Participants Custodiol HTK (histidine-tryptophan-ketoglutarate) cardioplegia: One liter of HTK solution (Custodiol; Koehler Chemi, Alsbach-Haenlien, Germany) contains the following components: 15 mmol/L sodium chloride, 9 mmol/L potassium chloride, 4 mmol/L magnesium chloride, 18 mmol/L histidine hydrochloride, 180 mmol/L histidine, 2 mmol/L tryptophan, 30 mmol/L mannitol, 0.015 mmol/L calcium chloride, 1 mmol/L potassium hydrogen 2-ketoglutarate, osmolarity 310 mOsm/kg, pH 7.02-7.20. Custodiol-HTK was delivered to establish and maintain cardiac arrest. After cross-clamping of the aorta approximately 1-2 L of Custodiol-HTK was infused into the ascending aorta over 6-8 minutes. Additional doses of 100-200 ml were administered as needed. Custodiol-HTK was delivered at a temperature of 4°C - 10°C.	Cold Blood Cardioplegia n=55 Participants Cold Blood Cardioplegia: One liter of cold blood cardioplegic solution, mixed at a ratio of 4:1 per Beaumont standard of care (blood /cardioplegic solution), contains the following in a 500 cc bag of D5W (dextrose 5% in water): 50meq/L potassium chloride, 37.5 meq/L sodium bicarbonate and 7.5 meq/L magnesium sulfate. After cross-clamping the aorta, at least 1000 mL of a 4:1 mixture of cold blood: cold crystalloid was administered at a pressure of 300 mmHg or less via a twin roller pump. Every 20 minutes an additional \> 200 mL was administered as needed. The cardioplegic solution was delivered at a temperature of 4°C - 8°C.
All Cause Mortality	0 participants	0 participants

SECONDARY outcome

Timeframe: 30 days post procedure

Number of participants with cardiovascular-related mortality AS reported in the Society of Thoracic Surgeons (STS) database after 30 days postoperative

Outcome measures

Measure	Cardioplegia: Custodiol HTK Solution n=55 Participants Custodiol HTK (histidine-tryptophan-ketoglutarate) cardioplegia: One liter of HTK solution (Custodiol; Koehler Chemi, Alsbach-Haenlien, Germany) contains the following components: 15 mmol/L sodium chloride, 9 mmol/L potassium chloride, 4 mmol/L magnesium chloride, 18 mmol/L histidine hydrochloride, 180 mmol/L histidine, 2 mmol/L tryptophan, 30 mmol/L mannitol, 0.015 mmol/L calcium chloride, 1 mmol/L potassium hydrogen 2-ketoglutarate, osmolarity 310 mOsm/kg, pH 7.02-7.20. Custodiol-HTK was delivered to establish and maintain cardiac arrest. After cross-clamping of the aorta approximately 1-2 L of Custodiol-HTK was infused into the ascending aorta over 6-8 minutes. Additional doses of 100-200 ml were administered as needed. Custodiol-HTK was delivered at a temperature of 4°C - 10°C.	Cold Blood Cardioplegia n=55 Participants Cold Blood Cardioplegia: One liter of cold blood cardioplegic solution, mixed at a ratio of 4:1 per Beaumont standard of care (blood /cardioplegic solution), contains the following in a 500 cc bag of D5W (dextrose 5% in water): 50meq/L potassium chloride, 37.5 meq/L sodium bicarbonate and 7.5 meq/L magnesium sulfate. After cross-clamping the aorta, at least 1000 mL of a 4:1 mixture of cold blood: cold crystalloid was administered at a pressure of 300 mmHg or less via a twin roller pump. Every 20 minutes an additional \> 200 mL was administered as needed. The cardioplegic solution was delivered at a temperature of 4°C - 8°C.
Cardiovascular Mortality	0 participants	0 participants

SECONDARY outcome

Timeframe: up to 36 hours post procedure

time in hours from intubation to extubation, with intervening transport to the cardiac critical care unit.

Outcome measures

Measure	Cardioplegia: Custodiol HTK Solution n=55 Participants Custodiol HTK (histidine-tryptophan-ketoglutarate) cardioplegia: One liter of HTK solution (Custodiol; Koehler Chemi, Alsbach-Haenlien, Germany) contains the following components: 15 mmol/L sodium chloride, 9 mmol/L potassium chloride, 4 mmol/L magnesium chloride, 18 mmol/L histidine hydrochloride, 180 mmol/L histidine, 2 mmol/L tryptophan, 30 mmol/L mannitol, 0.015 mmol/L calcium chloride, 1 mmol/L potassium hydrogen 2-ketoglutarate, osmolarity 310 mOsm/kg, pH 7.02-7.20. Custodiol-HTK was delivered to establish and maintain cardiac arrest. After cross-clamping of the aorta approximately 1-2 L of Custodiol-HTK was infused into the ascending aorta over 6-8 minutes. Additional doses of 100-200 ml were administered as needed. Custodiol-HTK was delivered at a temperature of 4°C - 10°C.	Cold Blood Cardioplegia n=55 Participants Cold Blood Cardioplegia: One liter of cold blood cardioplegic solution, mixed at a ratio of 4:1 per Beaumont standard of care (blood /cardioplegic solution), contains the following in a 500 cc bag of D5W (dextrose 5% in water): 50meq/L potassium chloride, 37.5 meq/L sodium bicarbonate and 7.5 meq/L magnesium sulfate. After cross-clamping the aorta, at least 1000 mL of a 4:1 mixture of cold blood: cold crystalloid was administered at a pressure of 300 mmHg or less via a twin roller pump. Every 20 minutes an additional \> 200 mL was administered as needed. The cardioplegic solution was delivered at a temperature of 4°C - 8°C.
Time on Mechanically Assisted Ventilation	10.5 hours Interval 9.1 to 13.9	11.4 hours Interval 3.9 to 527.0

SECONDARY outcome

Timeframe: up to 36 hours post procedure

Population: Patients not receiving any vasopressors are excluded from this analysis

Total time in minutes on any vasopressor or inotropic agent, including norepinephrine, epinephrine, vasopressin, milrinone, dobutamine, dopamine and/or neo-synephrine

Outcome measures

Measure	Cardioplegia: Custodiol HTK Solution n=47 Participants Custodiol HTK (histidine-tryptophan-ketoglutarate) cardioplegia: One liter of HTK solution (Custodiol; Koehler Chemi, Alsbach-Haenlien, Germany) contains the following components: 15 mmol/L sodium chloride, 9 mmol/L potassium chloride, 4 mmol/L magnesium chloride, 18 mmol/L histidine hydrochloride, 180 mmol/L histidine, 2 mmol/L tryptophan, 30 mmol/L mannitol, 0.015 mmol/L calcium chloride, 1 mmol/L potassium hydrogen 2-ketoglutarate, osmolarity 310 mOsm/kg, pH 7.02-7.20. Custodiol-HTK was delivered to establish and maintain cardiac arrest. After cross-clamping of the aorta approximately 1-2 L of Custodiol-HTK was infused into the ascending aorta over 6-8 minutes. Additional doses of 100-200 ml were administered as needed. Custodiol-HTK was delivered at a temperature of 4°C - 10°C.	Cold Blood Cardioplegia n=43 Participants Cold Blood Cardioplegia: One liter of cold blood cardioplegic solution, mixed at a ratio of 4:1 per Beaumont standard of care (blood /cardioplegic solution), contains the following in a 500 cc bag of D5W (dextrose 5% in water): 50meq/L potassium chloride, 37.5 meq/L sodium bicarbonate and 7.5 meq/L magnesium sulfate. After cross-clamping the aorta, at least 1000 mL of a 4:1 mixture of cold blood: cold crystalloid was administered at a pressure of 300 mmHg or less via a twin roller pump. Every 20 minutes an additional \> 200 mL was administered as needed. The cardioplegic solution was delivered at a temperature of 4°C - 8°C.
Duration of Vasopressor / Inotropic Agent	340 minutes Interval 115.0 to 636.0	582 minutes Interval 154.0 to 1182.0

SECONDARY outcome

Timeframe: during operative procedure

Number of patients receiving vasopressor or inotropic infusion for greater than 20 minutes in the operating room, including norepinephrine, epinephrine, vasopressin, milrinone, dobutamine, dopamine and/or neo-synephrine.

Outcome measures

Measure	Cardioplegia: Custodiol HTK Solution n=55 Participants Custodiol HTK (histidine-tryptophan-ketoglutarate) cardioplegia: One liter of HTK solution (Custodiol; Koehler Chemi, Alsbach-Haenlien, Germany) contains the following components: 15 mmol/L sodium chloride, 9 mmol/L potassium chloride, 4 mmol/L magnesium chloride, 18 mmol/L histidine hydrochloride, 180 mmol/L histidine, 2 mmol/L tryptophan, 30 mmol/L mannitol, 0.015 mmol/L calcium chloride, 1 mmol/L potassium hydrogen 2-ketoglutarate, osmolarity 310 mOsm/kg, pH 7.02-7.20. Custodiol-HTK was delivered to establish and maintain cardiac arrest. After cross-clamping of the aorta approximately 1-2 L of Custodiol-HTK was infused into the ascending aorta over 6-8 minutes. Additional doses of 100-200 ml were administered as needed. Custodiol-HTK was delivered at a temperature of 4°C - 10°C.	Cold Blood Cardioplegia n=55 Participants Cold Blood Cardioplegia: One liter of cold blood cardioplegic solution, mixed at a ratio of 4:1 per Beaumont standard of care (blood /cardioplegic solution), contains the following in a 500 cc bag of D5W (dextrose 5% in water): 50meq/L potassium chloride, 37.5 meq/L sodium bicarbonate and 7.5 meq/L magnesium sulfate. After cross-clamping the aorta, at least 1000 mL of a 4:1 mixture of cold blood: cold crystalloid was administered at a pressure of 300 mmHg or less via a twin roller pump. Every 20 minutes an additional \> 200 mL was administered as needed. The cardioplegic solution was delivered at a temperature of 4°C - 8°C.
Postoperative Inotropic Infusion >20 Minutes	47 participants	43 participants

SECONDARY outcome

Timeframe: up to 100 days after admission

Duration of stay in ICU, from ICU admission to ICU discharge

Outcome measures

Measure	Cardioplegia: Custodiol HTK Solution n=55 Participants Custodiol HTK (histidine-tryptophan-ketoglutarate) cardioplegia: One liter of HTK solution (Custodiol; Koehler Chemi, Alsbach-Haenlien, Germany) contains the following components: 15 mmol/L sodium chloride, 9 mmol/L potassium chloride, 4 mmol/L magnesium chloride, 18 mmol/L histidine hydrochloride, 180 mmol/L histidine, 2 mmol/L tryptophan, 30 mmol/L mannitol, 0.015 mmol/L calcium chloride, 1 mmol/L potassium hydrogen 2-ketoglutarate, osmolarity 310 mOsm/kg, pH 7.02-7.20. Custodiol-HTK was delivered to establish and maintain cardiac arrest. After cross-clamping of the aorta approximately 1-2 L of Custodiol-HTK was infused into the ascending aorta over 6-8 minutes. Additional doses of 100-200 ml were administered as needed. Custodiol-HTK was delivered at a temperature of 4°C - 10°C.	Cold Blood Cardioplegia n=55 Participants Cold Blood Cardioplegia: One liter of cold blood cardioplegic solution, mixed at a ratio of 4:1 per Beaumont standard of care (blood /cardioplegic solution), contains the following in a 500 cc bag of D5W (dextrose 5% in water): 50meq/L potassium chloride, 37.5 meq/L sodium bicarbonate and 7.5 meq/L magnesium sulfate. After cross-clamping the aorta, at least 1000 mL of a 4:1 mixture of cold blood: cold crystalloid was administered at a pressure of 300 mmHg or less via a twin roller pump. Every 20 minutes an additional \> 200 mL was administered as needed. The cardioplegic solution was delivered at a temperature of 4°C - 8°C.
Intensive Care Unit (ICU) Length of Stay	3 days Interval 2.0 to 5.0	3 days Interval 2.0 to 5.0

SECONDARY outcome

Timeframe: up to 36 hours post procedure

Number or participants fulfilling at least two of the following 3 criteria: (1) CK-MB of 100 ug/L or more and/or troponin-I of 3.0 ug/L or more, (2) appearance of new postoperative Q waves on the EKG of more than 0.03 seconds, and (3) a new hypokinetic or akinetic area in the left or right ventricle by echocardiography.

Outcome measures

Measure	Cardioplegia: Custodiol HTK Solution n=55 Participants Custodiol HTK (histidine-tryptophan-ketoglutarate) cardioplegia: One liter of HTK solution (Custodiol; Koehler Chemi, Alsbach-Haenlien, Germany) contains the following components: 15 mmol/L sodium chloride, 9 mmol/L potassium chloride, 4 mmol/L magnesium chloride, 18 mmol/L histidine hydrochloride, 180 mmol/L histidine, 2 mmol/L tryptophan, 30 mmol/L mannitol, 0.015 mmol/L calcium chloride, 1 mmol/L potassium hydrogen 2-ketoglutarate, osmolarity 310 mOsm/kg, pH 7.02-7.20. Custodiol-HTK was delivered to establish and maintain cardiac arrest. After cross-clamping of the aorta approximately 1-2 L of Custodiol-HTK was infused into the ascending aorta over 6-8 minutes. Additional doses of 100-200 ml were administered as needed. Custodiol-HTK was delivered at a temperature of 4°C - 10°C.	Cold Blood Cardioplegia n=55 Participants Cold Blood Cardioplegia: One liter of cold blood cardioplegic solution, mixed at a ratio of 4:1 per Beaumont standard of care (blood /cardioplegic solution), contains the following in a 500 cc bag of D5W (dextrose 5% in water): 50meq/L potassium chloride, 37.5 meq/L sodium bicarbonate and 7.5 meq/L magnesium sulfate. After cross-clamping the aorta, at least 1000 mL of a 4:1 mixture of cold blood: cold crystalloid was administered at a pressure of 300 mmHg or less via a twin roller pump. Every 20 minutes an additional \> 200 mL was administered as needed. The cardioplegic solution was delivered at a temperature of 4°C - 8°C.
Myocardial Infarction	0 participants	0 participants

SECONDARY outcome

Timeframe: pre-operative

Population: Only patients for whom preoperative CK-MB levels were available were analyzed

CK-MB measured pre-operatively

Outcome measures

Measure	Cardioplegia: Custodiol HTK Solution n=38 Participants Custodiol HTK (histidine-tryptophan-ketoglutarate) cardioplegia: One liter of HTK solution (Custodiol; Koehler Chemi, Alsbach-Haenlien, Germany) contains the following components: 15 mmol/L sodium chloride, 9 mmol/L potassium chloride, 4 mmol/L magnesium chloride, 18 mmol/L histidine hydrochloride, 180 mmol/L histidine, 2 mmol/L tryptophan, 30 mmol/L mannitol, 0.015 mmol/L calcium chloride, 1 mmol/L potassium hydrogen 2-ketoglutarate, osmolarity 310 mOsm/kg, pH 7.02-7.20. Custodiol-HTK was delivered to establish and maintain cardiac arrest. After cross-clamping of the aorta approximately 1-2 L of Custodiol-HTK was infused into the ascending aorta over 6-8 minutes. Additional doses of 100-200 ml were administered as needed. Custodiol-HTK was delivered at a temperature of 4°C - 10°C.	Cold Blood Cardioplegia n=40 Participants Cold Blood Cardioplegia: One liter of cold blood cardioplegic solution, mixed at a ratio of 4:1 per Beaumont standard of care (blood /cardioplegic solution), contains the following in a 500 cc bag of D5W (dextrose 5% in water): 50meq/L potassium chloride, 37.5 meq/L sodium bicarbonate and 7.5 meq/L magnesium sulfate. After cross-clamping the aorta, at least 1000 mL of a 4:1 mixture of cold blood: cold crystalloid was administered at a pressure of 300 mmHg or less via a twin roller pump. Every 20 minutes an additional \> 200 mL was administered as needed. The cardioplegic solution was delivered at a temperature of 4°C - 8°C.
Biochemical Marker - Creatine Kinase MB Isoenzyme (CK-MB)	1.9 ng/mL Standard Deviation 1.2	2.6 ng/mL Standard Deviation 2.0

SECONDARY outcome

Timeframe: 24 hours post procedure

Population: Only patients for whom 24 hour CK-MB values were available were analyzed

CK-MB measured 24 hours post-operatively

Outcome measures

Measure	Cardioplegia: Custodiol HTK Solution n=53 Participants Custodiol HTK (histidine-tryptophan-ketoglutarate) cardioplegia: One liter of HTK solution (Custodiol; Koehler Chemi, Alsbach-Haenlien, Germany) contains the following components: 15 mmol/L sodium chloride, 9 mmol/L potassium chloride, 4 mmol/L magnesium chloride, 18 mmol/L histidine hydrochloride, 180 mmol/L histidine, 2 mmol/L tryptophan, 30 mmol/L mannitol, 0.015 mmol/L calcium chloride, 1 mmol/L potassium hydrogen 2-ketoglutarate, osmolarity 310 mOsm/kg, pH 7.02-7.20. Custodiol-HTK was delivered to establish and maintain cardiac arrest. After cross-clamping of the aorta approximately 1-2 L of Custodiol-HTK was infused into the ascending aorta over 6-8 minutes. Additional doses of 100-200 ml were administered as needed. Custodiol-HTK was delivered at a temperature of 4°C - 10°C.	Cold Blood Cardioplegia n=54 Participants Cold Blood Cardioplegia: One liter of cold blood cardioplegic solution, mixed at a ratio of 4:1 per Beaumont standard of care (blood /cardioplegic solution), contains the following in a 500 cc bag of D5W (dextrose 5% in water): 50meq/L potassium chloride, 37.5 meq/L sodium bicarbonate and 7.5 meq/L magnesium sulfate. After cross-clamping the aorta, at least 1000 mL of a 4:1 mixture of cold blood: cold crystalloid was administered at a pressure of 300 mmHg or less via a twin roller pump. Every 20 minutes an additional \> 200 mL was administered as needed. The cardioplegic solution was delivered at a temperature of 4°C - 8°C.
Biochemical Marker - Creatine Kinase MB Isoenzyme (CK-MB)	20 ng/mL Standard Deviation 14	24 ng/mL Standard Deviation 25

SECONDARY outcome

Timeframe: 48 hours post procedure

Population: Only patients for whom 48 hour CK-MB values are available are included in analysis

CK-MB measured 48 hours post-operatively

Outcome measures

Measure	Cardioplegia: Custodiol HTK Solution n=49 Participants Custodiol HTK (histidine-tryptophan-ketoglutarate) cardioplegia: One liter of HTK solution (Custodiol; Koehler Chemi, Alsbach-Haenlien, Germany) contains the following components: 15 mmol/L sodium chloride, 9 mmol/L potassium chloride, 4 mmol/L magnesium chloride, 18 mmol/L histidine hydrochloride, 180 mmol/L histidine, 2 mmol/L tryptophan, 30 mmol/L mannitol, 0.015 mmol/L calcium chloride, 1 mmol/L potassium hydrogen 2-ketoglutarate, osmolarity 310 mOsm/kg, pH 7.02-7.20. Custodiol-HTK was delivered to establish and maintain cardiac arrest. After cross-clamping of the aorta approximately 1-2 L of Custodiol-HTK was infused into the ascending aorta over 6-8 minutes. Additional doses of 100-200 ml were administered as needed. Custodiol-HTK was delivered at a temperature of 4°C - 10°C.	Cold Blood Cardioplegia n=52 Participants Cold Blood Cardioplegia: One liter of cold blood cardioplegic solution, mixed at a ratio of 4:1 per Beaumont standard of care (blood /cardioplegic solution), contains the following in a 500 cc bag of D5W (dextrose 5% in water): 50meq/L potassium chloride, 37.5 meq/L sodium bicarbonate and 7.5 meq/L magnesium sulfate. After cross-clamping the aorta, at least 1000 mL of a 4:1 mixture of cold blood: cold crystalloid was administered at a pressure of 300 mmHg or less via a twin roller pump. Every 20 minutes an additional \> 200 mL was administered as needed. The cardioplegic solution was delivered at a temperature of 4°C - 8°C.
Biochemical Marker - Creatine Kinase MB Isoenzyme (CK-MB)	6.0 ng/mL Standard Deviation 5.1	7.8 ng/mL Standard Deviation 7.0

SECONDARY outcome

Timeframe: pre-operatively

Population: Only patients for whom preoperative Troponin-I values were available were included in analysis

Troponin-I measured pre-operatively

Outcome measures

Measure	Cardioplegia: Custodiol HTK Solution n=52 Participants Custodiol HTK (histidine-tryptophan-ketoglutarate) cardioplegia: One liter of HTK solution (Custodiol; Koehler Chemi, Alsbach-Haenlien, Germany) contains the following components: 15 mmol/L sodium chloride, 9 mmol/L potassium chloride, 4 mmol/L magnesium chloride, 18 mmol/L histidine hydrochloride, 180 mmol/L histidine, 2 mmol/L tryptophan, 30 mmol/L mannitol, 0.015 mmol/L calcium chloride, 1 mmol/L potassium hydrogen 2-ketoglutarate, osmolarity 310 mOsm/kg, pH 7.02-7.20. Custodiol-HTK was delivered to establish and maintain cardiac arrest. After cross-clamping of the aorta approximately 1-2 L of Custodiol-HTK was infused into the ascending aorta over 6-8 minutes. Additional doses of 100-200 ml were administered as needed. Custodiol-HTK was delivered at a temperature of 4°C - 10°C.	Cold Blood Cardioplegia n=54 Participants Cold Blood Cardioplegia: One liter of cold blood cardioplegic solution, mixed at a ratio of 4:1 per Beaumont standard of care (blood /cardioplegic solution), contains the following in a 500 cc bag of D5W (dextrose 5% in water): 50meq/L potassium chloride, 37.5 meq/L sodium bicarbonate and 7.5 meq/L magnesium sulfate. After cross-clamping the aorta, at least 1000 mL of a 4:1 mixture of cold blood: cold crystalloid was administered at a pressure of 300 mmHg or less via a twin roller pump. Every 20 minutes an additional \> 200 mL was administered as needed. The cardioplegic solution was delivered at a temperature of 4°C - 8°C.
Cardiac Marker - Troponin-I	.03 ng/mL Standard Deviation .01	.03 ng/mL Standard Deviation .01

SECONDARY outcome

Timeframe: 24 hours post procedure

Population: Only patients for whom 24-hour Troponin-I values were available were included in analysis

Troponin-I measured 24 hours post-operative

Outcome measures

Measure	Cardioplegia: Custodiol HTK Solution n=54 Participants Custodiol HTK (histidine-tryptophan-ketoglutarate) cardioplegia: One liter of HTK solution (Custodiol; Koehler Chemi, Alsbach-Haenlien, Germany) contains the following components: 15 mmol/L sodium chloride, 9 mmol/L potassium chloride, 4 mmol/L magnesium chloride, 18 mmol/L histidine hydrochloride, 180 mmol/L histidine, 2 mmol/L tryptophan, 30 mmol/L mannitol, 0.015 mmol/L calcium chloride, 1 mmol/L potassium hydrogen 2-ketoglutarate, osmolarity 310 mOsm/kg, pH 7.02-7.20. Custodiol-HTK was delivered to establish and maintain cardiac arrest. After cross-clamping of the aorta approximately 1-2 L of Custodiol-HTK was infused into the ascending aorta over 6-8 minutes. Additional doses of 100-200 ml were administered as needed. Custodiol-HTK was delivered at a temperature of 4°C - 10°C.	Cold Blood Cardioplegia n=54 Participants Cold Blood Cardioplegia: One liter of cold blood cardioplegic solution, mixed at a ratio of 4:1 per Beaumont standard of care (blood /cardioplegic solution), contains the following in a 500 cc bag of D5W (dextrose 5% in water): 50meq/L potassium chloride, 37.5 meq/L sodium bicarbonate and 7.5 meq/L magnesium sulfate. After cross-clamping the aorta, at least 1000 mL of a 4:1 mixture of cold blood: cold crystalloid was administered at a pressure of 300 mmHg or less via a twin roller pump. Every 20 minutes an additional \> 200 mL was administered as needed. The cardioplegic solution was delivered at a temperature of 4°C - 8°C.
Cardiac Marker - Troponin-I	5.7 ng/mL Standard Deviation 5.4	7.8 ng/mL Standard Deviation 8.1

SECONDARY outcome

Timeframe: 48 hours post procedure

Population: Only patients for whom 48-hour Troponin-I values were available were included in analysis

Troponin-I measured 48 hours post-operative

Outcome measures

Measure	Cardioplegia: Custodiol HTK Solution n=49 Participants Custodiol HTK (histidine-tryptophan-ketoglutarate) cardioplegia: One liter of HTK solution (Custodiol; Koehler Chemi, Alsbach-Haenlien, Germany) contains the following components: 15 mmol/L sodium chloride, 9 mmol/L potassium chloride, 4 mmol/L magnesium chloride, 18 mmol/L histidine hydrochloride, 180 mmol/L histidine, 2 mmol/L tryptophan, 30 mmol/L mannitol, 0.015 mmol/L calcium chloride, 1 mmol/L potassium hydrogen 2-ketoglutarate, osmolarity 310 mOsm/kg, pH 7.02-7.20. Custodiol-HTK was delivered to establish and maintain cardiac arrest. After cross-clamping of the aorta approximately 1-2 L of Custodiol-HTK was infused into the ascending aorta over 6-8 minutes. Additional doses of 100-200 ml were administered as needed. Custodiol-HTK was delivered at a temperature of 4°C - 10°C.	Cold Blood Cardioplegia n=52 Participants Cold Blood Cardioplegia: One liter of cold blood cardioplegic solution, mixed at a ratio of 4:1 per Beaumont standard of care (blood /cardioplegic solution), contains the following in a 500 cc bag of D5W (dextrose 5% in water): 50meq/L potassium chloride, 37.5 meq/L sodium bicarbonate and 7.5 meq/L magnesium sulfate. After cross-clamping the aorta, at least 1000 mL of a 4:1 mixture of cold blood: cold crystalloid was administered at a pressure of 300 mmHg or less via a twin roller pump. Every 20 minutes an additional \> 200 mL was administered as needed. The cardioplegic solution was delivered at a temperature of 4°C - 8°C.
Cardiac Marker - Troponin-I	3.0 ng/mL Standard Deviation 3.3	4.8 ng/mL Standard Deviation 6.5

Adverse Events

Cardioplegia: Custodiol HTK Solution

Serious events: 3 serious events

Other events: 25 other events

Deaths: 0 deaths

Cold Blood Cardioplegia

Serious events: 9 serious events

Other events: 34 other events

Deaths: 0 deaths

Serious adverse events

Measure	Cardioplegia: Custodiol HTK Solution n=55 participants at risk Custodiol HTK (histidine-tryptophan-ketoglutarate) cardioplegia: One liter of HTK solution (Custodiol; Koehler Chemi, Alsbach-Haenlien, Germany) contains the following components: 15 mmol/L sodium chloride, 9 mmol/L potassium chloride, 4 mmol/L magnesium chloride, 18 mmol/L histidine hydrochloride, 180 mmol/L histidine, 2 mmol/L tryptophan, 30 mmol/L mannitol, 0.015 mmol/L calcium chloride, 1 mmol/L potassium hydrogen 2-ketoglutarate, osmolarity 310 mOsm/kg, pH 7.02-7.20. Custodiol-HTK was delivered to establish and maintain cardiac arrest. After cross-clamping of the aorta approximately 1-2 L of Custodiol-HTK was infused into the ascending aorta over 6-8 minutes. Additional doses of 100-200 ml were administered as needed. Custodiol-HTK was delivered at a temperature of 4°C - 10°C.	Cold Blood Cardioplegia n=55 participants at risk Cold Blood Cardioplegia: One liter of cold blood cardioplegic solution, mixed at a ratio of 4:1 per Beaumont standard of care (blood /cardioplegic solution), contains the following in a 500 cc bag of D5W (dextrose 5% in water): 50meq/L potassium chloride, 37.5 meq/L sodium bicarbonate and 7.5 meq/L magnesium sulfate. After cross-clamping the aorta, at least 1000 mL of a 4:1 mixture of cold blood: cold crystalloid was administered at a pressure of 300 mmHg or less via a twin roller pump. Every 20 minutes an additional \> 200 mL was administered as needed. The cardioplegic solution was delivered at a temperature of 4°C - 8°C.
Blood and lymphatic system disorders Profuse bleeding	1.8% 1/55 • Number of events 1 • AEs were evaluated from time of consent to 4 days after surgery. An assessment of medical records and case report forms were examined for AEs or SAEs. Reports were reviewed by the PI for accuracy and relation to study intervention.	0.00% 0/55 • AEs were evaluated from time of consent to 4 days after surgery. An assessment of medical records and case report forms were examined for AEs or SAEs. Reports were reviewed by the PI for accuracy and relation to study intervention.
Respiratory, thoracic and mediastinal disorders Acute Respiratory failure	0.00% 0/55 • AEs were evaluated from time of consent to 4 days after surgery. An assessment of medical records and case report forms were examined for AEs or SAEs. Reports were reviewed by the PI for accuracy and relation to study intervention.	1.8% 1/55 • Number of events 1 • AEs were evaluated from time of consent to 4 days after surgery. An assessment of medical records and case report forms were examined for AEs or SAEs. Reports were reviewed by the PI for accuracy and relation to study intervention.
Cardiac disorders Acute chest pain, shortness of breath	0.00% 0/55 • AEs were evaluated from time of consent to 4 days after surgery. An assessment of medical records and case report forms were examined for AEs or SAEs. Reports were reviewed by the PI for accuracy and relation to study intervention.	1.8% 1/55 • Number of events 1 • AEs were evaluated from time of consent to 4 days after surgery. An assessment of medical records and case report forms were examined for AEs or SAEs. Reports were reviewed by the PI for accuracy and relation to study intervention.
Cardiac disorders Atrial Fib with rapid ventricular response	0.00% 0/55 • AEs were evaluated from time of consent to 4 days after surgery. An assessment of medical records and case report forms were examined for AEs or SAEs. Reports were reviewed by the PI for accuracy and relation to study intervention.	1.8% 1/55 • Number of events 1 • AEs were evaluated from time of consent to 4 days after surgery. An assessment of medical records and case report forms were examined for AEs or SAEs. Reports were reviewed by the PI for accuracy and relation to study intervention.
Immune system disorders SOB, peripheral edema, mouth pain 16 days post-op	0.00% 0/55 • AEs were evaluated from time of consent to 4 days after surgery. An assessment of medical records and case report forms were examined for AEs or SAEs. Reports were reviewed by the PI for accuracy and relation to study intervention.	1.8% 1/55 • Number of events 1 • AEs were evaluated from time of consent to 4 days after surgery. An assessment of medical records and case report forms were examined for AEs or SAEs. Reports were reviewed by the PI for accuracy and relation to study intervention.
Surgical and medical procedures Mediastinal bleed	0.00% 0/55 • AEs were evaluated from time of consent to 4 days after surgery. An assessment of medical records and case report forms were examined for AEs or SAEs. Reports were reviewed by the PI for accuracy and relation to study intervention.	1.8% 1/55 • Number of events 1 • AEs were evaluated from time of consent to 4 days after surgery. An assessment of medical records and case report forms were examined for AEs or SAEs. Reports were reviewed by the PI for accuracy and relation to study intervention.
Infections and infestations Hospitalization	0.00% 0/55 • AEs were evaluated from time of consent to 4 days after surgery. An assessment of medical records and case report forms were examined for AEs or SAEs. Reports were reviewed by the PI for accuracy and relation to study intervention.	1.8% 1/55 • Number of events 1 • AEs were evaluated from time of consent to 4 days after surgery. An assessment of medical records and case report forms were examined for AEs or SAEs. Reports were reviewed by the PI for accuracy and relation to study intervention.
Vascular disorders CVA	1.8% 1/55 • Number of events 1 • AEs were evaluated from time of consent to 4 days after surgery. An assessment of medical records and case report forms were examined for AEs or SAEs. Reports were reviewed by the PI for accuracy and relation to study intervention.	0.00% 0/55 • AEs were evaluated from time of consent to 4 days after surgery. An assessment of medical records and case report forms were examined for AEs or SAEs. Reports were reviewed by the PI for accuracy and relation to study intervention.
Respiratory, thoracic and mediastinal disorders Community acquired pneumonia	1.8% 1/55 • Number of events 1 • AEs were evaluated from time of consent to 4 days after surgery. An assessment of medical records and case report forms were examined for AEs or SAEs. Reports were reviewed by the PI for accuracy and relation to study intervention.	0.00% 0/55 • AEs were evaluated from time of consent to 4 days after surgery. An assessment of medical records and case report forms were examined for AEs or SAEs. Reports were reviewed by the PI for accuracy and relation to study intervention.
Vascular disorders Femoral occlusion	0.00% 0/55 • AEs were evaluated from time of consent to 4 days after surgery. An assessment of medical records and case report forms were examined for AEs or SAEs. Reports were reviewed by the PI for accuracy and relation to study intervention.	1.8% 1/55 • Number of events 1 • AEs were evaluated from time of consent to 4 days after surgery. An assessment of medical records and case report forms were examined for AEs or SAEs. Reports were reviewed by the PI for accuracy and relation to study intervention.
Respiratory, thoracic and mediastinal disorders Respiratory failure	0.00% 0/55 • AEs were evaluated from time of consent to 4 days after surgery. An assessment of medical records and case report forms were examined for AEs or SAEs. Reports were reviewed by the PI for accuracy and relation to study intervention.	1.8% 1/55 • Number of events 1 • AEs were evaluated from time of consent to 4 days after surgery. An assessment of medical records and case report forms were examined for AEs or SAEs. Reports were reviewed by the PI for accuracy and relation to study intervention.
Cardiac disorders Emergent Coronary Bypass	0.00% 0/55 • AEs were evaluated from time of consent to 4 days after surgery. An assessment of medical records and case report forms were examined for AEs or SAEs. Reports were reviewed by the PI for accuracy and relation to study intervention.	1.8% 1/55 • Number of events 1 • AEs were evaluated from time of consent to 4 days after surgery. An assessment of medical records and case report forms were examined for AEs or SAEs. Reports were reviewed by the PI for accuracy and relation to study intervention.

Other adverse events

Measure	Cardioplegia: Custodiol HTK Solution n=55 participants at risk Custodiol HTK (histidine-tryptophan-ketoglutarate) cardioplegia: One liter of HTK solution (Custodiol; Koehler Chemi, Alsbach-Haenlien, Germany) contains the following components: 15 mmol/L sodium chloride, 9 mmol/L potassium chloride, 4 mmol/L magnesium chloride, 18 mmol/L histidine hydrochloride, 180 mmol/L histidine, 2 mmol/L tryptophan, 30 mmol/L mannitol, 0.015 mmol/L calcium chloride, 1 mmol/L potassium hydrogen 2-ketoglutarate, osmolarity 310 mOsm/kg, pH 7.02-7.20. Custodiol-HTK was delivered to establish and maintain cardiac arrest. After cross-clamping of the aorta approximately 1-2 L of Custodiol-HTK was infused into the ascending aorta over 6-8 minutes. Additional doses of 100-200 ml were administered as needed. Custodiol-HTK was delivered at a temperature of 4°C - 10°C.	Cold Blood Cardioplegia n=55 participants at risk Cold Blood Cardioplegia: One liter of cold blood cardioplegic solution, mixed at a ratio of 4:1 per Beaumont standard of care (blood /cardioplegic solution), contains the following in a 500 cc bag of D5W (dextrose 5% in water): 50meq/L potassium chloride, 37.5 meq/L sodium bicarbonate and 7.5 meq/L magnesium sulfate. After cross-clamping the aorta, at least 1000 mL of a 4:1 mixture of cold blood: cold crystalloid was administered at a pressure of 300 mmHg or less via a twin roller pump. Every 20 minutes an additional \> 200 mL was administered as needed. The cardioplegic solution was delivered at a temperature of 4°C - 8°C.
Cardiac disorders A-Fib or fA-Flutter	25.5% 14/55 • Number of events 14 • AEs were evaluated from time of consent to 4 days after surgery. An assessment of medical records and case report forms were examined for AEs or SAEs. Reports were reviewed by the PI for accuracy and relation to study intervention.	38.2% 21/55 • Number of events 21 • AEs were evaluated from time of consent to 4 days after surgery. An assessment of medical records and case report forms were examined for AEs or SAEs. Reports were reviewed by the PI for accuracy and relation to study intervention.
Blood and lymphatic system disorders Trombocytopenia	9.1% 5/55 • Number of events 5 • AEs were evaluated from time of consent to 4 days after surgery. An assessment of medical records and case report forms were examined for AEs or SAEs. Reports were reviewed by the PI for accuracy and relation to study intervention.	9.1% 5/55 • Number of events 5 • AEs were evaluated from time of consent to 4 days after surgery. An assessment of medical records and case report forms were examined for AEs or SAEs. Reports were reviewed by the PI for accuracy and relation to study intervention.
Cardiac disorders Heart Block (complete, 1st AV, 2 AV, 3 AV)	10.9% 6/55 • Number of events 6 • AEs were evaluated from time of consent to 4 days after surgery. An assessment of medical records and case report forms were examined for AEs or SAEs. Reports were reviewed by the PI for accuracy and relation to study intervention.	14.5% 8/55 • Number of events 8 • AEs were evaluated from time of consent to 4 days after surgery. An assessment of medical records and case report forms were examined for AEs or SAEs. Reports were reviewed by the PI for accuracy and relation to study intervention.
Respiratory, thoracic and mediastinal disorders Respiratory Failure	3.6% 2/55 • Number of events 2 • AEs were evaluated from time of consent to 4 days after surgery. An assessment of medical records and case report forms were examined for AEs or SAEs. Reports were reviewed by the PI for accuracy and relation to study intervention.	9.1% 5/55 • Number of events 5 • AEs were evaluated from time of consent to 4 days after surgery. An assessment of medical records and case report forms were examined for AEs or SAEs. Reports were reviewed by the PI for accuracy and relation to study intervention.
Surgical and medical procedures Bleeding (any)	9.1% 5/55 • Number of events 5 • AEs were evaluated from time of consent to 4 days after surgery. An assessment of medical records and case report forms were examined for AEs or SAEs. Reports were reviewed by the PI for accuracy and relation to study intervention.	5.5% 3/55 • Number of events 3 • AEs were evaluated from time of consent to 4 days after surgery. An assessment of medical records and case report forms were examined for AEs or SAEs. Reports were reviewed by the PI for accuracy and relation to study intervention.
Blood and lymphatic system disorders Acute blood loss anemina/any anemia	5.5% 3/55 • Number of events 3 • AEs were evaluated from time of consent to 4 days after surgery. An assessment of medical records and case report forms were examined for AEs or SAEs. Reports were reviewed by the PI for accuracy and relation to study intervention.	7.3% 4/55 • Number of events 4 • AEs were evaluated from time of consent to 4 days after surgery. An assessment of medical records and case report forms were examined for AEs or SAEs. Reports were reviewed by the PI for accuracy and relation to study intervention.
Cardiac disorders Junctional Rhythm	9.1% 5/55 • Number of events 5 • AEs were evaluated from time of consent to 4 days after surgery. An assessment of medical records and case report forms were examined for AEs or SAEs. Reports were reviewed by the PI for accuracy and relation to study intervention.	3.6% 2/55 • Number of events 2 • AEs were evaluated from time of consent to 4 days after surgery. An assessment of medical records and case report forms were examined for AEs or SAEs. Reports were reviewed by the PI for accuracy and relation to study intervention.
Respiratory, thoracic and mediastinal disorders Pneumothorax	7.3% 4/55 • Number of events 4 • AEs were evaluated from time of consent to 4 days after surgery. An assessment of medical records and case report forms were examined for AEs or SAEs. Reports were reviewed by the PI for accuracy and relation to study intervention.	1.8% 1/55 • Number of events 1 • AEs were evaluated from time of consent to 4 days after surgery. An assessment of medical records and case report forms were examined for AEs or SAEs. Reports were reviewed by the PI for accuracy and relation to study intervention.
Respiratory, thoracic and mediastinal disorders Pleural Effusion	5.5% 3/55 • Number of events 3 • AEs were evaluated from time of consent to 4 days after surgery. An assessment of medical records and case report forms were examined for AEs or SAEs. Reports were reviewed by the PI for accuracy and relation to study intervention.	5.5% 3/55 • Number of events 3 • AEs were evaluated from time of consent to 4 days after surgery. An assessment of medical records and case report forms were examined for AEs or SAEs. Reports were reviewed by the PI for accuracy and relation to study intervention.
Renal and urinary disorders Acute Kidney Failure/Renal Failure	1.8% 1/55 • Number of events 1 • AEs were evaluated from time of consent to 4 days after surgery. An assessment of medical records and case report forms were examined for AEs or SAEs. Reports were reviewed by the PI for accuracy and relation to study intervention.	5.5% 3/55 • Number of events 3 • AEs were evaluated from time of consent to 4 days after surgery. An assessment of medical records and case report forms were examined for AEs or SAEs. Reports were reviewed by the PI for accuracy and relation to study intervention.

Additional Information

Marc P. Sakwa, M.D.

William Beaumont Hospital

Phone: 248/898-0123

Email: marc.sakwa@beaumont.org

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place