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

Primary Purpose

Myocardial Stunning

Status

Withdrawn

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

IV Diazoxide

Placebo

About this trial

This is an interventional prevention trial for Myocardial Stunning

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Johns Hopkins Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Diazoxide

Placebo

Arm Description

IV Diazoxide as additive to hypothermic hyperkalemic cardioplegia.

Placebo as additive to hypothermic hyperkalemic cardioplegia.

Outcomes

Primary Outcome Measures

Safety as assessed by mean change in blood pressure

Mean blood pressure measurements in mmHg.

Safety as assessed by change in blood glucose levels

Blood glucose levels in mg/dl.

Safety as assessed by incidence of adverse events

Safety will be assessed by total number of adverse events.

Secondary Outcome Measures

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

Efficacy as assessed by use of mechanical circulatory support

Incidence of mechanical circulatory support use will be used in the assessment of efficacy.

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).

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.

Full Information

NCT ID

NCT04830982

First Posted

March 31, 2021

Last Updated

September 15, 2022

Sponsor

Johns Hopkins University

1. Study Identification

Unique Protocol Identification Number

NCT04830982

Brief Title

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

2. Study Status

Record Verification Date

September 2022

Overall Recruitment Status

Withdrawn

Why Stopped

Withdrawn in IRB.

Study Start Date

September 1, 2023 (Anticipated)

Primary Completion Date

August 30, 2025 (Anticipated)

Study Completion Date

October 30, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Johns Hopkins University

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Myocardial Stunning

7. Study Design

Primary Purpose

Prevention

Study Phase

Phase 1

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

0 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Diazoxide

Arm Type

Experimental

Arm Description

IV Diazoxide as additive to hypothermic hyperkalemic cardioplegia.

Arm Title

Placebo

Arm Type

Placebo Comparator

Arm Description

Placebo as additive to hypothermic hyperkalemic cardioplegia.

Intervention Type

Drug

Intervention Name(s)

IV Diazoxide

Intervention Description

500 micromoles added to one liter of cardioplegia

Intervention Type

Other

Intervention Name(s)

Placebo

Intervention Description

Placebo added to one liter of cardioplegia

Primary Outcome Measure Information:

Title

Safety as assessed by mean change in blood pressure

Description

Mean blood pressure measurements in mmHg.

Time Frame

From first dose of cardioplegia through 24 hours post operatively

Title

Safety as assessed by change in blood glucose levels

Description

Blood glucose levels in mg/dl.

Time Frame

From first dose of cardioplegia through 48 hours post operatively

Title

Safety as assessed by incidence of adverse events

Description

Safety will be assessed by total number of adverse events.

Time Frame

From first dose of cardioplegia through 7 days post operatively or discharge, whichever comes first

Secondary Outcome Measure Information:

Title

Efficacy as assessed by change in ejection fraction

Description

Comparison of right and left ventricular function (measured as a percentage) on pre and post operative Transesophageal echocardiograms

Time Frame

Day of surgery (pre and post surgery)

Title

Efficacy as assessed by use of mechanical circulatory support

Description

Incidence of mechanical circulatory support use will be used in the assessment of efficacy.

Time Frame

48 hours post operatively

Title

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

Description

Comparison of VIS Score with values from 0 to >45, with lower scores indicating medication efficacy (0e5, >5e15, >15e30, >30e45, and >45 points).

Time Frame

0, 24, 48 and 72 hours post operatively

Title

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

Description

From time of first turn down of CPB to CPB end time measured in minutes.

Time Frame

Day of surgery

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Jennifer Lawton, MD

Organizational Affiliation

Johns Hopkins University

Official's Role

Principal Investigator

Facility Information:

Facility Name

Johns Hopkins Hospital

City

Baltimore

State/Province

Maryland

ZIP/Postal Code

21287

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

Learn more about this trial

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

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