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Trial record 1 of 1 for:    NCT02422966
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Paracetamol in Patent Ductus Arteriosus

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ClinicalTrials.gov Identifier: NCT02422966
Recruitment Status : Completed
First Posted : April 22, 2015
Last Update Posted : July 12, 2019
Sponsor:
Information provided by (Responsible Party):
Aziende Chimiche Riunite Angelini Francesco S.p.A

Brief 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.

Condition or disease Intervention/treatment Phase
Ductus Arteriosus, Patent Drug: Paracetamol Drug: Ibuprofen Phase 2

Detailed 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.


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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 110 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : December 2015
Actual Primary Completion Date : January 2019
Actual Study Completion Date : April 2019


Arm Intervention/treatment
Experimental: Paracetamol
Paracetamol intravenous solution 15 mg/kg (corresponding to 1.5 ml/kg) per dose every 6 hours for 3 days, for a total amount of 12 doses.
Drug: Paracetamol
Other Name: Acetaminophen

Active Comparator: Ibuprofen
Ibuprofen intravenous solution at an initial dose of 10 mg/kg, followed by 5 mg/kg at 24 and 5 mg/kg at 48 h.
Drug: Ibuprofen



Primary Outcome Measures :
  1. success rate in closing PDA using paracetamol in comparison to ibuprofen. [ Time Frame: at Visit 3 (day 3). ]
    assessed echocardiographically.


Secondary Outcome Measures :
  1. number of re-openings. [ Time Frame: at Follow-up 3 (day 30). ]
    assessed echocardiographically.

  2. success rate in closing PDA after the second treatment course of ibuprofen as rescue medication. [ Time Frame: at Visit 6 (day 6). ]
    assessed echocardiographically.

  3. success rate of closing PDA after the first day of the first treatment course. [ Time Frame: at Visit 1 (day 1). ]
    assessed echocardiographically.

  4. success rate of closing PDA after the second day of the first treatment course. [ Time Frame: at Visit 2 (day 2). ]
    assessed echocardiographically.

  5. incidence of surgical ligation. [ Time Frame: at Follow-up 3 (day 30). ]
  6. incidence of renal failure, liver failure and gastrointestinal complications (including isolated intestinal perforation). [ Time Frame: at Follow-up 3 (day 30). ]
    assessed by laboratory analysis.

  7. incidence of death, [ Time Frame: at Follow-up 3 (day 30). ]
  8. incidence of death. [ Time Frame: at Follow-up 4 (40 weeks post-conception). ]
  9. incidence of sepsis. [ Time Frame: at Follow-up 3 (day 30). ]
  10. hospital-stay duration in Neonatal Intensive Care Unit. [ Time Frame: at Follow-up 4 (40 weeks post-conception). ]
  11. occurrence of adverse effects. [ Time Frame: at Follow-up 3 (day 30). ]


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Ages Eligible for Study:   25 Weeks to 31 Weeks   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02422966


Locations
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Italy
Azienda Ospedaliero Universitaria Careggi - Neonatologia e Terapia Intensiva Neonatale
Firenze, Italy, 50134
IRCCS "Giannina Gaslini" Genova - Patologia Neonatale e Terapia Intensiva Neonatale
Genova, Italy, 16147
Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico U.O. di Neonatologia e Terapia Intensiva Neonatale
Milano, Italy, 20122
Azienda Ospedaliera Istituti Clinici di Perfezionamento (ICP) - Ospedale dei Bambini "Vittore Buzzi" Milano - Neonatologia
Milano, Italy, 20154
Policlinico Gemelli Roma - UOC Neonatologia
Roma, Italy, 00168
Sponsors and Collaborators
Aziende Chimiche Riunite Angelini Francesco S.p.A

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Aziende Chimiche Riunite Angelini Francesco S.p.A
ClinicalTrials.gov Identifier: NCT02422966     History of Changes
Other Study ID Numbers: 044CF13273
First Posted: April 22, 2015    Key Record Dates
Last Update Posted: July 12, 2019
Last Verified: July 2019
Additional relevant MeSH terms:
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Ductus Arteriosus, Patent
Heart Defects, Congenital
Cardiovascular Abnormalities
Cardiovascular Diseases
Heart Diseases
Congenital Abnormalities
Acetaminophen
Ibuprofen
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Antipyretics
Anti-Inflammatory Agents, Non-Steroidal
Anti-Inflammatory Agents
Antirheumatic Agents
Cyclooxygenase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action