Clinical trial NCT00440804: Safety and Efficacy Study of Ibuprofen l-Lysine Solution in Premature Infants for Treatment of PDA
Official title: Randomized, Double-Blind Study of Ibuprofen L-Lysine Intravenous Solution in Premature Infants for the Early Treatment of Patent Ductus Arteriosus
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Patent Ductus Arteriosus
Keywords: patent ductus arterious
Lead sponsor: Farmacon
Sponsor class: INDUSTRY
First posted: 2007-02-27
Sex: ALL
Minimum age (years): 28
Maximum age (years): 34
Standard ages: CHILD
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility 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.

Primary outcomes:
measure: Primary Outcome Measures (Efficacy)
Secondary outcomes:
measure: Gastrointestinal function
measure: Renal function
measure: Hematology
measure: Liver enzyme tests
measure: Serum bilirubin
measure: Respiratory function
measure: Intraventricular hemorrhage
measure: Pulmonary hemorrhage
measure: Pulmonary hypertension
measure: Exploratory outcomes:
measure: Ibuprofen concentrations
measure: Prostanoid concentrations
measure: CYP2C9 Genotyping
measure: Follow-up Outcomes
measure: Retinopathy of Prematurity
measure: Bronchopulmonary dysplsia
measure: Periventricular leukomalacia
Other outcomes:
Locations:
Study officials:
name: Jacob V Aranda, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: