AzTrials
AzTrials

Heart Defects, CongenitalPhase 1NCT02519335

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

A Phase 1 study testing Dexrazoxane in people with Heart Defects, Congenital, run by Medical City Children's Hospital at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 1 day to 6 months
Conditions the study is for
Heart Defects, Congenital
What is being tested?
Dexrazoxane
Could I receive a placebo?
No, everyone receives an active treatment
How many people
12 participants
Where
1 siteUnited States
Study dates
Sep 2014to Mar 2017
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 1 day to 6 months
  • All sexes
  • No healthy volunteers
  • Child

Who may be able to join

  • 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

Who cannot join

  • 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

Trial locations and contacts

1 site in 1 country.

United States1 site
  • Medical City Children's Hospital

    Dallas, Texas, 75230

Other trials in United States

About this study

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.

Read more

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.
Read the detailed description

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.

Being tested
Dexrazoxane
Keywords
cardiopulmonary bypass, ischemia reperfusion injury
Medical subject headings
Heart Defects, Congenital, Reperfusion Injury

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • DexrazoxaneDrug

    Also called Zinecard

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

Study groups in NCT02519335
Study groupRoleWhat they receive
DexrazoxaneOtherTrial 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).
Receives: Drug: Dexrazoxane

What is being measured

The primary outcome is the main question the study is designed to answer.

  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

    Measured: 60 days postoperative

Secondary outcomes (1)
  1. Postoperative low cardiac output syndrome

    observance of clinical signs or symptoms such as tachycardia, oliguria, poor perfusion and cardiac arrest.

    Measured: 60 days

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted10 Aug 2015 (estimated)
  2. Study startSep 2014
  3. Primary completionMar 2017
  4. Study completionMar 2017

Why it stopped: PI no longer at this facility

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
12 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02519335
Sponsor's protocol ID
MCCH-001
Status last verified
Mar 2017
First submitted
14 May 2015
Last updated
26 Jul 2018
Results posted
No
Data monitoring committee
Yes
Individual data sharing
No

Publications

  • Chaney MA. Corticosteroids and cardiopulmonary bypass : a review of clinical investigations. Chest. 2002 Mar;121(3):921-31. doi: 10.1378/chest.121.3.921.

    PubMed 11888978
  • Caputo M, Mokhtari A, Rogers CA, Panayiotou N, Chen Q, Ghorbel MT, Angelini GD, Parry AJ. The effects of normoxic versus hyperoxic cardiopulmonary bypass on oxidative stress and inflammatory response in cyanotic pediatric patients undergoing open cardiac surgery: a randomized controlled trial. J Thorac Cardiovasc Surg. 2009 Jul;138(1):206-14. doi: 10.1016/j.jtcvs.2008.12.028. Epub 2009 Feb 23.

    PubMed 19577081
  • Hare JM. Oxidative stress and apoptosis in heart failure progression. Circ Res. 2001 Aug 3;89(3):198-200. No abstract available.

    PubMed 11485969
  • Pasquali SK, Hall M, Li JS, Peterson ED, Jaggers J, Lodge AJ, Marino BS, Goodman DM, Shah SS. Corticosteroids and outcome in children undergoing congenital heart surgery: analysis of the Pediatric Health Information Systems database. Circulation. 2010 Nov 23;122(21):2123-30. doi: 10.1161/CIRCULATIONAHA.110.948737. Epub 2010 Nov 8.

    PubMed 21060075
  • Graham EM, Atz AM, Butts RJ, Baker NL, Zyblewski SC, Deardorff RL, DeSantis SM, Reeves ST, Bradley SM, Spinale FG. Standardized preoperative corticosteroid treatment in neonates undergoing cardiac surgery: results from a randomized trial. J Thorac Cardiovasc Surg. 2011 Dec;142(6):1523-9. doi: 10.1016/j.jtcvs.2011.04.019. Epub 2011 May 20.

    PubMed 21600592
  • Schroeder VA, Pearl JM, Schwartz SM, Shanley TP, Manning PB, Nelson DP. Combined steroid treatment for congenital heart surgery improves oxygen delivery and reduces postbypass inflammatory mediator expression. Circulation. 2003 Jun 10;107(22):2823-8. doi: 10.1161/01.CIR.0000070955.55636.25. Epub 2003 May 19.

    PubMed 12756159
  • Checchia PA, Backer CL, Bronicki RA, Baden HP, Crawford SE, Green TP, Mavroudis C. Dexamethasone reduces postoperative troponin levels in children undergoing cardiopulmonary bypass. Crit Care Med. 2003 Jun;31(6):1742-5. doi: 10.1097/01.CCM.0000063443.32874.60.

    PubMed 12794414
  • Clarizia NA, Manlhiot C, Schwartz SM, Sivarajan VB, Maratta R, Holtby HM, Gruenwald CE, Caldarone CA, Van Arsdell GS, McCrindle BW. Improved outcomes associated with intraoperative steroid use in high-risk pediatric cardiac surgery. Ann Thorac Surg. 2011 Apr;91(4):1222-7. doi: 10.1016/j.athoracsur.2010.11.005.

    PubMed 21440149
  • Clancy RR, McGaurn SA, Goin JE, Hirtz DG, Norwood WI, Gaynor JW, Jacobs ML, Wernovsky G, Mahle WT, Murphy JD, Nicolson SC, Steven JM, Spray TL. Allopurinol neurocardiac protection trial in infants undergoing heart surgery using deep hypothermic circulatory arrest. Pediatrics. 2001 Jul;108(1):61-70. doi: 10.1542/peds.108.1.61.

    PubMed 11433055
  • Jin Z, Duan W, Chen M, Yu S, Zhang H, Feng G, Xiong L, Yi D. The myocardial protective effects of adenosine pretreatment in children undergoing cardiac surgery: a randomized controlled clinical trial. Eur J Cardiothorac Surg. 2011 May;39(5):e90-6. doi: 10.1016/j.ejcts.2010.12.052. Epub 2011 Feb 20.

    PubMed 21342773
  • Ferreira R, Burgos M, Milei J, Llesuy S, Molteni L, Hourquebie H, Boveris A. Effect of supplementing cardioplegic solution with deferoxamine on reperfused human myocardium. J Thorac Cardiovasc Surg. 1990 Nov;100(5):708-14.

    PubMed 2232833
  • Menasche P, Pasquier C, Bellucci S, Lorente P, Jaillon P, Piwnica A. Deferoxamine reduces neutrophil-mediated free radical production during cardiopulmonary bypass in man. J Thorac Cardiovasc Surg. 1988 Oct;96(4):582-9.

    PubMed 2845199
  • Menasche P, Antebi H, Alcindor LG, Teiger E, Perez G, Giudicelli Y, Nordmann R, Piwnica A. Iron chelation by deferoxamine inhibits lipid peroxidation during cardiopulmonary bypass in humans. Circulation. 1990 Nov;82(5 Suppl):IV390-6.

    PubMed 2225430
  • Zheng H, Dimayuga C, Hudaihed A, Katz SD. Effect of dexrazoxane on homocysteine-induced endothelial dysfunction in normal subjects. Arterioscler Thromb Vasc Biol. 2002 Jul 1;22(7):E15-8. doi: 10.1161/01.atv.0000023187.25914.5b.

    PubMed 12117747
  • Junjing Z, Yan Z, Baolu Z. Scavenging effects of dexrazoxane on free radicals. J Clin Biochem Nutr. 2010 Nov;47(3):238-45. doi: 10.3164/jcbn.10-64. Epub 2010 Oct 29.

    PubMed 21103033

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Dexrazoxane in people with Heart Defects, Congenital, run by Medical City Children's Hospital at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 3 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 26 Jul 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was stopped early (reason given: PI no longer at this facility). Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Resolution of organ failure (time frame: 60 days postoperative). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02519335, which also lists 36 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Jul 2018.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in