Cerebrum and Cardiac Protection With Allopurinol in Neonates With Critical Congenital Heart Disease Requiring Cardiac Surgery With Cardiopulmonary Bypass

NCT ID: NCT04217421

Last Updated: 2024-05-16

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE3

Total Enrollment

236 participants

Study Classification

INTERVENTIONAL

Study Start Date

2020-02-14

Study Completion Date

2028-12-31

Brief Summary

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Neurodevelopmental impairment due to delayed brain development and brain injury is a fundamental problem in children with critical congenital heart disease (CCHD). Significant longterm motor-, cognitive-, and behavioral problems are the result of early postnatally and perioperatively induced brain injury. Allopurinol, a xanthine oxidase inhibitor, prevents the formation of toxic free oxygen radicals, thereby limiting hypoxia-reperfusion damage. Both animal and neonatal studies suggest that administration of allopurinol reduces hypoxic-ischemic brain injury, is cardioprotective, and safe. This study aims to evaluate the efficacy and safety of allopurinol administered early postnatally and perioperatively in children with a CCHD requiring cardiac surgery with cardiopulmonary bypass.

Detailed Description

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Conditions

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Congenital Heart Disease in Children Neuroprotection

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Allopurinol

Group Type ACTIVE_COMPARATOR

Allopurinol

Intervention Type DRUG

Allopurinol powder for solution for infusion (PFI) 20 mg/kg body weight per administration will be administered early postnatally (within 45 minutes and 12 hours after the first dose), preoperatively (12 hours before surgery), intraoperatively (during surgery) and postoperatively (24 hours after surgery) to the neonate in case of a prenatal CCHD diagnosis. Allopurinol PFI will be administered only pre-, intra- and postoperatively to the neonate in case of a postnatal CCHD diagnosis.

Placebo

Group Type PLACEBO_COMPARATOR

Mannitol

Intervention Type DRUG

Mannitol powder for solution (PFI) placebo will be administered early postnatally (within 45 minutes and 12 hours after birth), preoperatively (12 hours before surgery), intraoperatively (during surgery), and postoperatively (24 hours after surgery) to the neonate in case of a prenatal CCHD diagnosis. Mannitol PFI-placebo will be administered only pre-, intra- and postoperatively to the neonate in case of a postnatal CCHD diagnosis.

Interventions

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Allopurinol

Allopurinol powder for solution for infusion (PFI) 20 mg/kg body weight per administration will be administered early postnatally (within 45 minutes and 12 hours after the first dose), preoperatively (12 hours before surgery), intraoperatively (during surgery) and postoperatively (24 hours after surgery) to the neonate in case of a prenatal CCHD diagnosis. Allopurinol PFI will be administered only pre-, intra- and postoperatively to the neonate in case of a postnatal CCHD diagnosis.

Intervention Type DRUG

Mannitol

Mannitol powder for solution (PFI) placebo will be administered early postnatally (within 45 minutes and 12 hours after birth), preoperatively (12 hours before surgery), intraoperatively (during surgery), and postoperatively (24 hours after surgery) to the neonate in case of a prenatal CCHD diagnosis. Mannitol PFI-placebo will be administered only pre-, intra- and postoperatively to the neonate in case of a postnatal CCHD diagnosis.

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* Neonates with a prenatally or postnatally confirmed diagnosis of CCHD requiring (anticipated) cardiac surgery with CPB within the first 4 weeks of life.
* Informed consent provided by both parents.

Exclusion Criteria

* Inability to enroll the patient before the start of delivery in case of prenatal diagnosis, or 24 hours before surgery in case of postnatal diagnosis.
* Doubt whether the aortic arch anomaly before birth requires cardiac surgery with CPB in the neonatal period.
* Gestational age below 36 weeks and/or birth weight less than 2000 gram.
* Surgery not requiring cardiopulmonary bypass.
* Decision for "comfort care only".
Maximum Eligible Age

1 Month

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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ZonMw: The Netherlands Organisation for Health Research and Development

OTHER

Sponsor Role collaborator

University Medical Center Groningen

OTHER

Sponsor Role collaborator

Erasmus Medical Center

OTHER

Sponsor Role collaborator

University Medical Center Nijmegen

OTHER

Sponsor Role collaborator

ACE Pharmaceuticals BV

OTHER

Sponsor Role collaborator

dr. M.J.N.L. Benders

OTHER

Sponsor Role lead

Responsible Party

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dr. M.J.N.L. Benders

Professor, Head of Neonatology, MD

Responsibility Role SPONSOR_INVESTIGATOR

Principal Investigators

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Manon JNL Benders, Prof. MD PhD

Role: PRINCIPAL_INVESTIGATOR

University Medical Center Utrecht (UMC Utrecht)

Johannes (Hans) MPJ Breur, MD PhD

Role: PRINCIPAL_INVESTIGATOR

University Medical Center Utrecht (UMC Utrecht)

Nicolaas (Koos) JG Jansen, MD PhD

Role: STUDY_DIRECTOR

University Medical Center Utrecht (UMC Utrecht)

Raymond Stegeman, MD

Role: STUDY_DIRECTOR

University Medical Center Utrecht (UMC Utrecht)

Locations

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University Medical Center Groningen (UMCG)

Groningen, , Netherlands

Site Status RECRUITING

Radboud University Medical Center Nijmegen (Radboudumc)

Nijmegen, , Netherlands

Site Status ACTIVE_NOT_RECRUITING

Erasmus Medical Center Rotterdam (Erasmus MC)

Rotterdam, , Netherlands

Site Status RECRUITING

University Medical Center Utrecht (UMC Utrecht)

Utrecht, , Netherlands

Site Status RECRUITING

Countries

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Netherlands

Central Contacts

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Manon JNL Benders, Prof. MD PhD

Role: CONTACT

0031887554545

Maaike Nijman, MD

Role: CONTACT

Facility Contacts

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Arend F Bos, Prof. MD PhD

Role: primary

Nicolaas (Koos) JG Jansen, MD PhD

Role: backup

Ingrid M van Beynum, MD PhD

Role: primary

Manon JNL Benders, Prof. MD PhD

Role: primary

Maaike Nijman, MD

Role: backup

References

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Stegeman R, Nijman M, Breur JMPJ, Groenendaal F, Haas F, Derks JB, Nijman J, van Beynum IM, Taverne YJHJ, Bogers AJJC, Helbing WA, de Boode WP, Bos AF, Berger RMF, Accord RE, Roes KCB, de Wit GA, Jansen NJG, Benders MJNL; CRUCIAL trial consortium. CeRebrUm and CardIac Protection with ALlopurinol in Neonates with Critical Congenital Heart Disease Requiring Cardiac Surgery with Cardiopulmonary Bypass (CRUCIAL): study protocol of a phase III, randomized, quadruple-blinded, placebo-controlled, Dutch multicenter trial. Trials. 2022 Feb 23;23(1):174. doi: 10.1186/s13063-022-06098-y.

Reference Type BACKGROUND
PMID: 35197082 (View on PubMed)

Other Identifiers

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2017-004596-31

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

METC UMCU 18-791

Identifier Type: -

Identifier Source: org_study_id

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