Clinical trial NCT02819414: Paracetamol Treatment of the Borderline Significant PDA
Official title: TIME TO RE-EVALUATE THE KINDER GENTLER APPROACH TO PATENT DUCTUS ARTERIOSUS (PDA) IN THE PRETERM NEONATE
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Patent Ductus Arteriosus
Lead sponsor: Shaare Zedek Medical Center
Sponsor class: OTHER
First posted: 2016-06-30
Enrollment: 80
Sex: ALL
Minimum age (years): 3
Maximum age (years): 6
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The therapeutic approach to the patent ductus arteriosus (PDA) in the premature neonate remains controversial. Currently it is generally accepted to treat only hemodynamically significant PDAs. The current investigation aims to study the effect of treatment on PDAs of borderline significance via a prospective, randomized controlled trial of paracetamol in this group.

Detailed description: In the neonatal intensive care unit of the Shaare Zedek Medical Center, preterm babies \<30 wks. GA, are studied echocardiographically on day of life 3-4. Pending parental informed consent, those diagnosed with a PDA of borderline significance will be randomized to receive either paracetamol or placebo for three days, followed by a repeat echocardiogram. If the PDA remains of borderline significance, the treatment will be continued for an additional 4 days (1 week total). Paracetamol levels and liver functions will be assessed after the third day. Babies will be followed until discharge for subsequent PDA pathology; respiratory distress and chronic lung disease \[CLD\]; necrotizing enterocolitis \[NEC\]; retinopathy of prematurity \[ROP\].

The investigators' primary goal is to demonstrate a decrease in the composite outcome of death or severe morbidity chronic lung disease \[CLD\], as shown by decreased time on supplemental oxygen and assisted ventilation.

Secondary goals:

* To demonstrate a decrease in subsequently diagnosed hs PDA, including

  * Decrease in the need for subsequent therapy for PDA closure
  * Decrease in surgical PDA ligations
* To demonstrate a decrease in necrotizing enterocolitis (NEC) and/or ROP with treatment.
* To demonstrate no adverse effect on blood flow in anterior cerebral, superior mesenteric and renal arteries.

Eligibility criteria: Inclusion Criteria:

* Preterm neonates \< 30 weeks' gestational age PDA of borderline significance

Exclusion Criteria:

* Infants not deemed likely to survive more than one week Infants with congenital heart malformations Infants with pulmonary hypertension and right to left ductal shunting

Primary outcomes:
measure: Composite outcome of death or severe morbidity chronic lung disease [CLD]
timeFrame: Day of life 3 until 40 weeks post-conception
Secondary outcomes:
measure: Subsequently diagnosed hs PDA
timeFrame: Completion of study intervention until 40 weeks post-conception
measure: Subsequent incidence of necrotizing enterocolitis (NEC) and/or retinopathy of prematurity (ROP)
timeFrame: Completion of study intervention until 40 weeks post-conception
Other outcomes:
Locations:
city: Jerusalem
country: Israel
facility: Shaare Zedek Medical Center
Study officials:
affiliation: Shaare Zedek Medical Center
name: Cathy Hammerman, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Terrin G, Conte F, Oncel MY, Scipione A, McNamara PJ, Simons S, Sinha R, Erdeve O, Tekgunduz KS, Dogan M, Kessel I, Hammerman C, Nadir E, Yurttutan S, Jasani B, Alan S, Manguso F, De Curtis M. Paracetamol for the treatment of patent ductus arteriosus in preterm neonates: a systematic review and meta-analysis. Arch Dis Child Fetal Neonatal Ed. 2016 Mar;101(2):F127-36. doi: 10.1136/archdischild-2014-307312. Epub 2015 Aug 17.
citation: Hammerman C, Bin-Nun A, Markovitch E, Schimmel MS, Kaplan M, Fink D. Ductal closure with paracetamol: a surprising new approach to patent ductus arteriosus treatment. Pediatrics. 2011 Dec;128(6):e1618-21. doi: 10.1542/peds.2011-0359. Epub 2011 Nov 7.