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Paracetamol vs Ibuprofen for PDA Closure in Preterm Infants. (PARIDA)

Primary Purpose

Ductus Arteriosus Patent, Respiratory Distress Syndrome

Status

Suspended

Phase

Phase 2

Locations

Italy

Study Type

Interventional

Intervention

Intravenous paracetamol

Intravenous ibuprofen

About this trial

This is an interventional treatment trial for Ductus Arteriosus Patent focused on measuring Patent ductus arteriosus, Preterm infant, Paracetamol, Ibuprofen

Eligibility Criteria

36 Hours - 72 Hours (Child)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

inborn neonates
preterm neonates ≤ 31+ 6 days weeks gestation
newborns with HsPDA
parental written informed consent for participation in the study must be obtained

Exclusion Criteria:

Serum creatinine concentration greater than 1,5 mg/dl (132MMole/L)
Urine output less than 1 ml/Kg/h
Severe IVH (> grade II according to Volpe classification)
Clinical bleeding tendency (as revealed by hematuria, blood in the gastric aspirate or in the stools, blood in the endotracheal tube aspirate)
Necrotizing enterocolitis or marked abdominal distention with gastric bile residuals
Thrombocyte count of less than 50.000/mm3
Proved Sepsis
Severe coagulopathy or liver failure
Evidence of severe birth asphyxia, that is an APGAR score below 5 at 5 minutes of age and/or umbilical arterial pH < 7.0
Known genetic or chromosomal disorders
Participation in another clinical trial of any placebo, drug, biological, or device conducted under the provisions of a protocol.

Sites / Locations

NICU, Women's and Children's Health Department, Azienda Ospedaliera-University of Padua

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

paracetamol

Intravenous ibuprofen

Arm Description

Boluses of intravenous paracetamol at 15 mg/Kg four time a day for three consecutive days.

Standard boluses of ibuprofen at 10-5-5-mg/Kg/dose once a day for three consecutive days.

Outcomes

Primary Outcome Measures

PDA pharmacological closure

The rate of ductal closure after the first and second course of pharmacological treatment. (PDA diagnosed by ECHO criteria) in paracetamol versus ibuprofen group

Secondary Outcome Measures

Oliguria

Rate of oliguria defined as a reduction on urine output less than 1ml/Kg/h,

Full Information

NCT ID

NCT02056223

First Posted

February 3, 2014

Last Updated

October 30, 2019

Sponsor

University of Padova

1. Study Identification

Unique Protocol Identification Number

NCT02056223

Brief Title

Paracetamol vs Ibuprofen for PDA Closure in Preterm Infants.

Acronym

PARIDA

Official Title

Paracetamol Versus Ibuprofen for Patent Ductus Arteriosus Closure in Preterm Infants. A Prospective, Randomized, Controlled, Double Blind, Multicenter Clinical Trial.

Study Type

Interventional

2. Study Status

Record Verification Date

October 2019

Overall Recruitment Status

Suspended

Why Stopped

We enrolled only 53 patients

Study Start Date

January 9, 2017 (Actual)

Primary Completion Date

October 31, 2019 (Anticipated)

Study Completion Date

October 31, 2019 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

University of Padova

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

Current pharmacological options to treat an hemodynamically significant PDA (HsPDA) in preterm infants are limited to non-selective cyclo-oxygenase (COX) inhibitors, indomethacin or ibuprofen. Recently paracetamol exposure has been reported to successful closure of PDA. Aim of this randomized double-blind controlled study is to compare the efficacy and the safety of standard PDA treatment ibuprofen versus paracetamol-experimental treatment . We hypothesize that paracetamol is more effective than ibuprofen in closing PDA, perhaps ameliorating the safety profile of the pharmacological treatment.

Detailed Description

The objective of this trial is to compare the efficacy and safety of 2 therapeutic regimens for PDA treatment in a population of preterm newborns of gestational age (GA) <31+6 weeks with respiratory distress syndrome (RDS) and HsPDA: Group A: experimental boluses of paracetamol at 15 mg/Kg four time a day for three consecutive days. Group B: standard boluses of ibuprofen at 10-5-5-mg/Kg/dose once a day for three consecutive days. The primary objective of the study is: to evaluate the efficacy of paracetamol versus standard ibuprofen regimen, by comparing the rate of ductal closure after the first and second course of pharmacological treatment. (PDA diagnosed by ECHO criteria) The secondary objective of the study is: to evaluate the safety of the above 2 therapeutic regimens in term of incidence of transient renal impairment, intraventricular hemorrhage (IVH) or other bleeding disorders, necrotizing enterocolitis (NEC) and isolated bowel perforation (without signs of NEC), incidence of sign of liver toxicity.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Ductus Arteriosus Patent, Respiratory Distress Syndrome

Keywords

Patent ductus arteriosus, Preterm infant, Paracetamol, Ibuprofen

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2, Phase 3

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

120 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

paracetamol

Arm Type

Experimental

Arm Description

Boluses of intravenous paracetamol at 15 mg/Kg four time a day for three consecutive days.

Arm Title

Intravenous ibuprofen

Arm Type

Active Comparator

Arm Description

Standard boluses of ibuprofen at 10-5-5-mg/Kg/dose once a day for three consecutive days.

Intervention Type

Drug

Intervention Name(s)

Intravenous paracetamol

Other Intervention Name(s)

Paracetamol i.v.

Intervention Description

15 mg/Kg every 6 hours for three days

Intervention Type

Drug

Intervention Name(s)

Intravenous ibuprofen

Other Intervention Name(s)

Pedea i.v.

Intervention Description

10 -5-5 mg/Kg once a day for three days

Primary Outcome Measure Information:

Title

PDA pharmacological closure

Description

The rate of ductal closure after the first and second course of pharmacological treatment. (PDA diagnosed by ECHO criteria) in paracetamol versus ibuprofen group

Time Frame

Partecipants will be evaluated at the end of first and second course, at an expected avarage of 8 days of life (DOL)

Secondary Outcome Measure Information:

Title

Oliguria

Description

Rate of oliguria defined as a reduction on urine output less than 1ml/Kg/h,

Time Frame

In the first 14 days of life

Other Pre-specified Outcome Measures:

Title

Necrotizing enterocolitis (NEC)

Description

Rate of NEC in the paracetamol and ibuprofen group

Time Frame

In the first 14 days of life

Title

Intraventricular haemorrhage (IVH) or death

Description

Rate of intraventricular haemorrhage (IVH) or death within 28 days of life (composite outcome).

Time Frame

Within 28 days of life

10. Eligibility

Sex

All

Minimum Age & Unit of Time

36 Hours

Maximum Age & Unit of Time

72 Hours

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: inborn neonates preterm neonates ≤ 31+ 6 days weeks gestation newborns with HsPDA parental written informed consent for participation in the study must be obtained Exclusion Criteria: Serum creatinine concentration greater than 1,5 mg/dl (132MMole/L) Urine output less than 1 ml/Kg/h Severe IVH (> grade II according to Volpe classification) Clinical bleeding tendency (as revealed by hematuria, blood in the gastric aspirate or in the stools, blood in the endotracheal tube aspirate) Necrotizing enterocolitis or marked abdominal distention with gastric bile residuals Thrombocyte count of less than 50.000/mm3 Proved Sepsis Severe coagulopathy or liver failure Evidence of severe birth asphyxia, that is an APGAR score below 5 at 5 minutes of age and/or umbilical arterial pH < 7.0 Known genetic or chromosomal disorders Participation in another clinical trial of any placebo, drug, biological, or device conducted under the provisions of a protocol.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Paola Lago, MD

Organizational Affiliation

Women's and Children's Health Department- AO- University of Padua

Official's Role

Principal Investigator

Facility Information:

Facility Name

NICU, Women's and Children's Health Department, Azienda Ospedaliera-University of Padua

City

Padua

ZIP/Postal Code

35128

Country

Italy

12. IPD Sharing Statement

Citations:

PubMed Identifier

23258386

Citation

Oncel MY, Yurttutan S, Degirmencioglu H, Uras N, Altug N, Erdeve O, Dilmen U. Intravenous paracetamol treatment in the management of patent ductus arteriosus in extremely low birth weight infants. Neonatology. 2013;103(3):166-9. doi: 10.1159/000345337. Epub 2012 Dec 19.

Results Reference

result

PubMed Identifier

22065264

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.

Results Reference

result

PubMed Identifier

22611117

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.

Results Reference

result

PubMed Identifier

21317433

Citation

Allegaert K, Palmer GM, Anderson BJ. The pharmacokinetics of intravenous paracetamol in neonates: size matters most. Arch Dis Child. 2011 Jun;96(6):575-80. doi: 10.1136/adc.2010.204552. Epub 2011 Feb 13.

Results Reference

result

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Paracetamol vs Ibuprofen for PDA Closure in Preterm Infants.

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