Custodiol-HTK (Histidine-tryptophan-ketoglutarate) Solution as a Cardioplegic Agent
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ClinicalTrials.gov Identifier: NCT01681095 |
Recruitment Status
:
Completed
First Posted
: September 7, 2012
Results First Posted
: March 1, 2017
Last Update Posted
: March 1, 2017
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Condition or disease | Intervention/treatment | Phase |
---|---|---|
Coronary Artery Disease Myocardial Ischemia Coronary Disease Heart Diseases Valvular Heart Disease | Drug: Custodiol HTK Drug: Cold Blood Cardioplegia | Phase 2 |
Study Type : | Interventional (Clinical Trial) |
Actual Enrollment : | 110 participants |
Allocation: | Randomized |
Intervention Model: | Parallel Assignment |
Masking: | None (Open Label) |
Primary Purpose: | Treatment |
Official Title: | Custodiol-HTK Solution as a Cardioplegic Agent- A Prospective Non-Inferiority Randomized Clinical Trial |
Study Start Date : | August 2012 |
Actual Primary Completion Date : | August 2014 |
Actual Study Completion Date : | April 2016 |

Arm | Intervention/treatment |
---|---|
Experimental: 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. |
Drug: Custodiol HTK
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. The cardioplegic solution was delivered at a temperature of 4°C - 10°C.
Other Name: Histidine-tryptophan-ketoglutarate cardioplegia solution
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Active Comparator: 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. |
Drug: Cold Blood Cardioplegia
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 in an antegrade/retrograde fashion throughout the remainder of the case. The cardioplegic solution was delivered at a temperature of 4°C - 8°C.
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- Change in Creatine Phosphokinase-MB Isoenzyme (CK-MB) [ Time Frame: Baseline and 7 hours post surgery ]Creatine phosphokinase MB isoenzyme (CK-MB) difference from baseline 7 hours post surgery
- Change in Troponin I [ Time Frame: Baseline and 7 hours post surgery ]Troponin I values, difference from baseline 7 hours post surgery
- Changes in Left Ventricular (LV) Ejection Fraction (EF) by Transthoracic Echocardiogram (TTE) [ Time Frame: Baseline and 24 hours post surgery ]LV ejection fraction by TTE, difference from baseline at 24 hours post surgery
- Cardiac Dysrhythmias [ Time Frame: up to 36 hrs post surgery ]Number of participants with new or worsening of cardiac dysrhythmias
- All Cause Mortality [ Time Frame: 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
- Cardiovascular Mortality [ Time Frame: 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
- Time on Mechanically Assisted Ventilation [ Time Frame: up to 36 hours post procedure ]time in hours from intubation to extubation, with intervening transport to the cardiac critical care unit.
- Duration of Vasopressor / Inotropic Agent [ Time Frame: 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
- Postoperative Inotropic Infusion >20 Minutes [ Time Frame: 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.
- Intensive Care Unit (ICU) Length of Stay [ Time Frame: up to 100 days after admission ]Duration of stay in ICU, from ICU admission to ICU discharge
- Myocardial Infarction [ Time Frame: 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) [ Time Frame: pre-operative ]CK-MB measured pre-operatively
- Biochemical Marker - Creatine Kinase MB Isoenzyme (CK-MB) [ Time Frame: 24 hours post procedure ]CK-MB measured 24 hours post-operatively
- Biochemical Marker - Creatine Kinase MB Isoenzyme (CK-MB) [ Time Frame: 48 hours post procedure ]CK-MB measured 48 hours post-operatively
- Cardiac Marker - Troponin-I [ Time Frame: pre-operatively ]Troponin-I measured pre-operatively
- Cardiac Marker - Troponin-I [ Time Frame: 24 hours post procedure ]Troponin-I measured 24 hours post-operative
- Cardiac Marker - Troponin-I [ Time Frame: 48 hours post procedure ]Troponin-I measured 48 hours post-operative

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Ages Eligible for Study: | 18 Years and older (Adult, Senior) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
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.

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01681095
United States, Michigan | |
William Beaumont Hospital | |
Royal Oak, Michigan, United States, 48073 |
Principal Investigator: | Marc Sakwa, M.D. | Beaumont Health System |
Publications:
Responsible Party: | Marc Sakwa, MD, Principal Investigator, William Beaumont Hospitals |
ClinicalTrials.gov Identifier: | NCT01681095 History of Changes |
Other Study ID Numbers: |
2012-125 |
First Posted: | September 7, 2012 Key Record Dates |
Results First Posted: | March 1, 2017 |
Last Update Posted: | March 1, 2017 |
Last Verified: | January 2017 |
Individual Participant Data (IPD) Sharing Statement: | |
Plan to Share IPD: | No |
Keywords provided by Marc Sakwa, MD, William Beaumont Hospitals:
Physiological Effects of Drugs Cardiovascular Agents Therapeutic Uses Pharmacologic Actions Mannitol Cardiac Surgery Cardioplegic Solutions |
HTK solution Myocardial protection Coronary Artery Disease Myocardial Ischemia Coronary Disease Heart Diseases |
Additional relevant MeSH terms:
Coronary Artery Disease Myocardial Ischemia Coronary Disease Heart Diseases Ischemia Heart Valve Diseases Cardiovascular Diseases Arteriosclerosis Arterial Occlusive Diseases Vascular Diseases Pathologic Processes Pharmaceutical Solutions Tryptophan Cardioplegic Solutions |
Mannitol Procaine Antidepressive Agents, Second-Generation Antidepressive Agents Psychotropic Drugs Diuretics, Osmotic Diuretics Natriuretic Agents Physiological Effects of Drugs Anesthetics, Local Anesthetics Central Nervous System Depressants Sensory System Agents Peripheral Nervous System Agents |