Clinical trial NCT01755728: Paracetamol (Acetaminophen) for Closure of PDA in Preterm Infants
Official title: Paracetamol (Acetaminophen) for Closure of PDA in Preterm Infants
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: PDA
Keywords: Paracetamol
Acetaminophen
PDA
Preterm infants
Lead sponsor: Hillel Yaffe Medical Center
Sponsor class: OTHER_GOV
First posted: 2012-12-24
Enrollment: 19
Sex: ALL
Maximum age (years): 4
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Detailed 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.

Eligibility criteria: Inclusion Criteria:

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

Exclusion Criteria:

* None

Primary outcomes:
measure: Closure of arterial duct - yes / No
timeFrame: 1 week
Secondary outcomes:
measure: Need for surgical closure of arterial duct
timeFrame: 1 week
Other outcomes:
measure: Death or deterioration
timeFrame: 1 week
Locations:
city: Hadera
country: Israel
facility: Neonatal intensive care unit, Hillel Yaffe medical center
Study officials:
affiliation: Hillel Yaffe medical center, Hadera, Israel
name: Erez Nadir, MD
role: PRINCIPAL_INVESTIGATOR
References:
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.
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.
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. No abstract available.
citation: Peterson RG. Consequences associated with nonnarcotic analgesics in the fetus and newborn. Fed Proc. 1985 Apr;44(7):2309-13.
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. doi: 10.1001/archinte.141.3.358.
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. doi: 10.1080/01443610220141489. No abstract available.
citation: Weintraub A, Mankuta D. Dipyrone-induced oligohydramnios and ductus arteriosus restriction. Isr Med Assoc J. 2006 Oct;8(10):722-3. No abstract available.
citation: 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.