Here is the design of a clinical trial:

Official Title: Effect of ALlopurinol in Addition to Hypothermia for Hypoxic-ischemic Brain Injury on Neurocognitive Outcome - a Blinded Randomized Placebo-controlled Parallel Group Multicenter Trial for Superiority (Phase III)

Included conditions:
- Encephalopathy, Hypoxic-Ischemic
- Infant, Newborn, Diseases

Study Armgroups:
- {'label': 'Allopurinol', 'type': 'ACTIVE_COMPARATOR', 'description': 'Allopurinol, powder for injection (PFI), administered in two doses. First dose (20 mg/kg in 2ml/kg sterile water for injection) given as soon as intravenous access is established and no later than 30min postnatally and second dose (10mg/kg in 1ml/kg sterile water for injection) 12 hours thereafter. The second dose will only be administered to in infants on therapeutic hypothermia. Infants who recover quickly and do not qualify for and hence do not undergo hypothermia will not receive a second dose. Administration will be by continuous infusion using a syringe pump over 10min through secure venous access.', 'interventionNames': ['Drug: Allopurinol']}
- {'label': 'Placebo', 'type': 'PLACEBO_COMPARATOR', 'description': 'mannitol, powder for injection (PFI), administered in two doses. First dose (20 mg/kg in 2ml/kg sterile water for injection) given as soon as intravenous access is established and no later than 30min postnatally and second dose (10mg/kg in 1ml/kg sterile water for injection) 12 hours thereafter. The second dose will only be administered to in infants on therapeutic hypothermia. Infants who recover quickly and do not qualify for and hence do not undergo hypothermia will not receive a second dose. Administration will be by continuous infusion using a syringe pump over 10min through secure venous access.', 'interventionNames': ['Drug: Mannitol']}

Interventions:
- {'type': 'DRUG', 'name': 'Allopurinol', 'description': 'Allopurinol, powder for injection (PFI), administered in two doses. First dose (20 mg/kg in 2ml/kg sterile water for injection) given as soon as intravenous access is established and no later than 30min postnatally and second dose (10mg/kg in 1ml/kg sterile water for injection) 12 hours thereafter. The second dose will only be administered to in infants on therapeutic hypothermia. Infants who recover quickly and do not qualify for and hence do not undergo hypothermia will not receive a second dose. Administration will be by continuous infusion using a syringe pump over 10min through secure venous access.', 'armGroupLabels': ['Allopurinol']}
- {'type': 'DRUG', 'name': 'Mannitol', 'description': 'Placebo (Mannitol, PFI, 20mg/kg in the same volume and at the same time intervals as the intervention group - (2nd dose 10mg/kg only if infant undergoes therapeutic hypothermia)).', 'armGroupLabels': ['Placebo']}

Primary Outcomes:
- {'measure': 'death versus severe neurodevelopmental impairment versus survival without severe neurodevelopmental impairment', 'description': 'Where severe neurodevelopmental impairment is defined as any of the following: cognitive or language delay defined as a cognitive-composite-score or a language-composite-score on the Bayley Scales of Infant and Toddler Development (3rd edition) \\< 85 and/or cerebral palsy (CP) according to SCPE criteria \\[SCPE Dev Med Child Neurol 2000\\]. In case of missing Bayley III test results, Bayley II or other developmental test results or PARCA-R parent questionnaire results may substitute for the Bayley III test result in a predefined hierarchical order.\n\nPrimary endpoint with three mutually exclusive responses (healthy, death, composite outcome for impairment) will be analyzed in the two treatment groups by a generalized logits model according to Bishop, Fienberg, Holland 1975 with SAS 9.4 procedure proc catmod.', 'timeFrame': 'at the age of 24 months'}

Please estimate the sample size based on the assumption: 
A two-sided X2-test with alpha = 0.05 and power of 80% was used. A drop-out rate of 10% for loss to follow-up and an additional 10% refusal rate after the initial dose were assumed.
Sample size, power and study duration
          The primary assessment for efficacy will compare the proportions of infants surviving without severe NDI versus those of infants who died or survived with severe NDI at the age of two years.
          Based on the above referenced (preliminary) clinical studies from the pre-therapeutic hypothermia era and clinical studies on hypothermic treatment, it is estimated that the combined incidence of death and severe NDI in the control group will be 37 and 27% in the allopurinol group. Therefore, we calculated with a two-sided X2-test (alphaâ=â0.05, power 80%) a sample size of 682 infants (341 per treatment group) in which the primary outcome should be ascertained. Assuming a drop-out rate of 10% for loss to follow-up, a total of 760 infants need to be enrolled. And assuming that 10% of the parents will refuse participation after the initial dose of the study drug, 846 infants have to be randomized (see Fig. 2).Fig. 2Anticipated Trial Flow
          We estimate a recruitment of about 35 patients per month in approximately 70 study centers (the recruitment of additional study sites is ongoing) and therefore recruitment will last 24âmonths.