Safety and Efficacy Study of Ibuprofen l-Lysine Solution in Premature Infants for Treatment of PDA

Condition(s) targeted: Patent Ductus Arteriosus

Intervention: ibuprofen l-lysine iv solution (NeoProfen (R) ) (Drug)

Phase: Phase 3

Status: Completed

Sponsored by: Farmacon

Official(s) and/or principal investigator(s):
Jacob V Aranda, MD, PhD, Principal Investigator, Affiliation: Unaffiliated

The purpose of this study is to determine the safety and effectiveness of ibuprofen l-lysine iv in premature infants in the early treatment of Patent Ductus Arteriosus.

Official title: Randomized, Double-Blind Study of Ibuprofen L-Lysine Intravenous Solution in Premature Infants for the Early Treatment of Patent Ductus Arteriosus

Study design: Treatment, Randomized, Double-Blind, Placebo Control, Parallel Assignment, Efficacy Study

Primary outcome: Primary Outcome Measures (Efficacy)

Secondary outcome:

Gastrointestinal function

Renal function

Hematology

Liver enzyme tests

Serum bilirubin

Respiratory function

Intraventricular hemorrhage

Pulmonary hemorrhage

Pulmonary hypertension

Exploratory outcomes:

Ibuprofen concentrations

Prostanoid concentrations

CYP2C9 Genotyping

Follow-up Outcomes

Retinopathy of Prematurity

Bronchopulmonary dysplsia

Periventricular leukomalacia

Detailed description: The ductus arteriosus remains patent in about 40% to 80% of very low birth weight infants. Early treatment by intravenous ibuprofen L-lysine (IV ibuprofen) has been suggested in preliminary studies to close the ductus and shorten hospital stay. This study aims to determine the effect of early treatment with IV ibuprofen given to the very low birth weight infant with a non-symptomatic patent ductus arteriosus (PDA) at less than 72 hours of life to accelerate and maintain ductal closure, thereby reducing the need for rescue therapy.

Minimum age: 28 Weeks. Maximum age: 34 Weeks. Gender(s): Both.

Criteria:

Inclusion Criteria:

- Premature newborn infant of either gender with a birth weight of 500 to 1000 grams,

appropriate for gestational age;

- Non-symptomatic PDA with evidence of ductal shunting documented by an echocardiogram

(ECHO);

- Less than 72 hours of age at the time of randomization;

- If infant is one of a multiple birth, he/she is one of the two (2) oldest infants who

meet the eligibility criteria;

- Consent form signed by parent.

Exclusion Criteria:

- Either major congenital malformations and/or chromosomal anomalies;

- Proven, severe congenital bacterial infection;

- Maternal antenatal nonsteroidal anti-inflammatory drug (NSAID) exposure < 72 hours

prior to delivery;

- Treatment with pharmacological replacement steroid therapy at anytime since birth;

- Unremitting shock requiring very high doses of vasopressors (i. e. inability to

maintain mean arterial blood pressure appropriate for gestational age ± 2 SD using volume and maximal vasopressor therapy as defined by the individual institution);

- Renal failure or oliguria defined as urine flow rate < 0. 5 mL/kg/hr in the 8 hours

prior to randomization (Anuria is acceptable if infant is in first 24 hours of life);

- Platelet count < 75,000/mm 3;

- Clinical bleeding tendency (i. e. oozing from puncture sites);

- Expected survival less than 48 hours in the opinion of the attending neonatologist;

- Participation in other clinical intervention trials. Exceptions may be made if

approved by Medical Director or designee, RPD Pharmaceutical Department;

- Symptomatic PDA as documented by 3 of the following 5 criteria

- Bounding pulse

- Hyperdynamic precordium

- Pulmonary edema

- Increased cardiac silhouette

- Systolic murmur Or, in view of the neonatologist is deemed to have a hemodynamically

significant ductus.

- Exposure to NSAIDs at any time since birth.

Starting date: December 2002
Ending date: August 2005
Last updated: February 23, 2007