Clinical trial NCT04830982: Safety and Efficacy of IV Diazoxide as an Additive to Hyperkalemic Cardioplegia in Patients Undergoing Cardiac Surgery With Cardiopulmonary Bypass
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
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE1
Conditions: Myocardial Stunning
Lead sponsor: Johns Hopkins University
Sponsor class: OTHER
First posted: 2021-04-05
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

Eligibility criteria: 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

Primary outcomes:
measure: Safety as assessed by mean change in blood pressure
timeFrame: From first dose of cardioplegia through 24 hours post operatively
measure: Safety as assessed by change in blood glucose levels
timeFrame: From first dose of cardioplegia through 48 hours post operatively
measure: Safety as assessed by incidence of adverse events
timeFrame: From first dose of cardioplegia through 7 days post operatively or discharge, whichever comes first
Secondary outcomes:
measure: Efficacy as assessed by change in ejection fraction
timeFrame: Day of surgery (pre and post surgery)
measure: Efficacy as assessed by use of mechanical circulatory support
timeFrame: 48 hours post operatively
measure: Efficacy as assessed by change in Vasoactive Inotropic Score (VIS)
timeFrame: 0, 24, 48 and 72 hours post operatively
measure: Efficacy as assessed by time to separate from Cardiopulmonary Bypass (CPB)
timeFrame: Day of surgery
Other outcomes:
Locations:
city: Baltimore
country: United States
facility: Johns Hopkins Hospital
state: Maryland
Study officials:
affiliation: Johns Hopkins University
name: Jennifer Lawton, MD
role: PRINCIPAL_INVESTIGATOR
References: