Paracetamol (Acetaminophen) for Closure of PDA in Preterm Infants

PDA Clinical Trial

Official title:

Paracetamol (Acetaminophen) for Closure of PDA in Preterm Infants

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01755728
• Other study ID #: 77-12-HYMC-CTIL
• Status: Completed
• Phase: Phase 3
• Start date: January 1, 2013
• Est. completion date: December 31, 2018

Study information

• Verified date: August 2019
• Source: Hillel Yaffe Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

In-uteri, the arterial duct connects between the aorta and the main pulmonary artery, thus bypassing the lungs. Since the high pulmonary pressure and the low systemic pressure, the shunt trough the arterial duct in that time is right to left.

After birth, systemic pressure rises and pulmonary pressure declines. As oxygen saturation rises, and prostaglandin secretion, the arterial duct closes, usually. In preterm infants, the arterial duct may remain open after birth. At this tume the shunt would be left to right, that would cause pulmonary congestion, and systemic hypoperfusion.

Ibuprofen is the treatment of choice for PDA in preterm infants. Yet, ibuprofen is not effective after two weeks of age. Moreover, there are situations that prevent treatment with ibuprofen, such as thrombocytopenia or renal failure. Surgical closure of arterial duct is an alternative treatment, if ibuprofen is contraindicated, or if it fails.

Lastly, there was a report that acetaminophen may have a role in pharmacological closure of PDA in preterm infants.

The investigators conducted this open label non randomized and non control study to try to support that report.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 19
• Est. completion date: December 31, 2018
• Est. primary completion date: December 31, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 4 Months

Eligibility

Inclusion Criteria:

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

Exclusion Criteria:

• None

Related Conditions & MeSH terms

• PDA

Intervention

Drug:
• Paracetamol
Per gavage paracetamol 15 mg/kg every 6 hours, for up to 7 days.
• Ibuprofen
Per Gavage ibuprofen 10mg/kg x 3/d for up to 5 days Gold standard per literature

Procedure:
• Closure of PDA
Open surgery for closure of PDA

Locations

Country	Name	City	State
Israel	Neonatal intensive care unit, Hillel Yaffe medical center	Hadera

Sponsors (1)

Lead Sponsor	Collaborator
Hillel Yaffe Medical Center

Country where clinical trial is conducted

Israel, 

References & Publications (8)

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. Review. — View Citation

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. Review. — View 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. — View Citation

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. — View Citation

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

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. — View Citation

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. — View Citation

Weintraub A, Mankuta D. Dipyrone-induced oligohydramnios and ductus arteriosus restriction. Isr Med Assoc J. 2006 Oct;8(10):722-3. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Death or deterioration	The infant state deteriorates so quickly that it will die, either because of complication of the arterial duct, or because other causes, such as sepsis, metabolic disorder, etc...	1 week
Primary	Closure of arterial duct - yes / No	Echo-cardiogram that will give exact answer to the question: "was the arterial duct closed"?	1 week
Secondary	Need for surgical closure of arterial duct	The clinical state of the infant will guide the team to ask the parents and the chest surgeon to surgically close the arterial duct	1 week