Paracetamol in Patent Ductus Arteriosus

Ductus Arteriosus, Patent Clinical Trial

Official title:

Efficacy and Safety of Paracetamol in Comparison to Ibuprofen for Patent Ductus Arteriosus Treatment in Preterm Infants: A Randomized, Open Label, Comparator-controlled, Prospective Study

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02422966
• Other study ID #: 044CF13273
• Status: Completed
• Phase: Phase 2
• Start date: December 2015
• Est. completion date: April 2019

Study information

• Verified date: July 2019
• Source: Aziende Chimiche Riunite Angelini Francesco S.p.A
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of the study is to assess the efficacy and safety of paracetamol in comparison to ibuprofen in the treatment of patent ductus arteriosus (PDA) in preterm infants.

Description:

Although patency of the ductus arteriosus is essential for fetal circulation, the postnatal ductal closure is critical for postnatal circulatory adaptation. In premature infants the circulating prostaglandin levels are higher than at term, and respiratory difficulties may lead to a state of hypoxia, which contribute to the failure of the ductus closure. Recently, an incidental finding in one preterm infant led to look at paracetamol, one of the most common drugs available, as an alternative therapeutic approach to ductal closure. If paracetamol is proven to be effective, it could become the treatment of choice for the management of PDA, mainly due to its more favorable safety profile.

Although the recent results available in the literature demonstrates an highly success rate in ductal closure with paracetamol, all case studies are not powered to show efficacy of paracetamol for PDA closure. Further prospective randomized-controlled trials are needed to evaluate the efficacy of paracetamol versus ibuprofen for the closure of PDA.

If paracetamol is indeed proven to be effective, it could become the treatment of choice for the management of PDA, mainly due to its more favorable side effect profile. In order to test this hypothesis, a randomized, open label, parallel groups, comparator controlled, multicentre, prospective study is proposed.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 110
• Est. completion date: April 2019
• Est. primary completion date: January 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 25 Weeks to 31 Weeks

Eligibility

Inclusion Criteria:

1. Male or female preterm infants with no limitation of race.

2. Gestational age 25(+0) - 31(+6) weeks.

3. Age 24-72 hours.

4. Echocardiographic evidence of hemodynamically significant patent ductus arteriosus at the first 24-72 hours of life.

The diagnosis of hemodynamically significant PDA requiring treatment will be made by echocardiographic demonstration of a ductal left-to-right shunt, with a left atrium-to-aortic root ratio >1.3 or a ductal size >1.5 mm and excluding the cases in which the closing flow pattern suggests a restrictive PDA.

5. Willingness of the parents/legally authorized representative/child to sign the Consent Informed Form.

Exclusion Criteria:

1. Outborn patients.

2. Major congenital anomalies, including but not limited to congenital heart defects, Down syndrome newborn and/or new born suffering from congenital anomalies diagnosed during the fetal period.

3. Known positive HIV and/or known positive Hepatitis C Virus newborn's mother.

4. Life threatening infection, complicated or not by multiple organ dysfunction and failure syndrome.

5. Fetal hydrops.

6. Pulmonary hypertension diagnosed in the first 24-48 hours of life by means of heart ultrasound when the presence of a right-to-left shunt through the foramen ovale or ductus arteriosus is demonstrated, or when the estimated pulmonary pressure, in terms of the tricuspid regurgitation jet, is greater than two-thirds of the systemic arterial pressure.

7. Grade 3 or 4 intraventricular haemorrhage (IVH).

8. Urine output <1 ml/kg of body weight/h during a 24 h collection period or urine output <0.5 ml/kg of body weight/h in case it is measured at 24 hours of life of newborn.

9. Serum creatinine concentration > 1.5 mg/dl (132 µmol/l).

10. Platelet count < 50,000/mm3.

11. Major bleeding, as revealed by hematuria, or blood in the endotracheal aspirate, gastric aspirate, or stools, or consistent oozing of blood from puncture sites.

12. Severe liver failure, defined as elevated liver enzymes (ALT/Glutamate-Pyruvate Transaminase and Aspartate aminotransferase/GOT) > 2 times the upper boundary of the normal range. For this kind of population the following normal ranges will be considered [Rosenthal, 1997]:

• ALT/Glutamate-pyruvate transaminase: 6-50 U/L

• Aspartate aminotransferase/GOT: 35-140 U/L

13. Medical need of administering other Nonsteroidal Antiinflammatory Drug (NSAID) different from ibuprofen.

14. Participation to another trial involving any investigational drug.

Related Conditions & MeSH terms

• Ductus Arteriosus, Patent

Intervention

Drug:
• Paracetamol

• Ibuprofen

Locations

Country	Name	City	State
Italy	Azienda Ospedaliero Universitaria Careggi - Neonatologia e Terapia Intensiva Neonatale	Firenze
Italy	IRCCS "Giannina Gaslini" Genova - Patologia Neonatale e Terapia Intensiva Neonatale	Genova
Italy	Azienda Ospedaliera Istituti Clinici di Perfezionamento (ICP) - Ospedale dei Bambini "Vittore Buzzi" Milano - Neonatologia	Milano
Italy	Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico U.O. di Neonatologia e Terapia Intensiva Neonatale	Milano
Italy	Policlinico Gemelli Roma - UOC Neonatologia	Roma

Sponsors (1)

Lead Sponsor	Collaborator
Aziende Chimiche Riunite Angelini Francesco S.p.A

Country where clinical trial is conducted

Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	success rate in closing PDA using paracetamol in comparison to ibuprofen.	assessed echocardiographically.	at Visit 3 (day 3).
Secondary	number of re-openings.	assessed echocardiographically.	at Follow-up 3 (day 30).
Secondary	success rate in closing PDA after the second treatment course of ibuprofen as rescue medication.	assessed echocardiographically.	at Visit 6 (day 6).
Secondary	success rate of closing PDA after the first day of the first treatment course.	assessed echocardiographically.	at Visit 1 (day 1).
Secondary	success rate of closing PDA after the second day of the first treatment course.	assessed echocardiographically.	at Visit 2 (day 2).
Secondary	incidence of surgical ligation.		at Follow-up 3 (day 30).
Secondary	incidence of renal failure, liver failure and gastrointestinal complications (including isolated intestinal perforation).	assessed by laboratory analysis.	at Follow-up 3 (day 30).
Secondary	incidence of death,		at Follow-up 3 (day 30).
Secondary	incidence of death.		at Follow-up 4 (40 weeks post-conception).
Secondary	incidence of sepsis.		at Follow-up 3 (day 30).
Secondary	hospital-stay duration in Neonatal Intensive Care Unit.		at Follow-up 4 (40 weeks post-conception).
Secondary	occurrence of adverse effects.		at Follow-up 3 (day 30).