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

NCT04830982 | Withdrawn Phase 1 DMC FDA Drug

• 1 other identifier: IRB00265542
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

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.

Conditions

Myocardial Stunning

Outcome Measures

Primary Outcomes (3)

• 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 Outcomes (4)

• Efficacy as assessed by change in ejection fraction

  Day of surgery (pre and post surgery)

• Efficacy as assessed by use of mechanical circulatory support

  48 hours post operatively

• Efficacy as assessed by change in Vasoactive Inotropic Score (VIS)

  0, 24, 48 and 72 hours post operatively

• Efficacy as assessed by time to separate from Cardiopulmonary Bypass (CPB)

  Day of surgery

Study Arms (2)

Diazoxide

EXPERIMENTAL

IV Diazoxide as additive to hypothermic hyperkalemic cardioplegia.

Drug: IV Diazoxide

Placebo

PLACEBO COMPARATOR

Placebo as additive to hypothermic hyperkalemic cardioplegia.

Other: Placebo

Interventions

IV Diazoxide DRUG

500 micromoles added to one liter of cardioplegia

Diazoxide

Placebo OTHER

Placebo added to one liter of cardioplegia

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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

Sponsors & Collaborators

• Johns Hopkins University: lead

Study Sites (1)

Johns Hopkins Hospital

Baltimore, Maryland, 21287, United States

Location

MeSH Terms

Conditions

Myocardial Stunning

Interventions

Diazoxide

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Benzothiadiazines; Sulfonamides; Sulfones; Sulfur Compounds; Organic Chemicals; Thiazides; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Jennifer Lawton, MD

  Johns Hopkins University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 31, 2021
• First Posted: April 5, 2021
• Study Start: September 1, 2023
• Primary Completion: August 30, 2025
• Study Completion: October 30, 2025
• Last Updated: September 19, 2022

Record last verified: 2022-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)