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

Phase 2

Completed

Conditions: Heart Diseases
Valvular Heart Disease
Myocardial Ischemia
Coronary Disease
Coronary Artery Disease

Interventions: Drug: Cold Blood Cardioplegia
Drug: Custodiol HTK

Registration Number: NCT01681095

Lead Sponsor: Marc Sakwa, MD

Brief Summary: The purpose of the study is to demonstrate that Custodiol-HTK is not inferior to cold cardioplegic solution in patients undergoing cardiovascular surgery requiring cardioplegic arrest.

Detailed Description: The objective of this study is to demonstrate that Custodiol is not inferior to cold cardioplegic solution for myocardial protection by comparing standard cold blood cardioplegia to Custodiol solution with respect to myocardial injury as measured by Creatine phosphokinase MB isoenzyme (CK-MB),troponin-I at 7 hours post surgery and changes in ejection fraction by trans-thoracic echocardiogram (TTE)or trans-esophageal echocardiogram (TEE) at 24 hours post surgery.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 110

Inclusion Criteria

Patients undergoing scheduled cardiac surgery requiring cardioplegic arrest with expected cross clamp time>45 minutes
Patients age 18 and older

Exclusion Criteria

Pregnant women*
Urgent or emergent cases
Repeat cardiovascular surgical procedures
Patients on dialysis
Any known allergies to components of either cardioplegia solution *All women of child bearing potential must have a negative serum or urine pregnancy test.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Cold Blood Cardioplegia	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.
Cardioplegia: Custodiol HTK Solution	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.

Primary Outcome Measures

Name	Time	Method
Changes in Left Ventricular (LV) Ejection Fraction (EF) by Transthoracic Echocardiogram (TTE)	Baseline and 24 hours post surgery	LV ejection fraction by TTE, difference from baseline at 24 hours post surgery
Change in Creatine Phosphokinase-MB Isoenzyme (CK-MB)	Baseline and 7 hours post surgery	Creatine phosphokinase MB isoenzyme (CK-MB) difference from baseline 7 hours post surgery
Change in Troponin I	Baseline and 7 hours post surgery	Troponin I values, difference from baseline 7 hours post surgery

Secondary Outcome Measures

Name	Time	Method
Cardiac Dysrhythmias	up to 36 hrs post surgery	Number of participants with new or worsening of cardiac dysrhythmias
Duration of Vasopressor / Inotropic Agent	up to 36 hours post procedure	Total time in minutes on any vasopressor or inotropic agent, including norepinephrine, epinephrine, vasopressin, milrinone, dobutamine, dopamine and/or neo-synephrine
Time on Mechanically Assisted Ventilation	up to 36 hours post procedure	time in hours from intubation to extubation, with intervening transport to the cardiac critical care unit.
Intensive Care Unit (ICU) Length of Stay	up to 100 days after admission	Duration of stay in ICU, from ICU admission to ICU discharge
Cardiac Marker - Troponin-I	48 hours post procedure	Troponin-I measured 48 hours post-operative
Cardiovascular Mortality	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
Myocardial Infarction	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.
Biochemical Marker - Creatine Kinase MB Isoenzyme (CK-MB)	48 hours post procedure	CK-MB measured 48 hours post-operatively
All Cause Mortality	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
Postoperative Inotropic Infusion >20 Minutes	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.