Please select the eligibility criteria that correspond to the clinical trial below.
Title: Randomized Pilot Study Comparing Oral Ibuprofen With Intravenous Ibuprofen in Very Low Birth Weight Infants With Patent Ductus Arteriosus
Brief Summary: it is a prospective randomized simple-blinded pilot trial with the principal aim to compare efficacy and tolerance between oral ibuprofen and intravenous ibuprofen in early curative closure of PDA in very low birth weight infants. The likelihood of ductal closure with only one or two doses of treatment is a secondary objective.


Options:
A: Inclusion Criteria:

* PDA diameter \> 1.5 mm and ductal (predominantly) left-to-right shunt
* Signed informed consent obtained from parent(s) or representative(s)
* Gestational age \< 28 completed weeks

Exclusion Criteria:

* Contraindication for administration of cyclooxygenase-inhibitors (COXi)
* Persistent pulmonary hypertension (ductal right-to-left shunt ≧33% of cardiac cycle)
* Congenital heart defect, other than PDA and/or patent foramen ovale (PFO)
* Life-threatening congenital defects
* Chromosomal abnormalities and/or congenital anomalies associated with abnormal neurodevelopmental outcome
* Use of COXi prior to randomization
B: Inclusion Criteria:

* a gestational age \< 32 weeks
* a birth weight \< 1500g
* a postnatal age between 48 and 96 hours, a respiratory distress requiring more than 25 % of oxygen supplementation
* an echocardiographic evidence of left to right significant shunting PDA

Exclusion Criteria:

* a right-to-left shunting
* major congenital anomalies
* IVH grade 3-4
* a tendency to bleed (defined by the presence of blood in the endotracheal aspirate, gastric aspirate, stools or urines and / or oozing from puncture sites)
* a serum creatinine level \>140µmol/l, a serum urea nitrogen \> 14 µmol/l and a platelet count \< 60000/mm3.
C: Inclusion Criteria:

1. Male or female preterm infants with no limitation of race.
2. Gestational age 25(+0) - 31(+6) weeks.
3. Age 24-72 hours.
4. Echocardiographic evidence of hemodynamically significant patent ductus arteriosus at the first 24-72 hours of life.

   The diagnosis of hemodynamically significant PDA requiring treatment will be made by echocardiographic demonstration of a ductal left-to-right shunt, with a left atrium-to-aortic root ratio \>1.3 or a ductal size \>1.5 mm and excluding the cases in which the closing flow pattern suggests a restrictive PDA.
5. Willingness of the parents/legally authorized representative/child to sign the Consent Informed Form.

Exclusion Criteria:

1. Outborn patients.
2. Major congenital anomalies, including but not limited to congenital heart defects, Down syndrome newborn and/or new born suffering from congenital anomalies diagnosed during the fetal period.
3. Known positive HIV and/or known positive Hepatitis C Virus newborn's mother.
4. Life threatening infection, complicated or not by multiple organ dysfunction and failure syndrome.
5. Fetal hydrops.
6. Pulmonary hypertension diagnosed in the first 24-48 hours of life by means of heart ultrasound when the presence of a right-to-left shunt through the foramen ovale or ductus arteriosus is demonstrated, or when the estimated pulmonary pressure, in terms of the tricuspid regurgitation jet, is greater than two-thirds of the systemic arterial pressure.
7. Grade 3 or 4 intraventricular haemorrhage (IVH).
8. Urine output \<1 ml/kg of body weight/h during a 24 h collection period or urine output \<0.5 ml/kg of body weight/h in case it is measured at 24 hours of life of newborn.
9. Serum creatinine concentration \> 1.5 mg/dl (132 μmol/l).
10. Platelet count \< 50,000/mm3.
11. Major bleeding, as revealed by hematuria, or blood in the endotracheal aspirate, gastric aspirate, or stools, or consistent oozing of blood from puncture sites.
12. Severe liver failure, defined as elevated liver enzymes (ALT/Glutamate-Pyruvate Transaminase and Aspartate aminotransferase/GOT) \> 2 times the upper boundary of the normal range. For this kind of population the following normal ranges will be considered \[Rosenthal, 1997\]:

    * ALT/Glutamate-pyruvate transaminase: 6-50 U/L
    * Aspartate aminotransferase/GOT: 35-140 U/L
13. Medical need of administering other Nonsteroidal Antiinflammatory Drug (NSAID) different from ibuprofen.
14. Participation to another trial involving any investigational drug.
D: Inclusion Criteria:

* Gestational less than 28 weeks
* Postnatal age less than 12 hours

Answer: B