Use of the Cardioprotectant Dexrazoxane During Congenital Heart Surgery

NCT04997291 | Unknown Phase 1 DMC FDA Drug

• 1 other identifier: 2020-02-0075
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Heart Defects, Congenital

Outcome Measures

Primary Outcomes (4)

• Peak Plasma Concentration (Cmax)

  24 hours

• Area under the plasma concentration vs time curve (AUC)

  24 hours

• Minimum plasma concentration (Cmin)

  24 hours

• Time to resolution of organ failure

  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 Outcomes (10)

• Myocardial Injury

  7 days

• Oxidative Stress

  3 days

• Inflammatory activation (IL-6 and IL-10)

  3 days

• Neurologic IR injury

  3 days

• ICU Length of Stay

  60 days

Study Arms (1)

Dexrazoxane

EXPERIMENTAL

Drug: Dexrazoxane

Interventions

Dexrazoxane DRUG

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).

Also known as: Zinecard

Dexrazoxane

Eligibility Criteria

• Age: 0 Years - 1 Year
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Texas at Austin: lead
• Dell Children's Medical Center of Central Texas: collaborator

Study Sites (1)

Dell Children's Medical Center of Central Texas

Austin, Texas, 78723, United States

RECRUITING

Related Publications (46)

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MeSH Terms

Conditions

Heart Defects, Congenital

Interventions

Dexrazoxane

Condition Hierarchy (Ancestors)

Cardiovascular Abnormalities; Cardiovascular Diseases; Heart Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Razoxane; Diketopiperazines; Piperazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Central Study Contacts

Daniel Stromberg, MD

CONTACT

512-324-3357; dstromberg@austin.utexas.edu

Jacob Strelow, MPH

CONTACT

757-268-2691; strelow.jacob@austin.utexas.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: July 21, 2021
• First Posted: August 9, 2021
• Study Start: April 9, 2021
• Primary Completion: October 1, 2021
• Study Completion: January 1, 2022
• Last Updated: August 9, 2021

Record last verified: 2021-08

Locations

US (1)