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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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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

Conditions
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Myocardial Stunning

Intervention / Treatment
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* Drug: IV Diazoxide
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Diazoxide<br>IV Diazoxide as additive to hypothermic hyperkalemic cardioplegia. | Drug: IV Diazoxide<br>* 500 micromoles added to one liter of cardioplegia<br>|
| Placebo Comparator: Placebo<br>Placebo as additive to hypothermic hyperkalemic cardioplegia. | Other: Placebo<br>* Placebo added to one liter of cardioplegia<br>|

What is the study measuring?
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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 |