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

Myocardial Stunning Clinical Trial

Official title:

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

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT04830982
• Other study ID #: IRB00265542
• Status: Withdrawn
• Phase: Phase 1
• Start date: September 1, 2023
• Est. completion date: October 30, 2025

Study information

• Verified date: September 2022
• Source: Johns Hopkins University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: October 30, 2025
• Est. primary completion date: August 30, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Myocardial Stunning

Intervention

Drug:
• IV Diazoxide
500 micromoles added to one liter of cardioplegia

Other:
• Placebo
Placebo added to one liter of cardioplegia

Locations

Country	Name	City	State
United States	Johns Hopkins Hospital	Baltimore	Maryland

Sponsors (1)

Lead Sponsor	Collaborator
Johns Hopkins University

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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	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)
Secondary	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
Secondary	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
Secondary	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