Clinical trial NCT04997291: Use of the Cardioprotectant Dexrazoxane During Congenital Heart Surgery
Official title: Use of the Cardioprotectant Dexrazoxane During Congenital Heart Surgery
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
Conditions: Heart Defects, Congenital
Lead sponsor: University of Texas at Austin
Sponsor class: OTHER
Collaborators: name: Dell Children's Medical Center of Central Texas
First posted: 2021-08-09
Enrollment: 12
Sex: ALL
Minimum age (years): 0
Maximum age (years): 1
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Peak Plasma Concentration (Cmax)
timeFrame: 24 hours
measure: Area under the plasma concentration vs time curve (AUC)
timeFrame: 24 hours
measure: Minimum plasma concentration (Cmin)
timeFrame: 24 hours
measure: Time to resolution of organ failure
timeFrame: 14 days
Secondary outcomes:
measure: Myocardial Injury
timeFrame: 7 days
measure: Oxidative Stress
timeFrame: 3 days
measure: Inflammatory activation (IL-6 and IL-10)
timeFrame: 3 days
measure: Neurologic IR injury
timeFrame: 3 days
measure: ICU Length of Stay
timeFrame: 60 days
measure: Hospital Length of Stay
timeFrame: 60 days
measure: Tei Index (via echocardiogram)
timeFrame: 60 days
measure: Ventricular ejection fraction (via echocardiogram)
timeFrame: 60 days
measure: Tissue doppler E/E' ratio (via echocardiogram)
timeFrame: 60 days
measure: Composite outcome for neonatal cardiac surgery
timeFrame: 60 days
Other outcomes:
Locations:
city: Austin
country: United States
facility: Dell Children's Medical Center of Central Texas
state: Texas
Study officials:
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