Phase III Study Comparing Two Methods of Cardioplegia in Coronary Artery Bypass Surgery

A Prospective Randomized Double Blind Multicenter Phase III Study Comparing Two Methods of Cardioplegia in Coronary Artery Bypass Surgery Custodiol-N Versus Custodiol

Comparison of the cardioprotective effects and safety of two cardioplegic solutions (solutions used during a cardiac arrest in the heart surgery) in patients undergoing cardiopulmonary bypass for coronary artery bypass surgery.

Study Overview

• Status: Completed
• Conditions: Coronary Artery Disease (CAD)
• Intervention / Treatment: Drug: Custodiol; Drug: Custodiol-N

Detailed Description

The objective of this investigation is to compare the cardioprotective effects and safety of two cardioplegic solutions, HTK Cardioplegic Solution (Custodiol) and Custodiol-N in patients undergoing cardiopulmonary bypass for coronary artery bypass surgery. The study design is a prospective, double blind, multicenter, randomized, Phase III comparison study intended to demonstrate non-inferiority in surgical outcome between Custodiol and Custodiol-N as determined by CK-MB area under the curve (primary endpoint), catecholamine requirement(cumulative dose) and cardiac Troponin T, occurrence of comorbid events postoperatively (e.g., myocardial infarction).

• Study Type: Interventional
• Enrollment (Actual): 102
• Phase: Phase 2

Contacts and Locations

Study Locations

• Germany
  • Essen, Germany, 45147
    • Klinik für Thorax- und Kardiovaskuläre Chirurgie, Universitätsklinikum Essen
  • Heidelberg, Germany, 69120
    • Abt. Herzchirugie, Universitätsklinikum Heidelberg
  • Jena, Germany, 07740
    • Klinik für Herz- und Thoraxchirurgie, Universitätsklinikum Jena
  • Leipzig, Germany, 04289
    • Herzzentrum Leipzig GmbH

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 35 years to 80 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

The study population will be selected from patients of either sex with coronary artery disease (CAD) who are to undergo cardiopulmonary bypass for coronary artery bypass surgery.

1. Patients >/=35 and </=80 years of age
2. Male or female with 2 or 3 vessel coronary disease, who are scheduled for elective CBP surgery for coronary revascularisation

3. Presence of definite CAD for which surgical intervention is deemed necessary, without evidence of ongoing infarction.

   Patients with unstable angina can be included as long as there is no objective (negative cardiac isoenzymes in the immediate six hours preceding CABG, current intravenous use of nitrate therapy) or subjective (absence of prolonged symptoms suggestive of coronary insufficiency that do not respond to pharmacologic intervention) evidence of myocardial necrosis.

4. Eligibility for Swan-Ganz-Catheter
5. Able to understand character and individual consequences of the clinical trial and to provide written informed consent to participate in the study
6. No evidence of severe organic or psychiatric disease by history or physical examination
7. No history of alcohol abuse, illicit drug use, significant mental illness, physical dependence to any opioid, or no any history of drug abuse or addiction within 12 months of study enrollment.

Exclusion Criteria:

1. Patients undergoing valve repair or replacement
2. History of recent (< 6 weeks) Q-wave myocardial infarction
3. Left ventricular ejection fraction < 35% (as assessed by any one of the following: contrast ventriculography, multigated acquisition scanning [MUGA], or 2-D ECHO)
4. Patients on intra-aortic balloon devices or with history of previous coronary artery bypass surgery
5. Pregnant or lactating patients
6. Patients who have participated in any other investigational studies within 30 days previous to enrollment
7. Patients in cardiogenic shock (defined as a systolic BP < 90 mmHg for over one hour despite inotropic and chronotropic support)
8. Patients with severe chronic obstructive lung disease (FEV1 < 50%)
9. Previous cardiac valvular disease (clinical relevant)
10. Dialysis or creatinine > 2 mmol/L
11. BMS-Stent < 4 weeks
12. DES-Stent < 6 month
13. Guidance depended Plavix therapy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Custodiol; After cross clamping of the aorta on cardiopulmonary bypass, the Custodiol solution, at a temperature of 4 - 6°C, will be infused antegrade into the root of the aorta.	Drug: Custodiol; Route of administration: by infusion duration: infusion technique will be continued for seven minutes dosage: until 1500-2000 mL of solution have been infused
EXPERIMENTAL: Custodiol-N; After cross clamping of the aorta on cardiopulmonary bypass, the Custodiol-N solution, at a temperature of 4 - 6°C, will be infused antegrade into the root of the aorta.	Drug: Custodiol-N; Route of administration: by infusion Dosage: will be infused antegrade into the root of the aorta until 1500-2000 mL of solution have been infused Duration: infusion technique will be continued for seven minutes

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
CK-MB area under the curve within 24 hours	Measurements will be carried out at the following timepoints: 4,8,12,16,20,24 hours (± 30 min) after release of the aortic cross clamp	Up to 24 hours after the aortic clamp release

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Catecholamine requirement	Catecholamine requirement on surgical ICU within 24 hours	24 hours (cumulative dose)
CK-MB peak	CK-MB peak on the days 2, 3, 4 and 5 after removal of aortic cross clamp	Up to day 5
Mortality any time during post-op through Day 30	Mortality will be documented at any time during post-op through Day 30	Up to Day 30

Collaborators and Investigators

• Sponsor: Dr. F. Köhler Chemie GmbH
• Investigators: Principal Investigator: Gabor Szabo, Prof. Dr., Department of Cardiac Surgery of University of Heidelberg; Principal Investigator: Nikolaus Pizanis, Dr., Klinik für Thorax- und Kardiovaskuläre Chirurgie, Universitätsklinikum Essen; Principal Investigator: Florian Wagner, Dr., Klinik für Herz- und Gefäßchirurgie, Universitäts-Krankenhaus Eppendorf; Principal Investigator: Thorsten Doenst, Prof. Dr., Klinik für Herz- und Thoraxchirurgie, Universitätsklinikum Jena; Principal Investigator: Martin Misfeld, Dr., Herzzentrum Leipzig GmbH, Klinik für Herzchirurgie

Study record dates

Study Major Dates

• Study Start: March 1, 2011
• Primary Completion (ACTUAL): May 1, 2012
• Study Completion (ACTUAL): July 1, 2012

Study Registration Dates

• First Submitted: September 29, 2011
• First Submitted That Met QC Criteria: September 29, 2011
• First Posted (ESTIMATE): September 30, 2011

Study Record Updates

• Last Update Posted (ESTIMATE): May 17, 2013
• Last Update Submitted That Met QC Criteria: May 16, 2013
• Last Verified: May 1, 2013

More Information

Terms related to this study

• Keywords: CAD, ACVB
• Additional Relevant MeSH Terms: Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Coronary Disease; Coronary Artery Disease
• Other Study ID Numbers: CL-N-CSM-III/01/08