Safety and Efficacy of IV Diazoxide as an Additive to Hyperkalemic Cardioplegia in Patients Undergoing Cardiac Surgery With Cardiopulmonary Bypass

A Randomized Placebo Controlled Single Center Phase 1 Study to Evaluate Safety and Efficacy of IV Diazoxide as an Additive to Hyperkalemic Cardioplegia in Patients Undergoing Cardiac Surgery With Cardiopulmonary Bypass

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. The investigators will randomize 30 patients in a 2:1 fashion to treatment vs control. 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.

Study Overview

• Status: Withdrawn
• Conditions: Myocardial Stunning
• Intervention / Treatment: Drug: IV Diazoxide; Other: Placebo

Detailed Description

This is a randomized blinded Phase I clinical trial. Thirty patients total will be randomized on a 2:1 basis to treatment (IV Diazoxide added to cardioplegia) vs control (cardioplegia alone). Diazoxide will be added to the first dose of cardioplegia only. Subsequent doses of cardioplegia will not contain additives.

• Study Type: Interventional
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Johns Hopkins Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age 18 years or older
• Scheduled for cardiac surgery with cardiopulmonary bypass and cardioplegic arrest
• Patient scheduled for elective cardiac surgery

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Diazoxide; IV Diazoxide as additive to hypothermic hyperkalemic cardioplegia.	Drug: IV Diazoxide; 500 micromoles added to one liter of cardioplegia
Placebo Comparator: Placebo; Placebo as additive to hypothermic hyperkalemic cardioplegia.	Other: Placebo; Placebo added to one liter of cardioplegia

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety as assessed by mean change in blood pressure	Mean blood pressure measurements in mmHg.	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.	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.	From first dose of cardioplegia through 7 days post operatively or discharge, whichever comes first

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	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.	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).	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.	Day of surgery

Collaborators and Investigators

• Sponsor: Johns Hopkins University
• Investigators: Principal Investigator: Jennifer Lawton, MD, Johns Hopkins University

Study record dates

Study Major Dates

• Study Start (Anticipated): September 1, 2023
• Primary Completion (Anticipated): August 30, 2025
• Study Completion (Anticipated): October 30, 2025

Study Registration Dates

• First Submitted: March 31, 2021
• First Submitted That Met QC Criteria: April 2, 2021
• First Posted (Actual): April 5, 2021

Study Record Updates

• Last Update Posted (Actual): September 19, 2022
• Last Update Submitted That Met QC Criteria: September 15, 2022
• Last Verified: September 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Myocardial Stunning; Antihypertensive Agents; Vasodilator Agents; Diazoxide
• Other Study ID Numbers: IRB00265542

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No