Here is the design of a clinical trial:

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

Included conditions:
- Congenital Heart Disease in Children
- Neuroprotection

Study Armgroups:
- {'label': 'Allopurinol', 'type': 'ACTIVE_COMPARATOR', 'interventionNames': ['Drug: Allopurinol']}
- {'label': 'Placebo', 'type': 'PLACEBO_COMPARATOR', 'interventionNames': ['Drug: Mannitol']}

Interventions:
- {'type': 'DRUG', 'name': 'Allopurinol', 'description': '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.', 'armGroupLabels': ['Allopurinol']}
- {'type': 'DRUG', 'name': 'Mannitol', 'description': '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.', 'armGroupLabels': ['Placebo']}

Primary Outcomes:
- {'measure': 'Relevant parenchymatous brain injury on postoperative MRI', 'description': 'The presence or absence of relevant (moderate/severe) parenchymatous (ischemic or hemorrhagic) brain injury on postoperative MRI will be assessed, using the T1/T2/DWI and SWI weighted images.', 'timeFrame': 'between birth and 1 month after cardiac surgery'}
- {'measure': "Rate of children that are considered 'too unstable for postoperative MRI'", 'description': 'This decision is based on the circulatory and respiratory status of the child before the planned postoperative MRI, as included in local guidelines (not part of this protocol) of each participating center.', 'timeFrame': 'between birth and 1 month after cardiac surgery'}
- {'measure': 'Incidence of mortality', 'description': 'Defined as death until one month postoperatively.', 'timeFrame': 'between birth and 1 month after cardiac surgery'}

Please estimate the sample size based on the assumption: 
80% power, two-sided alpha of 5%, hierarchical testing strategy, and rare occurrence of participant substitution due to unexpected non-requirement of cardiac surgery or consent withdrawal.
Sample size
          The sample size is calculated based on an assumed reduction in (absolute) incidence of 20% in the more prevalent subgroup of prenatal diagnosis (Â± 80% of the total population, control event rate assumed 71%) and a reduction of 9% in the postnatal diagnosis group (Â± 20% of the population, control event rate assumed 55%). With a total sample size of 236 CCHD neonates, of which 188 in the prenatal subgroup and 48 in the postnatal subgroup, the study has approximately 80% power to demonstrate the advantage of allopurinol in the total group with a two-sided alpha of 5%. The power of the hierarchical testing strategy is only slightly affected, given the large proportion of the prenatal group (80%). The effect sizes are a relevant and viable expectation and are based on the results of previous neuroprotective studies on head cooling in neonatal encephalopathy and perioperative allopurinol administration in CCHD neonates [26, 59]. RStudio version 3.6.1 was used for the sample size analysis.
          Participants will be substituted in the following cases: (1) when cardiac surgery with CPB in the first month of life is unexpectedly not required or (2) when there is consent withdrawal before postoperative MRI. It is to be expected that these cases rarely occur.