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Echocardiographically Guided Versus Standard Ibuprofen Treatment for Patent Ductus Arteriosus

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Maria Carmen Bravo Laguna, Fundacion para la Investigacion Biomedica del Hospital Universitario la Paz
ClinicalTrials.gov Identifier:
NCT01593163
First received: May 3, 2012
Last updated: May 4, 2012
Last verified: May 2012

May 3, 2012
May 4, 2012
May 2009
March 2010   (final data collection date for primary outcome measure)
PDA re-opening rate [ Time Frame: Infants will be followed for the duration of hospital stay in the Newborn Unit, an expected average of 4-8 weeks ] [ Designated as safety issue: No ]
PDA re-opening after echocardiographically documented closure, which the attending physician deemed amenable to additional treatment. Infants with ventilator weaning difficulty, protracted metabolic acidosis or persistent hemodynamic instability were included in this category.
Same as current
Complete list of historical versions of study NCT01593163 on ClinicalTrials.gov Archive Site
  • treatment failure [ Time Frame: Infants will be followed for the duration of hospital stay in the Newborn Unit, an expected average of 4-8 weeks ] [ Designated as safety issue: No ]
    PDA ≥ 1.5 mm 24 hours after a complete ibuprofen course
  • need for surgical ligation [ Time Frame: Infants will be followed for the duration of hospital stay in the Newborn Unit, an expected average of 4-8 weeks ] [ Designated as safety issue: No ]
    need for surgical ligation
  • need for additional ibuprofen doses [ Time Frame: Infants will be followed for the duration of hospital stay in the Newborn Unit, an expected average of 4-8 weeks ] [ Designated as safety issue: No ]
    need for additional ibuprofen doses after treatment was completed
  • urine output [ Time Frame: before the first ibuprofen dose was administered (between 12-72 hours of life) until 24 hours after the last dose of ibuprofen was administered (between 36-168 h of life) ] [ Designated as safety issue: Yes ]
    urine output
  • serum creatinine [ Time Frame: before the first ibuprofen dose was administered (between 12-72 hours of life) until 24 hours after the last dose of ibuprofen was administered (between 36-168 h of life) ] [ Designated as safety issue: Yes ]
    serum creatinine
  • mortality [ Time Frame: Infants will be followed for the duration of hospital stay in the Newborn Unit, an expected average of 4-8 weeks ] [ Designated as safety issue: Yes ]
    mortality
  • bronchopulmonary dysplasia [ Time Frame: Infants will be followed for the duration of hospital stay in the Newborn Unit, an expected average of 4-8 weeks ] [ Designated as safety issue: Yes ]
    bronchopulmonary dysplasia (O2 need at 36 postmenstrual weeks)
  • necrotising enterocolitis [ Time Frame: Infants will be followed for the duration of hospital stay in the Newborn Unit, an expected average of 4-8 weeks ] [ Designated as safety issue: Yes ]
    necrotising enterocolitis
  • intraventricular hemorrhage [ Time Frame: Infants will be followed for the duration of hospital stay in the Newborn Unit, an expected average of 4-8 weeks ] [ Designated as safety issue: Yes ]
    intraventricular hemorrhage
  • White matter damage [ Time Frame: Infants will be followed for the duration of hospital stay in the Newborn Unit, an expected average of 4-8 weeks ] [ Designated as safety issue: Yes ]
    White matter damage
  • Laser therapy for retinopathy [ Time Frame: Infants will be followed for the duration of hospital stay in the Newborn Unit, an expected average of 4-8 weeks ] [ Designated as safety issue: Yes ]
    Laser therapy for retinopathy
  • peak systolic velocity [ Time Frame: before each ibuprofen dose should be administered (3 days) and 24 hours after the last dose of ibuprofen was administered ] [ Designated as safety issue: No ]
    peak systolic velocity measured by means of cerebral Doppler ultrasonography in the anterior and middle cerebral arteries
  • end-diastolic velocity [ Time Frame: before each ibuprofen dose should be administered (3 days) and 24 hours after the last dose of ibuprofen was administered ] [ Designated as safety issue: No ]
    end-diastolic velocity measured by means of cerebral Doppler ultrasonography in the anterior and middle cerebral arteries
  • resistance index [ Time Frame: before each ibuprofen dose should be administered (3 days) and 24 hours after the last dose of ibuprofen was administered ] [ Designated as safety issue: No ]
    resistance index measured by means of cerebral Doppler ultrasonography in the anterior and middle cerebral arteries
  • pulsatility index [ Time Frame: before each ibuprofen dose should be administered (3 days) and 24 hours after the last dose of ibuprofen was administered ] [ Designated as safety issue: No ]
    pulsatility index measured by means of cerebral Doppler ultrasonography in the anterior and middle cerebral arteries
Same as current
Not Provided
Not Provided
 
Echocardiographically Guided Versus Standard Ibuprofen Treatment for Patent Ductus Arteriosus
Randomised Controlled Clinical Trial of Echocardiographically Guided Versus Standard Ibuprofen Treatment for Patent Ductus Arteriosus: a Pilot Study

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.

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.

Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Patent Ductus Arteriosus
  • Drug: 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.
    Other Name: Echocardiographically guided ibuprofen treatment
  • 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.
    Other Name: Standard ibuprofen treatment
  • Experimental: 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: Drug: Ibuprofen EchoG
  • 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.
    Intervention: Drug: Standard ibuprofen treatment
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. Epub 2009 Jul 29.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
49
March 2010
March 2010   (final data collection date for primary outcome measure)

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
Both
up to 1 Month
No
Contact information is only displayed when the study is recruiting subjects
Spain
 
NCT01593163
IbuEchoG
Yes
Maria Carmen Bravo Laguna, Fundacion para la Investigacion Biomedica del Hospital Universitario la Paz
Fundacion para la Investigacion Biomedica del Hospital Universitario la Paz
Not Provided
Principal Investigator: María Carmen Bravo, PhD MD Department of Neonatology, La Paz University Hospital
Study Chair: Fernando Cabañas, PhDMD Department of Neonatology, La Paz University Hospital
Study Chair: Joan Riera, Bio-Engineer Department of Neonatology, La Paz University Hospital
Study Chair: Elia Pérez-Fernández Division of Statistics, La Paz University Hospital. Madrid, Spain.
Study Chair: José Quero, PhDMD Department of Neonatology, La Paz University Hospital. Madrid, Spain.
Study Chair: Jesús Pérez-Rodríguez, PhDMD Department of Neonatology, La Paz University Hospital. Madrid, Spain.
Study Director: Adelina Pellicer, PhDMD Department of Neonatology, La Paz University Hospital. Madrid, Spain.
Fundacion para la Investigacion Biomedica del Hospital Universitario la Paz
May 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP