Use of the Cardioprotectant Dexrazoxane During Congenital Heart Surgery: Proposal for Pilot Investigation
| Status: | Terminated |
|---|---|
| Conditions: | Cardiology, Women's Studies |
| Therapuetic Areas: | Cardiology / Vascular Diseases, Reproductive |
| Healthy: | No |
| Age Range: | Any |
| Updated: | 7/28/2018 |
| Start Date: | September 2014 |
| End Date: | March 2017 |
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. 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. the safety of Dexrazoxane use in the neonatal and young infant population undergoing
cardiac surgery.
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. 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. the safety of Dexrazoxane use in the neonatal and young infant population undergoing
cardiac surgery.
Neonates and infants undergoing heart surgery with 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 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 deleterious effects of cardiopulmonary bypass [CPB] with cardioplegic arrest of the heart
during congenital heart operations greatly influence postoperative morbidity and mortality.
Neonates and infants undergoing cardiac surgery experience both a systemic inflammatory
response, and myocardial IR injury as cardioplegic arrest is reversed. These processes
provoke elaboration of cytokines and activation of the complement cascade, as well as oxygen
free radical formation and induction of myocardial apoptosis (1, 2, 3). Frequently,
myocardial injury and cardiac dysfunction ensue, leading to low cardiac output syndrome and
multi-system organ failure. The irreversible component of these injuries, in addition to the
abnormal workloads imposed on the myocardium from the anatomic defects themselves, may have
consequences for long-term cardiac function, and may in part explain contractile dysfunction
observed late after congenital heart
The investigators propose a pilot pharmacokinetic/safety trial of dexrazoxane in children 0-6
months of age, followed by a randomized, double-blind, clinical trial of dexrazoxane vs
placebo during congenital heart surgery. The investigators will evaluate postoperative time
to resolution of organ failure, development of low cardiac output syndrome, length of cardiac
ICU and hospital stays, and echocardiographic indices of cardiac dysfunction. Results could
establish the safety and clinical utility of dexrazoxane in ameliorating ischemia-reperfusion
injury during congenital heart surgery.
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 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 deleterious effects of cardiopulmonary bypass [CPB] with cardioplegic arrest of the heart
during congenital heart operations greatly influence postoperative morbidity and mortality.
Neonates and infants undergoing cardiac surgery experience both a systemic inflammatory
response, and myocardial IR injury as cardioplegic arrest is reversed. These processes
provoke elaboration of cytokines and activation of the complement cascade, as well as oxygen
free radical formation and induction of myocardial apoptosis (1, 2, 3). Frequently,
myocardial injury and cardiac dysfunction ensue, leading to low cardiac output syndrome and
multi-system organ failure. The irreversible component of these injuries, in addition to the
abnormal workloads imposed on the myocardium from the anatomic defects themselves, may have
consequences for long-term cardiac function, and may in part explain contractile dysfunction
observed late after congenital heart
The investigators propose a pilot pharmacokinetic/safety trial of dexrazoxane in children 0-6
months of age, followed by a randomized, double-blind, clinical trial of dexrazoxane vs
placebo during congenital heart surgery. The investigators will evaluate postoperative time
to resolution of organ failure, development of low cardiac output syndrome, length of cardiac
ICU and hospital stays, and echocardiographic indices of cardiac dysfunction. Results could
establish the safety and clinical utility of dexrazoxane in ameliorating ischemia-reperfusion
injury during congenital heart surgery.
Inclusion Criteria:
- 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
Exclusion Criteria:
- 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
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