Echocardiographically Guided Versus Standard Ibuprofen Treatment for Patent Ductus Arteriosus

Patent Ductus Arteriosus Clinical Trial

Official title:

Randomised Controlled Clinical Trial of Echocardiographically Guided Versus Standard Ibuprofen Treatment for Patent Ductus Arteriosus: a Pilot Study

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01593163
• Other study ID #: IbuEchoG
• Status: Completed
• Phase: Phase 3
• First received: May 3, 2012
• Last updated: May 4, 2012
• Start date: May 2009
• Est. completion date: March 2010

Study information

• Verified date: May 2012
• Source: Fundacion para la Investigacion Biomedica del Hospital Universitario la Paz
• Contact: n/a
• Is FDA regulated: No
• Health authority: Spain: Comité Ético de Investigación Clínica
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 49
• Est. completion date: March 2010
• Est. primary completion date: March 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A to 1 Month

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Ductus Arteriosus, Patent
• Patent Ductus Arteriosus

Intervention

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.
• 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.

Locations

Country	Name	City	State
Spain	Department of Neonatology, La Paz University Hospital	Madrid

Sponsors (1)

Lead Sponsor	Collaborator
Fundacion para la Investigacion Biomedica del Hospital Universitario la Paz

Country where clinical trial is conducted

Spain, 

References & Publications (1)

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	PDA re-opening rate	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.	Infants will be followed for the duration of hospital stay in the Newborn Unit, an expected average of 4-8 weeks	No
Secondary	treatment failure	PDA = 1.5 mm 24 hours after a complete ibuprofen course	Infants will be followed for the duration of hospital stay in the Newborn Unit, an expected average of 4-8 weeks	No
Secondary	need for surgical ligation	need for surgical ligation	Infants will be followed for the duration of hospital stay in the Newborn Unit, an expected average of 4-8 weeks	No
Secondary	need for additional ibuprofen doses	need for additional ibuprofen doses after treatment was completed	Infants will be followed for the duration of hospital stay in the Newborn Unit, an expected average of 4-8 weeks	No
Secondary	urine output	urine output	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)	Yes
Secondary	serum creatinine	serum creatinine	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)	Yes
Secondary	mortality	mortality	Infants will be followed for the duration of hospital stay in the Newborn Unit, an expected average of 4-8 weeks	Yes
Secondary	bronchopulmonary dysplasia	bronchopulmonary dysplasia (O2 need at 36 postmenstrual weeks)	Infants will be followed for the duration of hospital stay in the Newborn Unit, an expected average of 4-8 weeks	Yes
Secondary	necrotising enterocolitis	necrotising enterocolitis	Infants will be followed for the duration of hospital stay in the Newborn Unit, an expected average of 4-8 weeks	Yes
Secondary	intraventricular hemorrhage	intraventricular hemorrhage	Infants will be followed for the duration of hospital stay in the Newborn Unit, an expected average of 4-8 weeks	Yes
Secondary	White matter damage	White matter damage	Infants will be followed for the duration of hospital stay in the Newborn Unit, an expected average of 4-8 weeks	Yes
Secondary	Laser therapy for retinopathy	Laser therapy for retinopathy	Infants will be followed for the duration of hospital stay in the Newborn Unit, an expected average of 4-8 weeks	Yes
Secondary	peak systolic velocity	peak systolic velocity measured by means of cerebral Doppler ultrasonography in the anterior and middle cerebral arteries	before each ibuprofen dose should be administered (3 days) and 24 hours after the last dose of ibuprofen was administered	No
Secondary	end-diastolic velocity	end-diastolic velocity measured by means of cerebral Doppler ultrasonography in the anterior and middle cerebral arteries	before each ibuprofen dose should be administered (3 days) and 24 hours after the last dose of ibuprofen was administered	No
Secondary	resistance index	resistance index measured by means of cerebral Doppler ultrasonography in the anterior and middle cerebral arteries	before each ibuprofen dose should be administered (3 days) and 24 hours after the last dose of ibuprofen was administered	No
Secondary	pulsatility index	pulsatility index measured by means of cerebral Doppler ultrasonography in the anterior and middle cerebral arteries	before each ibuprofen dose should be administered (3 days) and 24 hours after the last dose of ibuprofen was administered	No