Safety and Feasibility of Hyperkalemic Cardioplegia With Diazoxide in Cardiac Surgery (CPG-DZX) Trial

Johns Hopkins University30 enrolled

Overview

This study aims to confirm the safety and efficacy of diazoxide as an additive to hyperkalemic cardioplegia in patients undergoing cardiac surgery with cardiopulmonary bypass. The investigators hypothesize that diazoxide combined with hyperkalemic cardioplegia provides superior myocardial protection and reduced myocardial stunning compared with standard cardioplegia alone. Thirty patients will receive treatment. Safety will be assessed by comparing mean arterial blood pressure measurements, glucose levels and incidence of adverse events between the two groups. Efficacy will be assessed by comparing right and left ventricular function in pre-operative vs post-operative transesophageal echocardiograms, need for mechanical circulatory support, ease of separation from bypass and Vasoactive Inotrope Score (VIS) between the two groups. The information gained could pave the way for the use of Katp (Potassium-atp) channel openers to prevent stunning, improve patient outcomes, and reduce health care costs related to myocardial stunning that requires inotropic and mechanical support following cardiac surgery.

This is a Phase I clinical trial. Thirty patients total will receive treatment (IV Diazoxide added to cardioplegia). Diazoxide will be added to the first dose of cardioplegia only. Subsequent doses of cardioplegia will not contain additives.

Study Type

INTERVENTIONAL

Allocation

Purpose

PREVENTION

Masking

NONE

Enrollment

Conditions

Myocardial Stunning

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Age 18 years or older * Scheduled for cardiac surgery with cardiopulmonary bypass and cardioplegic arrest * Patient scheduled for elective cardiac surgery * If female participant of childbearing potential, she must agree to and be able to use a highly effective method of birth control (eg, barrier contraceptives, hormonal contraceptives, intrauterine devices, or sexual abstinence) continuously for six days post- diazoxide dose Exclusion Criteria: * Patient with Diabetes Mellitus on sulfonylurea medications * Scheduled for left ventricular assist device (LVAD) or heart transplant * Left ventricular ejection fraction \< 30% * Pre-operative placement or planned use of mechanical circulatory support during surgery * Allergy to Thiazide and its derivatives * History of gout * Patient is pregnant or breastfeeding * Patients with seizure disorders controlled by diphenylhydantoin * Patients with a history of cold agglutinins

Outcomes

Primary Outcomes

Safety as assessed by mean change in blood pressure

Mean blood pressure measurements in mmHg.

Time frame: From first dose of cardioplegia through 24 hours post operatively

Safety as assessed by change in blood glucose levels

Blood glucose levels in mg/dl.

Time frame: From first dose of cardioplegia through 48 hours post operatively

Safety as assessed by incidence of adverse events

Safety will be assessed by total number of adverse events.

Time frame: From first dose of cardioplegia through 7 days post operatively or discharge, whichever comes first

Secondary Outcomes

Efficacy as assessed by change in ejection fraction

Comparison of right and left ventricular function (measured as a percentage) on pre and post operative Transesophageal echocardiograms

Time frame: Day of surgery (pre and post surgery)

Efficacy as assessed by use of mechanical circulatory support

Incidence of mechanical circulatory support use will be used in the assessment of efficacy.

Time frame: 48 hours post operatively

Efficacy as assessed by change in Vasoactive Inotropic Score (VIS)

Comparison of VIS Score with values from 0 to \>45, with lower scores indicating medication efficacy (0e5, \>5e15, \>15e30, \>30e45, and \>45 points).

Time frame: 0, 24, 48 and 72 hours post operatively

Efficacy as assessed by time to separate from Cardiopulmonary Bypass (CPB)

From time of first turn down of CPB to CPB end time measured in minutes.

Time frame: Day of surgery