Paracetamol (Acetaminophen) for Closure of PDA in Preterm Infants

This study is currently recruiting participants. (see Contacts and Locations)
Verified November 2013 by Hillel Yaffe Medical Center
Sponsor:
Information provided by (Responsible Party):
Erez Nadir, MD, Hillel Yaffe Medical Center
ClinicalTrials.gov Identifier:
NCT01755728
First received: December 16, 2012
Last updated: November 7, 2013
Last verified: November 2013
  Purpose

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.


Condition Intervention Phase
PDA
Drug: Paracetamol
Drug: Ibuprofen
Procedure: Closure of PDA
Phase 3

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Paracetamol (Acetaminophen) for Closure of PDA in Preterm Infants

Resource links provided by NLM:


Further study details as provided by Hillel Yaffe Medical Center:

Primary Outcome Measures:
  • Closure of arterial duct - yes / No [ Time Frame: 1 week ] [ Designated as safety issue: No ]
    Echo-cardiogram that will give exact answer to the question: "was the arterial duct closed"?


Secondary Outcome Measures:
  • Need for surgical closure of arterial duct [ Time Frame: 1 week ] [ Designated as safety issue: No ]
    The clinical state of the infant will guide the team to ask the parents and the chest surgeon to surgically close the arterial duct


Other Outcome Measures:
  • Death or deterioration [ Time Frame: 1 week ] [ Designated as safety issue: No ]
    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...


Estimated Enrollment: 20
Study Start Date: January 2013
Estimated Study Completion Date: December 2017
Estimated Primary Completion Date: December 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
No Intervention: No known PDA
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.
Active Comparator: Ibuprofen
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
Per Gavage ibuprofen 10mg/kg x 3/d for up to 5 days Gold standard per literature
Other Name: (None)
Active Comparator: Surgical closure of PDA
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
Open surgery for closure of PDA
Other Name: (None)
Experimental: Paracetamol
Infants with symptomatic PDA who could not be treated with ibuprofen, and their parents agreed and they could be treated with paracetamol.
Drug: Paracetamol
Per gavage paracetamol 15 mg/kg every 6 hours, for up to 7 days.
Other Name: Acetaminophen
No Intervention: DA closed spontaneously
Infants with PDA, who did not get any treatment for it, and the duct was closed spontaneously.

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

Ages Eligible for Study:   up to 4 Months
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

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

Exclusion Criteria:

  • None
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01755728

Contacts
Contact: Erez Nadir, MD +97246304320 erezn@hy.health.gov.il
Contact: Michael Feldman, MD +97246304320 feldman@hy.health.gov.il

Locations
Israel
Neonatal intensive care unit, Hillel Yaffe medical center Recruiting
Hadera, Israel, 38100
Contact: Erez Nadir, MD    +97246304320    erezn@hy.health.gov.il   
Contact: Michael Feldman, MD    +97246304320    feldman@hy.health.gov.il   
Principal Investigator: Erez Nadir, MD         
Sponsors and Collaborators
Hillel Yaffe Medical Center
Investigators
Principal Investigator: Erez Nadir, MD Hillel Yaffe medical center, Hadera, Israel
  More Information

Publications:

Responsible Party: Erez Nadir, MD, Senior neonatologist, Hillel Yaffe Medical Center
ClinicalTrials.gov Identifier: NCT01755728     History of Changes
Other Study ID Numbers: 77-12-HYMC-CTIL
Study First Received: December 16, 2012
Last Updated: November 7, 2013
Health Authority: Israel: Ministry of Health

Keywords provided by Hillel Yaffe Medical Center:
Paracetamol
Acetaminophen
PDA
Preterm infants

Additional relevant MeSH terms:
Acetaminophen
Ibuprofen
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Central Nervous System Agents
Therapeutic Uses
Antipyretics
Anti-Inflammatory Agents, Non-Steroidal
Anti-Inflammatory Agents
Antirheumatic Agents
Cyclooxygenase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on September 18, 2014