Phase III Study Comparing Two Methods of Cardioplegia in Aortic Valve Surgery Custodiol-N Versus Custodiol (Custodiol-AV)

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

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 aortic valve surgery. The study design is a prospective, double blind, multicenter, randomized, Phase III comparison study intended to demonstrate superiority in surgical outcome between Custodiol and Custodiol-N as determined by CK-MB peak value 4-24 hours after opening of the aortic cross-clamp (primary endpoint), catecholamine requirement (cumulative dose) and cardiac Troponin T, occurrence of comorbid events postoperatively (e.g., myocardial infarction).

Study Overview

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

• Study Type: Interventional
• Enrollment (Actual): 530
• Phase: Phase 3

Contacts and Locations

Study Locations

• Germany
  • Aachen, Germany, 52074
    • Klinik für Thorax-, Herz- und Gefäßchirurgie, Uniklinik der RWTH Aachen
  • Hamburg, Germany, 20246
    • Klinik für Gefäßchirurgie, Universitäres Herzzentrum am UKE Hamburg
  • Baden-Württemberg
    • Heidelberg, Baden-Württemberg, Germany, 69120
      • Klinik für Herzchirurgie, Universitätsklinikum Heidelberg
  • Hessen
    • Rotenburg an der Fulda, Hessen, Germany, 36199
      • Klinik für Herz- und Gefäßchirurgie GmbH, Herz-Kreislauf-Zentrum Rotenburg
  • Sachsen
    • Leipzig, Sachsen, Germany, 04289
      • Klinik für Herzchirurgie Universität Leipzig/ Herzzentrum Leipzig
  • Thüringen
    • Jena, Thüringen, Germany, 07747
      • Klinik für Herz- und Thoraxchirurgie Universitätsklinikum Jena

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 30 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients >/= 30 and </= 85 years of age
• Male or female with aortic valve disease
• Able to understand character and individual consequences of the clinical trial and to provide written informed consent to participate in the study
• Women of childbearing potential (ie, those who have not undergone a hysterectomy or who have not been post-menopausal for at least 12 consecutive months) must test negative for pregnancy prior to bypass surgery.

Exclusion Criteria:

• History of recent (< 6 weeks) Q-wave myocardial infarction
• Left ventricular ejection fraction < 25% (as assessed by any one of the following: contrast ventriculography, multigated acquisition scanning [MUGA], or 2-D ECHO)
• Patients on intra-aortic balloon devices or with history of previous coronary artery bypass surgery
• Pregnant or lactating patients
• Patients who have participated in any other investigational studies within 30 days previous to enrollment
• Patients in cardiogenic shock (defined as a systolic BP < 90 mmHg for over one hour despite inotropic and chronotropic support)
• Patients with severe chronic obstructive lung disease (FEV1 < 50%)
• Previous cardiac valvular disease (clinical relevant)
• GFR <60 ml/min
• Planned Ross-procedure, Mitral valve surgery, Aortic valve reconstruction, double valve surgery, other concomitant operations excluding coronary artery bypass surgery or closing a patent foramen ovale
• Evidence of severe organic (e.g. cirrhosis of the liver) or psychiatric disease by history or physical examination
• History of alcohol abuse, illicit drug use, significant mental illness, physical dependence to any opioid, or any history of drug abuse or addiction within 12 months of study enrollment.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Factorial Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Custodiol-N; comparison of two cardioplegic solutions, Custodiol-N versus Custodiol, in aortic valve surgery	Drug: Custodiol-N; comparison of two cardioplegic solutions, Custodiol-N versus Custodiol, in aortic valve surgery
Active Comparator: Custodiol; comparison of two cardioplegic solutions, Custodiol-N versus Custodiol, in aortic valve surgery	Drug: Custodiol; comparison of two cardioplegic solutions, Custodiol-N versus Custodiol, in aortic valve surgery

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
peak value for CK-MB	measured at 4, 8, 12, 16, 20 and 24 hours after the release of the aortic cross clamp

Secondary Outcome Measures

Outcome Measure	Time Frame
Catecholamine requirement on SICU	within 24 hours (cumulative dose)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety parameters	documentation and reporting of AE and SAE	from time of the study inclusion up to the follow-up visit on day 5

Collaborators and Investigators

• Sponsor: Dr. F. Köhler Chemie GmbH
• Investigators: Principal Investigator: Gabor Szabó, Prof., Department of Cardiac Surgery, University of Heidelberg, Im Neuenheimer Feld 110, 69120 Heidelberg

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2014
• Primary Completion (Actual): November 16, 2018
• Study Completion (Actual): December 1, 2018

Study Registration Dates

• First Submitted: February 14, 2014
• First Submitted That Met QC Criteria: March 25, 2014
• First Posted (Estimate): March 28, 2014

Study Record Updates

• Last Update Posted (Actual): January 18, 2020
• Last Update Submitted That Met QC Criteria: January 14, 2020
• Last Verified: February 1, 2018

More Information

Terms related to this study

• Keywords: coronary bypass surgery; aortic valve disease; cardioplegic solutions
• Additional Relevant MeSH Terms: Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Heart Valve Diseases; Coronary Disease; Coronary Artery Disease; Aortic Valve Disease
• Other Study ID Numbers: CL-N-CSM-AV-III/05/12