Comparison of Infusion Paracetamol Protocols in PDA

Comparison of The Effect of Continuous and Standard Intermittent Boluses Paracetamol Infusion on Patent Ductus Arteriosus

The aim of this study was to evaluate the effect of paracetamol on patent ductus arteriosus (PDA) closure and clinical outcomes in preterm infants when used as standard intermittent bolus and continuous intravenous (IV) infusion. Preterm neonates with birth weight (BW) ≤1500 g and gestational age (GA) ≤32 weeks were included in this study. During the study period, IV paracetamol therapy was given to all infants with hemodynamically significant patent ductus arteriosus (hsPDA). The patients were divided into the standard IV intermittent bolus infusion group and the continuous IV infusion group.

Study Overview

• Status: Completed
• Conditions: Patent Ductus Arteriosus in Preterm Infants
• Intervention / Treatment: Drug: Paracetamol Infusion

Detailed Description

Demographic and clinical features Perinatal variables were recorded for all infants, including GA, BW, sex, APGAR scores (at 1 and 5 minutes), prenatal steroids, pre- and post-treatment alanine aminotransferase (ALT)/aspartate aminotransferase (AST), second and third courses of paracetamol, PDA ligation, clinical variables including respiratory distress syndrome (RDS), IVH (grade ≥3), NEC (grade≥2), moderate or severe BPD, ROP requiring laser therapy, early-onset neonatal sepsis (EOS), late-onset sepsis (LOS), duration of non-invasive ventilation (NIV), mechanical ventilation (MV) and oxygen (O2) supplementation, day of full enteral feeding achievement, length of hospital stay, and mortality.

Sepsis with onset at ≤72 hours was defined as EOS and at >72 hours as LOS in infants hospitalized in the NICU. RDS was defined as the need for surfactant administration [5]. IVH was diagnosed by cranial ultrasound in the first 7 days of life (intraparenchymal hemorrhage + IVH, large IVH). NEC diagnosis and staging were implemented by using Bell's criteria. Neonates that received positive pressure or ≥30% oxygen without pressure after a postmenstrual age of 36 weeks were diagnosed as having moderate or severe BPD [8]. ROP screening was done by ophthalmologists according to the International Classification of Retinopathy of Prematurity Revisited [9].

Hemodynamically Significant Patent Ductus Arteriosus All neonates underwent Doppler echocardiography (ECHO) at postnatal 72 hours. Diagnosis of hsPDA was based on clinical and ECHO features [10]. ECHO evaluation was repeated at regular intervals. IV paracetamol was used as primary rescue therapy for hsDPA. If hsPDA persisted despite 3 courses of paracetamol therapy, surgical ligation was performed. The non-hsPDA group comprised non-hsPDA preterm infants selected using the same exclusion criteria. Infants with non-hsPDA were excluded from the study.

Continuous and Standard Intermittent Bolus Infusion of Paracetamol IV paracetamol therapy was delivered as primary rescue pharmacological treatment to all neonates who had hsPDA during the study period. Standard IV intermittent bolus paracetamol therapy was administered in the form of 15 mg/kg doses as 1-hour infusions every 6 hours for 5 days, while continuous IV paracetamol infusion therapy was administered as a 60 mg/kg/day dose continuously for 5 days (Parol, Atabay Ilac Kimya San., Istanbul, Turkey). ALT and AST levels were analyzed before and after treatment . Infants received standard IV intermittent bolus paracetamol between January 1 and April 31, 2018, and continuous IV infusion paracetamol between May 1 - August 31, 2018 for hsPDA medical treatment. Therefore, eligible infants were divided into two groups as the standard IV intermittent bolus infusion group and the continuous IV infusion group.

• Study Type: Observational
• Enrollment (Actual): 138

Contacts and Locations

Study Locations

• Turkey
  • Ankara, Turkey, 06130
    • Ufuk Cakir

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 1 month (Child)
• Accepts Healthy Volunteers: N/A
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Preterm preterms with birth weight (BW) ≤1500 g and gestational age (GA) ≤32 weeks will be included in the study.

Description

Inclusion Criteria:

birth weight (BW) ≤1500 g and gestational age (GA) ≤32 weeks at birth

Exclusion Criteria:

birth weight (BW) >1500 g and gestational age (GA) >32 weeks at birth

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
standard IV intermittent bolus infusion group	Drug: Paracetamol Infusion; Continuous and Standard Intermittent Boluses Paracetamol Infusion
continuousIV intermittent bolus infusion group	Drug: Paracetamol Infusion; Continuous and Standard Intermittent Boluses Paracetamol Infusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Patent Ductus Arteriosus	PDA-related morbidities, multiple paracetamol courses, and PDA ligation	6 months

Collaborators and Investigators

• Sponsor: Ankara University

Publications and helpful links

General Publications

• Cakir U, Tayman C, Karacaglar NB, Beser E, Ceran B, Unsal H. Comparison of the effect of continuous and standard intermittent bolus paracetamol infusion on patent ductus arteriosus. Eur J Pediatr. 2021 Feb;180(2):433-440. doi: 10.1007/s00431-020-03822-1. Epub 2020 Sep 29.

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2019
• Primary Completion (Actual): August 1, 2019
• Study Completion (Actual): January 6, 2020

Study Registration Dates

• First Submitted: July 9, 2020
• First Submitted That Met QC Criteria: July 9, 2020
• First Posted (Actual): July 14, 2020

Study Record Updates

• Last Update Posted (Actual): July 14, 2020
• Last Update Submitted That Met QC Criteria: July 9, 2020
• Last Verified: July 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Congenital Abnormalities; Heart Defects, Congenital; Cardiovascular Abnormalities; Ductus Arteriosus, Patent; Physiological Effects of Drugs; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Analgesics, Non-Narcotic; Antipyretics; Acetaminophen
• Other Study ID Numbers: 113/2019

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No