Echocardiographically Guided Versus Standard Ibuprofen Treatment for Patent Ductus Arteriosus

NCT ID: NCT01593163

Last Updated: 2012-05-08

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 49 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-05-31
• Study Completion Date: 2010-03-31

Brief Summary

Patent ductus arteriosus (PDA) is a very common condition in immature newborn babies and it has been associated to morbidity and mortality. Ibuprofen is the drug of choice for PDA treatment according to the last version of the Cochrane review. Nowadays the best dose regimen for ibuprofen remains uncertain. The investigators aim to perform a randomized controlled clinical trial to assess whether echocardiographically guided PDA ibuprofen treatment versus standard treatment could reduce the number of doses of ibuprofen without increasing the reopening rate and reducing the side effects associated to this medication.

Detailed Description

Patent ductus arteriosus (PDA) is presented in 55 to 70% of the preterm infants with a gestational age lower than 30 weeks or a birth weight lower than 1000 grams. PDA has being associated to mortality or morbidity such as ischemic or hemorrhagic cerebral events, necrotising enterocolitis, renal disfunction or poor pulmonary outcome; however, it is not clear whether these are a consequence of the PDA presence, the treatment implemented for closing it, or the immaturity of these population. PDA standard treatment (ST) consists on three doses of indomethacin or ibuprofen (10-5-5mg/kg) given 24 hours apart, being the surgical closure a second line therapeutic option. In spite of ibuprofen has been pointed as the drug of choice for PDA treatment by the last version of the Cochrane review, side effects have been associated to both medication. Standard ibuprofen treatment is based on a clinical trial where the three-dose protocol seemed to be more effective than one-dose scheme for PDA closure; however, the sample size was not powered to find differences statistically significant, so nowadays the best dose regimen for ibuprofen remains uncertain. Functional echocardiographic assessment is spreading to all over the world. In this scenario, it has been proposed its implementation to guide PDA treatment in order to individualize the number of doses of indomethacin administered as a function of patient's response, limiting the doses and side effects in those where PDA presented an early constriction. The investigators hypothesized whether echocardiographically guided PDA ibuprofen treatment could reduce the number of doses of ibuprofen without increasing the reopening rate and reducing the side effects associated to this medication.

Conditions

Patent Ductus Arteriosus

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

EchoG

Infants in the experimental group (echoG treatment) received additional doses of ibuprofen only if PDA was still ≥ 1.5 mm at the time of the corresponding ibuprofen dose.

Group Type: EXPERIMENTAL

Ibuprofen EchoG

Intervention Type: DRUG

Infants in the experimental group (echoG treatment) received additional doses of ibuprofen only if PDA was still ≥ 1.5 mm at the time of the corresponding ibuprofen dose.

ST (standard treatment)

Infants received 3 doses of ibuprofen at 24-hour intervals, independently of ductal size, as long as additional doses were not contraindicated.

Group Type: OTHER

Standard ibuprofen treatment

Intervention Type: DRUG

Infants received 3 doses of ibuprofen at 24-hour intervals, independently of ductal size, as long as additional doses were not contraindicated.

Interventions

Ibuprofen EchoG

Infants in the experimental group (echoG treatment) received additional doses of ibuprofen only if PDA was still ≥ 1.5 mm at the time of the corresponding ibuprofen dose.

Intervention Type: DRUG

Standard ibuprofen treatment

Infants received 3 doses of ibuprofen at 24-hour intervals, independently of ductal size, as long as additional doses were not contraindicated.

Intervention Type: DRUG

Other Intervention Names

Echocardiographically guided ibuprofen treatment

Eligibility Criteria

Inclusion Criteria

• Preterm infants with a gestational age lower than 37 weeks of gestational age
• PDA ≥ 1.5 mm
• No contraindication to receive ibuprofen
• Informed consent signed.

Exclusion Criteria

• Life-threatening congenital defects
• Congenital heart disease
• Contraindication for ibuprofen administration such as oligoanuria < 1cc/kg/h or recent severe intraventricular bleeding (IVH grade III) or creatinine serum level > 1.5 mg/dl or potential intestinal ischemia.
• Informed consent refused

• Maximum Eligible Age: 1 Month
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Fundacion para la Investigacion Biomedica del Hospital Universitario la Paz

OTHER

Sponsor Role: lead

Responsible Party

Maria Carmen Bravo Laguna

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

María Carmen Bravo, PhD MD

Role: PRINCIPAL_INVESTIGATOR

Department of Neonatology, La Paz University Hospital

Fernando Cabañas, PhDMD

Role: STUDY_CHAIR

Department of Neonatology, La Paz University Hospital

Joan Riera, Bio-Engineer

Role: STUDY_CHAIR

Department of Neonatology, La Paz University Hospital

Elia Pérez-Fernández

Role: STUDY_CHAIR

Division of Statistics, La Paz University Hospital. Madrid, Spain.

José Quero, PhDMD

Role: STUDY_CHAIR

Department of Neonatology, La Paz University Hospital. Madrid, Spain.

Jesús Pérez-Rodríguez, PhDMD

Role: STUDY_CHAIR

Department of Neonatology, La Paz University Hospital. Madrid, Spain.

Adelina Pellicer, PhDMD

Role: STUDY_DIRECTOR

Department of Neonatology, La Paz University Hospital. Madrid, Spain.

Locations

Department of Neonatology, La Paz University Hospital

Madrid, Madrid, Spain

Countries

Spain

References

Carmo KB, Evans N, Paradisis M. Duration of indomethacin treatment of the preterm patent ductus arteriosus as directed by echocardiography. J Pediatr. 2009 Dec;155(6):819-822.e1. doi: 10.1016/j.jpeds.2009.06.013. Epub 2009 Jul 29.

Reference Type: BACKGROUND

PMID: 19643435 (View on PubMed)

Other Identifiers

IbuEchoG

Identifier Type: -

Identifier Source: org_study_id