The effect of allopurinol on the reduction of brain injury in neonates with severe congenital heart disease

Conditions

Brain injury in neonates with critical congenital heart disease requiring cardiac surgery with cardiopulmonary bypass. MedDRA version: 20.0 Level: LLT Classification code 10010495 Term: Congenital heart disease NOS System Organ Class: 100000004850 MedDRA version: 20.0 Level: PT Classification code 10067967 Term: Brain injury System Organ Class: 10029205 - Nervous system disorders

Chu WY, Nijman M, Stegeman R, Breur JMPJ, Jansen NJG, Nijman J, van Loon K, Koomen E, Allegaert K, Benders MJNL, Dorlo TPC, Huitema ADR, CRUCIAL trial consortium.

2024-08-151 citations

10.1007/s40262-024-01401-3

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.

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.

2022-02-239 citations

10.1186/s13063-022-06098-y

Interventions

Trade Name: ACEPURIN Product Name: Allokid Pharmaceutical Form: Powder for solution for infusion INN or Proposed INN: Allopurinol sodium CAS Number: 17795-21-0 Other descriptive name: ALLOPURINOL SOD

Eligibility

Sex/Gender

All

Inclusion criteria

Inclusion criteria: Neonates with a prenatally (before birth) or postnatally (after birth) confirmed diagnosis of critical congenital heart disease requiring (anticipated) cardiac surgery with cardiopulmonary bypass (within the first 4 weeks of life). Are the trial subjects under 18? yes Number of subjects for this age range: 236 F.1.2 Adults (18-64 years) no F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range

Exclusion criteria

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. - Gestational age below 36 weeks and/or birth weight less than 2000 gram. - Surgery not requiring cardiopulmonary bypass. - Patient considered “moribund”. - Decision for “comfort care only”.

Design outcomes

Primary

Measure	Time frame
Main Objective: To evaluate whether in newborns with critical congenital heart disease, early postnatal (after birth) and perioperative (around cardiac surgery with cardiopulmonary bypass) allopurinol compared to placebo (mannitol) administration reduces relevant (moderate/severe) parenchymatous brain injury on postoperative MRI. ;Secondary Objective: To evaluate the effect of allopurinol on: - Brain injury severity score and volume of hypoxic-ischemic injury (MRI). - Brain function (amplitude integrated electroenchepalogram) and oxygenation (near-infrared spectroscopy). - Cardiac function (echocardiography). - Neurodevelopmental outcome (general movements, Bayley scales of infant development and executive functioning). - Quality of life. - Cost-effectiveness of allopurinol. ;Primary end point(s): Primary outcome is a composite endpoint of relevant (moderate/severe) parenchymatous brain injury on postoperative MRI or too instable for postoperative MRI or mortality ;Timepoint(s) of evaluation of this end point: Primary endpoint will be measured at postoperative MRI. The postoperative MRI takes place 5 to 10 days (and at least within 1 month) after cardiac surgery with cardiopulmonary bypass, which is usually within the neonatal period (first month of life).	—

Measure

Time frame

Main Objective: To evaluate whether in newborns with critical congenital heart disease, early postnatal (after birth) and perioperative (around cardiac surgery with cardiopulmonary bypass) allopurinol compared to placebo (mannitol) administration reduces relevant (moderate/severe) parenchymatous brain injury on postoperative MRI. ;Secondary Objective: To evaluate the effect of allopurinol on: - Brain injury severity score and volume of hypoxic-ischemic injury (MRI). - Brain function (amplitude integrated electroenchepalogram) and oxygenation (near-infrared spectroscopy). - Cardiac function (echocardiography). - Neurodevelopmental outcome (general movements, Bayley scales of infant development and executive functioning). - Quality of life. - Cost-effectiveness of allopurinol. ;Primary end point(s): Primary outcome is a composite endpoint of relevant (moderate/severe) parenchymatous brain injury on postoperative MRI or too instable for postoperative MRI or mortality ;Timepoint(s) of evaluation of this end point: Primary endpoint will be measured at postoperative MRI. The postoperative MRI takes place 5 to 10 days (and at least within 1 month) after cardiac surgery with cardiopulmonary bypass, which is usually within the neonatal period (first month of life).

—

Secondary

Measure	Time frame
Secondary end point(s): Secondary outcome measures are: - Brain injury severity score and volume of hypoxic-ischemic brain injury (pre- and postoperative MRI) - Brain function: background pattern and seizure activity (postnatal and perioperative amplitude integrated electroenchepalogram). - Brain oxygenation (postnatal and perioperative near-infrared spectroscopy). - Cardiac function (pre- and postoperative echocardiography). - Neurodevelopmental outcome (general movements at 3 months and Bayley scales of infant development and executive functioning testing at 24 months). - Quality of Life (TNO-TAPQOL at 24 months). - Cost-effectiveness of allopurinol (questionnaires during hospital stay, at 3 and 24 months). - Pharmacokinetics of allopurinol (substudy: postnatally, perioperatively). ;Timepoint(s) of evaluation of this end point: Timepoints of each endpoint evaluation are mentioned in E.5.2. All endpoints will be expected within the neonatal period (first month of life) except neurodevelopmental outcome assessment and quality of life and cost-effectiveness questionnaires which takes place (also) at 3 and 24 months of age.	—

Measure

Time frame

Secondary end point(s): Secondary outcome measures are: - Brain injury severity score and volume of hypoxic-ischemic brain injury (pre- and postoperative MRI) - Brain function: background pattern and seizure activity (postnatal and perioperative amplitude integrated electroenchepalogram). - Brain oxygenation (postnatal and perioperative near-infrared spectroscopy). - Cardiac function (pre- and postoperative echocardiography). - Neurodevelopmental outcome (general movements at 3 months and Bayley scales of infant development and executive functioning testing at 24 months). - Quality of Life (TNO-TAPQOL at 24 months). - Cost-effectiveness of allopurinol (questionnaires during hospital stay, at 3 and 24 months). - Pharmacokinetics of allopurinol (substudy: postnatally, perioperatively). ;Timepoint(s) of evaluation of this end point: Timepoints of each endpoint evaluation are mentioned in E.5.2. All endpoints will be expected within the neonatal period (first month of life) except neurodevelopmental outcome assessment and quality of life and cost-effectiveness questionnaires which takes place (also) at 3 and 24 months of age.

—

Countries

Netherlands

Contacts

Public ContactClinical Trial Information Desk

Wilhelmina Children's Hospital

+31646919545

Outcome results

None listed