Myocardial Stunning
Conditions
Brief 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.
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.
Interventions
DRUGIV Diazoxide
500 micromoles added to one liter of cardioplegia
OTHERPlacebo
Placebo added to one liter of cardioplegia
Sponsors
Johns Hopkins University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety as assessed by mean change in blood pressure | From first dose of cardioplegia through 24 hours post operatively | Mean blood pressure measurements in mmHg. |
| Safety as assessed by change in blood glucose levels | From first dose of cardioplegia through 48 hours post operatively | Blood glucose levels in mg/dl. |
| Safety as assessed by incidence of adverse events | From first dose of cardioplegia through 7 days post operatively or discharge, whichever comes first | Safety will be assessed by total number of adverse events. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Efficacy as assessed by change in ejection fraction | Day of surgery (pre and post surgery) | Comparison of right and left ventricular function (measured as a percentage) on pre and post operative Transesophageal echocardiograms |
| Efficacy as assessed by time to separate from Cardiopulmonary Bypass (CPB) | Day of surgery | From time of first turn down of CPB to CPB end time measured in minutes. |
| Efficacy as assessed by use of mechanical circulatory support | 48 hours post operatively | Incidence of mechanical circulatory support use will be used in the assessment of efficacy. |
| Efficacy as assessed by change in Vasoactive Inotropic Score (VIS) | 0, 24, 48 and 72 hours post operatively | Comparison of VIS Score with values from 0 to \>45, with lower scores indicating medication efficacy (0e5, \>5e15, \>15e30, \>30e45, and \>45 points). |
Countries
United States
Outcome results
None listed