Paracetamol Treatment of the Borderline Significant PDA

Patent Ductus Arteriosus Clinical Trial

Official title:

TIME TO RE-EVALUATE THE KINDER GENTLER APPROACH TO PATENT DUCTUS ARTERIOSUS (PDA) IN THE PRETERM NEONATE

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02819414
• Other study ID #: 0174-16-SZMC
• Status: Active, not recruiting
• Phase: Phase 2
• First received: June 28, 2016
• Last updated: July 2, 2016
• Start date: June 2016
• Est. completion date: January 2019

Study information

• Verified date: July 2016
• Source: Shaare Zedek Medical Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: Israel: Ministry of Health
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 80
• Est. completion date: January 2019
• Est. primary completion date: June 2018
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A to 6 Days

Eligibility

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

Study Design

Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Ductus Arteriosus, Patent
• Patent Ductus Arteriosus

Intervention

Drug:
• Paracetamol drops
15 mg/kg/dose x 4/day diluted 1:15 yielding dose of 2.25 ml/kg/dose to be given for three days

Other:
• Placebo
2.25 ml/kg/dose x 4/day of sterile water to be given for three days

Locations

Country	Name	City	State
Israel	Shaare Zedek Medical Center	Jerusalem

Sponsors (1)

Lead Sponsor	Collaborator
Shaare Zedek Medical Center

Country where clinical trial is conducted

Israel, 

References & Publications (2)

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. — View 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 p — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Composite outcome of death or severe morbidity chronic lung disease [CLD]	Chronic lung disease will be assessed by time on supplemental oxygen and assisted ventilation.	Day of life 3 until 40 weeks post-conception	No
Secondary	Subsequently diagnosed hs PDA	Will be assessed by subsequent need for medical or surgical intervention for closure of PDA	Completion of study intervention until 40 weeks post-conception	No
Secondary	Subsequent incidence of necrotizing enterocolitis (NEC) and/or retinopathy of prematurity (ROP)	Study infants will be followed clinically and any occurrence of NEC or ROP will be recorded with its level of significance (Bell staging for NEC and Stage of ROP)	Completion of study intervention until 40 weeks post-conception	No