Use of the Cardioprotectant Dexrazoxane During Congenital Heart Surgery: Proposal for Pilot Investigation

NCT02519335 | Terminated Phase 1 DMC

• 1 other identifier: MCCH-001
• 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. Therefore, the investigators are performing a pilot study of 12 children to assess:

1. 1.how Dexrazoxane at 3 different doses is metabolized in the body of a child age 0-6 months during and after congenital heart surgery, and
2. 2.the safety of Dexrazoxane use in the neonatal and young infant population undergoing cardiac surgery.

Conditions

Heart Defects, Congenital

Keywords

cardiopulmonary bypass; ischemia reperfusion injury

Outcome Measures

Primary Outcomes (1)

• Resolution of organ failure

  measured by number of days to the point of being off invasive mechanical ventilation, renal replacement therapy and inotropic support

  60 days postoperative

Secondary Outcomes (1)

• Postoperative low cardiac output syndrome

  60 days

Other Outcomes (6)

• Myocardial injury

  60 days

• Oxidative stress

  60 days

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

  60 days

Study Arms (1)

Dexrazoxane

OTHER

Trial subjects will be assigned preoperatively to receive Dexrazoxane at one of three doses: low (200mg/m2/dose), medium (300mg/m2/dose), or high (400mg/m2/dose). Four patients will be assigned to each dosing regimen for a total of 12 patients. The medication will be administered in the operating room 15-30 minutes prior to starting cardiopulmonary bypass (dose #1), after finishing cardiopulmonary bypass (dose #2), and on the morning after surgery in the cardiac intensive care unit (dose #3).

Drug: Dexrazoxane

Interventions

Dexrazoxane DRUG

Dose escalation every 4 subjects from 200mg/m2/dose; 300mg/m2/dose to 400mg/m2/dose

Also known as: Zinecard

Dexrazoxane

Eligibility Criteria

• Age: 1 Day - 6 Months
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• age 6 months and under
• open heart surgery requiring CPB and use of cardioplegia
• parent/guardian consent for study obtained surgery planned Monday to Friday

You may not qualify if:

• gestational age \<36weeks
• known syndrome or genetic abnormality, except Trisomy 21 single ventricle physiology
• concurrent enrollment in another research protocol
• no parental/guardian consent obtained
• ECMO utilization prior to surgery or necessary at the time of ICU admission

Sponsors & Collaborators

• Medical City Children's Hospital: lead
• Mylan Pharmaceuticals Inc: collaborator

Study Sites (1)

Medical City Children's Hospital

Dallas, Texas, 75230, United States

Location

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MeSH Terms

Conditions

Heart Defects, Congenital; Reperfusion Injury

Interventions

Dexrazoxane

Condition Hierarchy (Ancestors)

Cardiovascular Abnormalities; Cardiovascular Diseases; Heart Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Vascular Diseases; Postoperative Complications; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

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

Study Officials

• Daniel Stromberg, MD

  Medical City Children's Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 14, 2015
• First Posted: August 10, 2015
• Study Start: September 1, 2014
• Primary Completion: March 1, 2017
• Study Completion: March 1, 2017
• Last Updated: July 26, 2018

Record last verified: 2017-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)