Use of the Cardioprotectant Dexrazoxane During Congenital Heart Surgery

August 2, 2021 updated by: Daniel Stromberg, University of Texas at Austin

Cardiopulmonary bypass and arrest of the heart during cardiac surgery are necessary to allow the surgeon to perform heart operations. However, these processes can cause injury to the heart which may worsen post-operative outcomes. In fact, the effects of these injuries may continue after surgery, and lead to a long-term decrease in heart function. Neonates and young infants are at particular risk for this occurrence.

While much research has been done in adults looking for medicines that might protect the heart during surgery, few studies have been conducted in neonates and young infants. The investigators are testing Dexrazoxane, which has proven to be cardio-protective in pediatric cancer patients, in the hope that it may lessen cardiac injury during and after congenital heart surgery, and thereby improve outcomes in the neonatal and young infant population.

In order to accomplish this, the investigators must first determine how Dexrazoxane can be safely administered to young children with congenital heart disease.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Neonates and infants undergoing heart surgery with cardiopulmonary bypass and cardioplegic arrest experience both inflammation and myocardial ischemia-reperfusion [IR] injury. These processes provoke myocardial apoptosis and oxygen free radical formation which result in cardiac injury and dysfunction. Dexrazoxane [DRZ] is a derivative of EDTA that is approved for prevention of anthracycline-related cardiotoxicity. It provides cardioprotection through reduction of toxic reactive oxygen species [ROS], and suppression of apoptosis.

The investigators propose a 12-patient pilot to determine DRZ pharmacokinetics, and to collect additional safety data in the neonatal and infant population. Efficacy of cardioprotection will not be evaluated in this preliminary investigation, though the investigators will determine postoperative time to resolution of organ failure, development of low cardiac output syndrome, length of cardiac ICU and hospital stays, laboratory indices of myocardial injury and systemic inflammation, and echocardiographic cardiac dysfunction for safety purposes, and as a run-in to the larger, randomized, placebo controlled trial. Conducting this pilot could optimize team execution of the study protocol. In addition, results could further establish the safety of DRZ in the neonatal and infant populations.

Study Type

Interventional

Enrollment (Anticipated)

12

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • United States
    • Texas
      • Austin, Texas, United States, 78723
        • Recruiting
        • Dell Children's Medical Center of Central Texas

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

1 second to 1 year (Child)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • age ≤ 1 year
  • open heart surgery requiring CPB and use of cardioplegia
  • parent/guardian consent for study obtained
  • surgery planned Monday-Friday

Exclusion Criteria:

  • gestational age <36 weeks at time of enrollment
  • known syndrome or genetic abnormality, except Trisomy 21
  • single ventricle physiology
  • concurrent enrollment in another research protocol

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Dexrazoxane
Drug: Dexrazoxane
Twelve enrollees will be consecutively assigned to a dosing regimen of 400 mg/m2/dose. The medication will be administered in the operating room 30 minutes prior to starting cardiopulmonary bypass (dose #1), prior to aortic cross clamp removal (dose #2), and on the morning after surgery in the cardiac intensive care unit (dose #3).
Other Names:
  • Zinecard

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Peak Plasma Concentration (Cmax)
Time Frame: 24 hours
24 hours
Area under the plasma concentration vs time curve (AUC)
Time Frame: 24 hours
24 hours
Minimum plasma concentration (Cmin)
Time Frame: 24 hours
24 hours
Time to resolution of organ failure
Time Frame: 14 days
defined as hours to the point of being off invasive mechanical ventilation, without significant renal dysfunction [cystatin C within normal range for age, and UOP > 1 cc/kg/hr], and off significant inotropic support [defined as milrinone >0.3 mcg/kg/min, dopamine >3 mcg/kg/min, dobutamine >3 mcg/kg/min, any combination of these inotropes, or any epinephrine, norepinephrine, phenylephrine or vasopressin)] with a serum lactate <2 mmol/L. One point will be awarded for each postoperative hour of continued organ dysfunction up to postoperative hour 336 (day 14). A score of 360 will be assigned if organ failure is not resolved by postoperative day 14, or if the patient requires mechanical circulatory support or experiences mortality. This variable has been chosen to allow for recognition of early drug effects, and those which might be delayed beyond the immediate postoperative period.
14 days

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Myocardial Injury
Time Frame: 7 days
determined by elevated serum cardiac troponin
7 days
Oxidative Stress
Time Frame: 3 days
measured by lipoperoxidation (serum F2 isoprostane)
3 days
Inflammatory activation (IL-6 and IL-10)
Time Frame: 3 days
3 days
Neurologic IR injury
Time Frame: 3 days
measured by serum activin A concentration
3 days
ICU Length of Stay
Time Frame: 60 days
60 days
Hospital Length of Stay
Time Frame: 60 days
60 days
Tei Index (via echocardiogram)
Time Frame: 60 days
the sum of the isovolumic contraction and relaxation times divided by the ejection time
60 days
Ventricular ejection fraction (via echocardiogram)
Time Frame: 60 days
the volumetric fraction of fluid ejected from a chamber with each contraction
60 days
Tissue doppler E/E' ratio (via echocardiogram)
Time Frame: 60 days
calculated as E wave divided by e' velocities
60 days
Composite outcome for neonatal cardiac surgery
Time Frame: 60 days
(per Graham, EM, et al) - binary variable defined as death, use of mechanical circulatory support, cardiac arrest requiring chest compressions, hepatic injury [2 times the upper limit of normal for AST or ALT], renal injury [Cr >1.5 mg/dL], or lactic acidosis [an increasing lactate >5 mmol/L in the postoperative period]
60 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Texas at Austin

Collaborators

Dell Children's Medical Center of Central Texas

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

April 9, 2021

Primary Completion (Anticipated)

October 1, 2021

Study Completion (Anticipated)

January 1, 2022

Study Registration Dates

First Submitted

July 21, 2021

First Submitted That Met QC Criteria

August 2, 2021

First Posted (Actual)

August 9, 2021

Study Record Updates

Last Update Posted (Actual)

August 9, 2021

Last Update Submitted That Met QC Criteria

August 2, 2021

Last Verified

August 1, 2021

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2020-02-0075

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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