Clinical trial NCT01758913: Closure of Patent Ductus Arteriosus With Indomethacin or Ibuprofen in Extreme Low Birth Weight Infants
Official title: Pharmacological Closure of Patent Ductus Arteriosus in Extreme Low Birth Weight Infants. A Comparison of Efficacy, Side Effects and Outcomes Between Indomethacin and Ibuprofen
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Patent Ductus Arteriosus
Keywords: Bronchopulmonary dysplasia
patent ductus arteriosus
prostaglandin
Respiratory distress syndrome
Lead sponsor: Taipei Medical University Hospital
Sponsor class: OTHER
Collaborators: name: Cook County Health
name: China Medical University Hospital
First posted: 2013-01-01
Enrollment: 110
Sex: ALL
Maximum age (years): 6
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Pharmacological closure of ductus arteriosus with prostaglandin (PG) inhibitors has been used for years. Previous studies indicated that ibuprofen has similar effect on ductal closure as indomethacin but has less adverse effects on renal function, cerebral blood flow and mesenteric blood flow.1-7 There are, however, very few studies being done specifically on extremely low birth weight (ELBW) infant \< 1000 g. This group of infants has immature kidney and often has poor response to PG inhibitors and has high mortality and morbidity. We hypothesized that, in ELBW infants, the ductal and renal response to PG inhibitors may be different between indomethacin and ibuprofen.

Detailed description: The aims of this study are to compare the efficacy, the side effects and the renal prostaglandin (PG) excretion between indomethacin and ibuprofen in extremely low birth weight (ELBW) infants. We enrolled one hundred and ten ELBW infants who had clinically significant and echo-evidence patent ductus arteriosus were assigned into 2 groups, 56 received indomethacin (0.2 mg/kg, 0.1 mg/kg and 0.1 mg/kg in 24 hours interval) and 54 received ibuprofen (10 mg/kg, 5mg/kg and 5 mg/kg in 24 hours interval). Serum electrolytes, creatinine, renal function (urine output, glomerular filtration rate (GFR), fractional excretion of sodium and potassium, osmolar clearance and free water clearance), urinary PG excretion, pulmonary outcome and mortality were all evaluated.

Eligibility criteria: Inclusion Criteria:

* The selection criteria were: (1) preterm infants with birth weight \<1000 g; 2) radiographic diagnosis of respiratory distress syndrome (RDS); (3) requirement of mechanical ventilation and (4) echocardiographic and clinical evidence of significant patent ductus arteriosus (PDA).

Exclusion Criteria:

* Exclusion criteria included: (1) evidence of infection or sepsis; 2) lethal congenital anomalies; (3) oliguria (\< 1 ml/kg/h) and/or serum creatinine \> 2.0 mg/dl and (4) low platelet count (\< 50,000/mm3) or bleeding tendency.

Primary outcomes:
measure: Number of infants with ductus closure
timeFrame: 6 months
Secondary outcomes:
measure: Urine output
timeFrame: 1 month
Other outcomes:
measure: Serum creatinine
timeFrame: 1 month
Locations:
city: Chicago
country: United States
facility: John H. Stroger, Jr. Hospital of Cook County
state: Illinois
Study officials:
affiliation: Taipei Medical University
name: Tsu-Fu Yeh, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Yeh TF, Achanti B, Patel H, Pildes RS. Indomethacin therapy in premature infants with patent ductus arteriosus--determination of therapeutic plasma levels. Dev Pharmacol Ther. 1989;12(4):169-78.
citation: Yeh TF, Raval D, Luken J, Thalji A, Lilien L, Pildes RS. Clinical evaluation of premature infants with patent ductus arteriosus: a scoring system with echocardiogram, acid-base, and blood gas correlations. Crit Care Med. 1981 Sep;9(9):655-7. doi: 10.1097/00003246-198109000-00009.
citation: Yeh TF, Luken J, Raval D, Thalji A, Carr I, Pildes RS. Indomethacin treatment in small versus large premature infants with ductus arteriosus. Comparison of plasma indomethacin concentration and clinical response. Br Heart J. 1983 Jul;50(1):27-30. doi: 10.1136/hrt.50.1.27.