Paracetamol (Acetaminophen) for Closure of PDA in Preterm Infants

NCT01755728 | Completed Phase 3

• 1 other identifier: 77-12-HYMC-CTIL
• Study Type: interventional
• Target: 19
• Locations: 1 country
• Sites: 1

Brief Summary

There is a report that acetaminophen may have a role in pharmacological closure of PDA (Patent arterial duct) in preterm infants. The investigators conducted this open label non randomized and non control study to try to support that report.

Conditions

PDA

Keywords

Paracetamol; Acetaminophen; PDA; Preterm infants

Outcome Measures

Primary Outcomes (1)

• Closure of arterial duct - yes / No

  Echo-cardiogram that will give exact answer to the question: "was the arterial duct closed"?

  1 week

Secondary Outcomes (1)

• Need for surgical closure of arterial duct

  1 week

Other Outcomes (1)

• Death or deterioration

  1 week

Study Arms (5)

No known PDA

NO INTERVENTION

For all infants, we do echo cardiogram study only if they are suspected of having PDA, due to sings and symptoms. Hence, we do not do echo cardiogram study to most of the infants.

Ibuprofen

ACTIVE COMPARATOR

If there is a PDA, that should be treated, and the infant is less than 2 weeks of age, we use ibuprofen, as this is the gold standard in literature.

Drug: Ibuprofen

Surgical closure of PDA

ACTIVE COMPARATOR

Infants with symptomatic PDA, who had to be treated, but could not be treated by ibuprofen, either due to age (\> 2 weeks) or due ibuprofen contraindications (thrombocytopenia or renal failure), whose could not be treated by paracetamol (either because of parents' refuse or because they were on nothing per os protocol due to other disease), for whom surgery was the treatment of choice to close the arterial duct.

Procedure: Closure of PDA

Paracetamol

EXPERIMENTAL

Infants with symptomatic PDA who could not be treated with ibuprofen, and their parents agreed and they could be treated with paracetamol.

Drug: Paracetamol

DA closed spontaneously

NO INTERVENTION

Infants with PDA, who did not get any treatment for it, and the duct was closed spontaneously.

Interventions

Paracetamol DRUG

Per gavage paracetamol 15 mg/kg every 6 hours, for up to 7 days.

Also known as: Acetaminophen

Paracetamol

Ibuprofen DRUG

Per Gavage ibuprofen 10mg/kg x 3/d for up to 5 days Gold standard per literature

Ibuprofen

Closure of PDA PROCEDURE

Open surgery for closure of PDA

Surgical closure of PDA

Eligibility Criteria

• Age: Up to 4 Months
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Preterm infants with symptomatic PDA who could not be treated with ibuprofen

You may not qualify if:

• None

Sponsors & Collaborators

• Hillel Yaffe Medical Center: lead

Study Sites (1)

Neonatal intensive care unit, Hillel Yaffe medical center

Hadera, 38100, Israel

Location

Related Publications (8)

• 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.

  PMID: 22065264 BACKGROUND

• Hammerman C, Bin-Nun A, Kaplan M. Managing the patent ductus arteriosus in the premature neonate: a new look at what we thought we knew. Semin Perinatol. 2012 Apr;36(2):130-8. doi: 10.1053/j.semperi.2011.09.023.

  PMID: 22414884 BACKGROUND

• Oncel MY, Yurttutan S, Uras N, Altug N, Ozdemir R, Ekmen S, Erdeve O, Dilmen U. An alternative drug (paracetamol) in the management of patent ductus arteriosus in ibuprofen-resistant or contraindicated preterm infants. Arch Dis Child Fetal Neonatal Ed. 2013 Jan;98(1):F94. doi: 10.1136/archdischild-2012-302044. Epub 2012 May 18. No abstract available.

  PMID: 22611117 BACKGROUND

• Peterson RG. Consequences associated with nonnarcotic analgesics in the fetus and newborn. Fed Proc. 1985 Apr;44(7):2309-13.

  PMID: 3884385 BACKGROUND

• Rudolph AM. Effects of aspirin and acetaminophen in pregnancy and in the newborn. Arch Intern Med. 1981 Feb 23;141(3 Spec No):358-63. doi: 10.1001/archinte.141.3.358.

  PMID: 7469626 BACKGROUND

• Simbi KA, Secchieri S, Rinaldo M, Demi M, Zanardo V. In utero ductal closure following near-term maternal self-medication with nimesulide and acetaminophen. J Obstet Gynaecol. 2002 Jul;22(4):440-1. doi: 10.1080/01443610220141489. No abstract available.

  PMID: 12521476 BACKGROUND

• Weintraub A, Mankuta D. Dipyrone-induced oligohydramnios and ductus arteriosus restriction. Isr Med Assoc J. 2006 Oct;8(10):722-3. No abstract available.

  PMID: 17125127 BACKGROUND

• Burdan F, Staroslawska E, Szumilo J. Prenatal tolerability of acetaminophen and other over-the-counter non-selective cyclooxygenase inhibitors. Pharmacol Rep. 2012;64(3):521-7. doi: 10.1016/s1734-1140(12)70847-2.

  PMID: 22814005 BACKGROUND

MeSH Terms

Interventions

Acetaminophen; Ibuprofen

Intervention Hierarchy (Ancestors)

Acetanilides; Anilides; Amides; Organic Chemicals; Aniline Compounds; Amines; Phenylpropionates; Acids, Carbocyclic; Carboxylic Acids

Study Officials

• Erez Nadir, MD

  Hillel Yaffe medical center, Hadera, Israel

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER GOV
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Senior neonatologist

Study Record Dates

• First Submitted: December 16, 2012
• First Posted: December 24, 2012
• Study Start: January 1, 2013
• Primary Completion: December 31, 2018
• Study Completion: December 31, 2018
• Last Updated: August 6, 2019

Record last verified: 2019-08

Data Sharing

• IPD Sharing: Will not share

Locations

IL (1)