Closure of Patent Ductus Arteriosus With Indomethacin or Ibuprofen in Extreme Low Birth Weight Infants

Pharmacological Closure of Patent Ductus Arteriosus in Extreme Low Birth Weight Infants. A Comparison of Efficacy, Side Effects and Outcomes Between Indomethacin and Ibuprofen

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.

Study Overview

• Status: Completed
• Conditions: Patent Ductus Arteriosus
• Intervention / Treatment: Drug: 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.

• Study Type: Interventional
• Enrollment (Actual): 110
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Illinois
    • Chicago, Illinois, United States, 60612
      • John H. Stroger, Jr. Hospital of Cook County

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 6 months (CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Ibuprofen; Infant who was assigned to ibuprofen, an initial dose of 10 mg/kg, followed by 5 mg/kg at 24 and 48 hours respectively as a course was given.	Drug: Ibuprofen; To compare the efficacy, the side effects and the renal prostaglandin (PG) excretion between indomethacin and ibuprofen in extremely low birth weight (ELBW) infants.; Other Names: 2-[4-(2-methylpropyl)phenyl]propanoic acid

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of infants with ductus closure	To compare the number of infants with ductus closure treated with indomethacin and ibuprofen in extremely low birth weight infants.	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Urine output	To compare the urine output between indomethacin and ibuprofen treatment in extremely low birth weight infants.	1 month

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Serum creatinine	To compare serum creatinine between indomethacin and ibuprofen treatment in extremely low birth weight infants.	1 month

Collaborators and Investigators

• Sponsor: Taipei Medical University Hospital
• Collaborators: China Medical University Hospital; John H. Stroger Hospital
• Investigators: Principal Investigator: Tsu-Fu Yeh, MD, PhD, Taipei Medical University

Publications and helpful links

General Publications

• 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.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start: February 1, 2007
• Primary Completion (ACTUAL): February 1, 2012
• Study Completion (ACTUAL): February 1, 2012

Study Registration Dates

• First Submitted: December 16, 2012
• First Submitted That Met QC Criteria: December 27, 2012
• First Posted (ESTIMATE): January 1, 2013

Study Record Updates

• Last Update Posted (ESTIMATE): January 3, 2013
• Last Update Submitted That Met QC Criteria: January 1, 2013
• Last Verified: December 1, 2012

More Information

Terms related to this study

• Keywords: Bronchopulmonary dysplasia; prostaglandin; patent ductus arteriosus; Respiratory distress syndrome
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Congenital Abnormalities; Body Weight; Heart Defects, Congenital; Cardiovascular Abnormalities; Birth Weight; Ductus Arteriosus, Patent; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Cyclooxygenase Inhibitors; Ibuprofen
• Other Study ID Numbers: PDA Ind Ibu ELBW