Custodiol-HTK Solution as a Cardioplegic Agent

This study has been completed.
Sponsor:
Collaborator:
Essential Pharmaceuticals, LLC
Information provided by (Responsible Party):
Marc Sakwa, MD, William Beaumont Hospitals
ClinicalTrials.gov Identifier:
NCT01681095
First received: August 10, 2012
Last updated: June 24, 2014
Last verified: June 2014
  Purpose

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.


Condition Intervention 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
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Custodiol-HTK Solution as a Cardioplegic Agent- A Prospective Non-Inferiority Randomized Clinical Trial

Resource links provided by NLM:


Further study details as provided by William Beaumont Hospitals:

Primary Outcome Measures:
  • Creatine phosphokinase MB isoenzyme (CK-MB)and troponin-I [ Time Frame: 7 hours post surgery ] [ Designated as safety issue: Yes ]

    To demonstrate that Custodiol-HTK 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:

    o Creatine phosphokinase MB isoenzyme (CK-MB)and troponin-I at 7 hours post surgery


  • Changes in ejection fraction by TTE [ Time Frame: at 24 hours post surgery ] [ Designated as safety issue: Yes ]

    To demonstrate that Custodiol-HTK is not inferior to cold cardioplegic solution for myocardial protection by comparing standard cold blood cardioplegia to Custodiol solution with respect tomyocardial injury as measured by:

    o Changes in ejection fraction by TTE at 24 hours post surgery



Secondary Outcome Measures:
  • Cardiac dysrhythmias [ Time Frame: up to 36 hrs post surgery ] [ Designated as safety issue: Yes ]
    The frequency of new or worsening of cardiac dysrhythmias will be compared between the two randomization arms.

  • All cause mortality [ Time Frame: 30 days post procedure ] [ Designated as safety issue: No ]
    All cause mortality and cardiovascular related mortality will be recorded. A Society of Thoracic Surgeons (STS) database review will be conducted post-op after 30 days to assess for cause mortality

  • Time on Mechanically Assisted Ventilation [ Time Frame: up to 36 hours post procedure ] [ Designated as safety issue: No ]
    time of intubation, time of arrival in the cardiac critical care unit and time of extubation.

  • Biochemical Markers - Creatine phosphokinase MB isoenzyme (CK-MB)and troponin [ Time Frame: 24 and 48 hours ] [ Designated as safety issue: Yes ]
    Biochemical Markers - Creatine phosphokinase MB isoenzyme(CK-MB)and troponin-I cardiac markers will be measured preoperatively, at 24 and 48 hours postoperatively1

  • Duration of Vasopressor / Inotropic Agent [ Time Frame: up to 36 hours post procedure ] [ Designated as safety issue: Yes ]
    Postoperative inotropic support greater than 20 minutes will be recorded.

  • ICU Length of Stay [ Time Frame: ICU length of stay in total hours of an expected average of 3 days ] [ Designated as safety issue: No ]
    Participants will be followed for the duration of their hospital stay an expected average of 5 days. The ICU length of stay is expected to average 3 days.

  • Arterial Blood Gases [ Time Frame: up to 36 hours post procedure ] [ Designated as safety issue: Yes ]
    recorded in surgery after anesthesia induction, upon arrival to ICU, after accelerated vent wean and after spontaneous breathing trial.

  • Creatinine Levels [ Time Frame: 24 and 48 hours post procedure ] [ Designated as safety issue: Yes ]
  • Myocardial Infarction [ Time Frame: up to 36 hours post procedure ] [ Designated as safety issue: Yes ]
    Two of the following 3 criteria will need to be fulfilled to diagnose a myocardial infarction: (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.


Other Outcome Measures:
  • Q waves on EKG of more than 0.03 seconds [ Time Frame: 24 and 48 hours post procedure ] [ Designated as safety issue: Yes ]
    A 12-lead EKG will be recorded daily, upon arrival to the ICU, at 24 and 48 hours post-op. These will be compared with a pre-operative EKG for changes relating to Q waves or dysrhythmias.


Enrollment: 110
Study Start Date: August 2012
Study Completion Date: May 2014
Primary Completion Date: May 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Cardioplegia: Custodiol HTK Solution

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-HTKcardioplegia will be delivered to establish and maintain cardiac arrest. After cross-clamping of the aorta approximately 1-2L of Custodiol-HTK will be infused into the ascending aorta over 6-8 minutes. Additional doses of 100-200 ml may be administered as needed. The cardioplegic solution will be delivered at a temperature of 4°C - 10°C

Drug: Custodiol HTK
After cross-clamping of the aorta approximately 1-2L of Custodiol-HTK will be infused into the ascending aorta over 6-8 minutes. Additional doses of 100-200 ml may be administered as needed. The cardioplegic solution will be delivered at a temperature of 4°C - 10°C.
Active Comparator: Cold Blood Cardioplegia

Blood Cardioplegic Solution: One liter of cold blood cardioplegic solution, mixed at a ratio of 4:1 per Beaumont standard of care (blood /cardioplegic solution)22, contains the following components in a 500cc bag of D5W: 50meq/L potassium chloride, 37.5 meq/L sodium bicarbonate and 7.5 meq/L magnesium sulfate.

Cold blood cardioplegia will be administered after cross-clamping the aorta, at least 1000mL of a 4:1 mixture of cold blood: cold crystalloid will be administered at a pressure of 300mmHg or less via a twin roller pump. Every 20 minutes an additional > 200mL will be administered in an antegrade/retrograde fashion throughout the remainder of the case. The cardioplegic solution will be delivered at a temperature of 4°C - 8°C.

Drug: Cold Blood Cardioplegia
After cross-clamping the aorta, at least 1000mL of a 4:1 mixture of cold blood: cold crystalloid will be administered at a pressure of 300mmHg or less via a twin roller pump. Every 20 minutes an additional > 200mL will be administered in an antegrade/retrograde fashion throughout the remainder of the case. The cardioplegic solution will be delivered at a temperature of 4°C - 8°C.

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01681095

Locations
United States, Michigan
William Beaumont Hospital
Royal Oak, Michigan, United States, 48073
Sponsors and Collaborators
Marc Sakwa, MD
Essential Pharmaceuticals, LLC
Investigators
Principal Investigator: Marc Sakwa, M.D. Beaumont Health System
  More Information

Publications:

Responsible Party: Marc Sakwa, MD, Principal Investigator, William Beaumont Hospitals
ClinicalTrials.gov Identifier: NCT01681095     History of Changes
Other Study ID Numbers: HIC# 2012-125
Study First Received: August 10, 2012
Last Updated: June 24, 2014
Health Authority: United States: Institutional Review Board
United States: Food and Drug Administration

Keywords provided by William Beaumont Hospitals:
Heart Diseases
Physiological Effects of Drugs
Cardiovascular Agents
Therapeutic Uses
Pharmacologic Actions
Mannitol
Cardiac Surgery
Cardiovascular agents
Cardioplegic Solutions
HTK solution
Myocardial protection
Coronary Artery Disease
Myocardial Ischemia
Coronary Disease

Additional relevant MeSH terms:
Heart Diseases
Coronary Artery Disease
Myocardial Ischemia
Coronary Disease
Heart Valve Diseases
Ischemia
Cardiovascular Diseases
Arteriosclerosis
Arterial Occlusive Diseases
Vascular Diseases
Pathologic Processes
Cardioplegic Solutions
Cardiovascular Agents
Mannitol
Procaine
Physiological Effects of Drugs
Therapeutic Uses
Pharmacologic Actions
Diuretics, Osmotic
Diuretics
Natriuretic Agents
Anesthetics, Local
Anesthetics
Central Nervous System Depressants
Sensory System Agents
Peripheral Nervous System Agents
Central Nervous System Agents

ClinicalTrials.gov processed this record on July 22, 2014