Co-administration of Acetaminophen With Ibuprofen to Improve Duct-Related Outcomes in Extremely Premature Infants

NCT ID: NCT05340582

Last Updated: 2025-12-04

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE2

Total Enrollment

310 participants

Study Classification

INTERVENTIONAL

Study Start Date

2022-12-12

Study Completion Date

2027-04-30

Brief Summary

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Patent ductus arteriosus (PDA), the most common cardiovascular complication of prematurity, is associated with higher mortality and morbidities in extremely low gestational age neonates (ELGANs, \< 27+0 weeks). Ibuprofen and acetaminophen, which act by reducing prostaglandin synthesis, are the most commonly used first and second line agents for PDA treatment across Canada. However, initial treatment failure with monotherapy is a major problem, occurring in \>60% ELGANs. Treatment failure is associated with worsening rates of mortality and bronchopulmonary dysplasia (BPD), while early treatment success can achieve rates comparable to neonates without PDA. Treatment failure resulting in prolonged disease exposure is thought to be a major contributor. Recently, combination therapy with acetaminophen and ibuprofen has emerged as a new treatment regime. Acetaminophen exerts anti-prostaglandin effect through a different receptor site than ibuprofen, providing a biological rationale for their synergistic action.

The objective of this study is to evaluate the clinical impact, efficacy and safety of combination regime (Ibuprofen + IV Acetaminophen) for the first treatment course for PDA in ELGANs vs. Ibuprofen alone (current standard treatment).

Detailed Description

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Conditions

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Patent Ductus Arteriosus After Premature Birth

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Pragmatic, multicenter, double-blinded, placebo controlled, parallel, two-armed, superiority randomized trial comparing two treatment regimens for the first treatment course of PDA in ELGANs
Primary Study Purpose

TREATMENT

Blinding Strategy

TRIPLE

Participants Investigators Outcome Assessors
Double-blinded

Study Groups

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Combination Therapy

Intravenous or enteral ibuprofen, as decided by clinical team, in the standard clinical dose used in participating NICUs (typically, for neonates \< 7 days old - 10 mg/kg/dose on day 1, 5 mg/kg/dose q24h on days 2 and 3; for neonates \> 7 days old - 20 mg/kg/dose on day 1, 10 mg/kg/dose q24h on days 2 and 3) And study drug (intravenous acetaminophen 15 mg/kg/dose IV q6h for 3 days).

Group Type EXPERIMENTAL

Acetaminophen Injection

Intervention Type DRUG

Acetaminophen injection solution 1000 mg/100 mL (10 mg/mL) latex-free plastic bag - dosage for this protocol is 15mg/kg/dose IV four times a day for 3 days

Ibuprofen 20 mg/mL oral suspension or Ibuprofen lysine 10 mg/mL injection solution (Neoprofen)

Intervention Type DRUG

Ibuprofen is not a study drug - standard of care in participating NICUs in the standard clinical dose for neonates (typically, for neonates \< 7 days old - 10 mg/kg/dose on day 1, 5 mg/kg/dose q24h on days 2 and 3; for neonates \> 7 days old - 20 mg/kg/dose on day 1, 10 mg/kg/dose q24h on days 2 and 3)

Standard Clinical Practice - Monotherapy

Intravenous or enteral ibuprofen, as decided by clinical team, in the standard clinical dose used in participating NICUs (typically, for neonates \< 7 days old - 10 mg/kg/dose on day 1, 5 mg/kg/dose q24h on days 2 and 3; for neonates \> 7 days old - 20 mg/kg/dose on day 1, 10 mg/kg/dose q24h on days 2 and 3) And Placebo \[(0.9% saline IV q6h for 3 days).

Group Type PLACEBO_COMPARATOR

Ibuprofen 20 mg/mL oral suspension or Ibuprofen lysine 10 mg/mL injection solution (Neoprofen)

Intervention Type DRUG

Ibuprofen is not a study drug - standard of care in participating NICUs in the standard clinical dose for neonates (typically, for neonates \< 7 days old - 10 mg/kg/dose on day 1, 5 mg/kg/dose q24h on days 2 and 3; for neonates \> 7 days old - 20 mg/kg/dose on day 1, 10 mg/kg/dose q24h on days 2 and 3)

Sodium chloride 0.9% injection

Intervention Type OTHER

Placebo- IV q6h for 3 days

Interventions

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Acetaminophen Injection

Acetaminophen injection solution 1000 mg/100 mL (10 mg/mL) latex-free plastic bag - dosage for this protocol is 15mg/kg/dose IV four times a day for 3 days

Intervention Type DRUG

Ibuprofen 20 mg/mL oral suspension or Ibuprofen lysine 10 mg/mL injection solution (Neoprofen)

Ibuprofen is not a study drug - standard of care in participating NICUs in the standard clinical dose for neonates (typically, for neonates \< 7 days old - 10 mg/kg/dose on day 1, 5 mg/kg/dose q24h on days 2 and 3; for neonates \> 7 days old - 20 mg/kg/dose on day 1, 10 mg/kg/dose q24h on days 2 and 3)

Intervention Type DRUG

Sodium chloride 0.9% injection

Placebo- IV q6h for 3 days

Intervention Type OTHER

Eligibility Criteria

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Inclusion Criteria

* Preterm infants born \<27+0 weeks gestational age
* Permission given by the attending clinician to approach and then consent obtained from parents
* Diagnosis of PDA ≥ 1.5 mm on echocardiography with unrestrictive predominantly left to right shunt
* Designated to receive first treatment course with intravenous or enteral ibuprofen, as decided by the attending team.

Exclusion Criteria

* Chromosomal anomaly
* Pre-treatment renal dysfunction defined as urine output \< 1ml/kg/hour for the previous 24 hours or serum creatinine \> 100 micromol/L
* Pre-treatment hepatic dysfunction defined as serum aminotransferase (ALT) \> 100 units/L94
* Platelet count \<50,000 per microliter
* Permission denied by the attending clinician to approach parents
* Parental consent not available
* Previous exposure to PDA medical treatment with any drug (prophylactic indomethacin use for prevention of intraventricular hemorrhage will not be considered as PDA treatment).
Maximum Eligible Age

27 Weeks

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Sunnybrook Health Sciences Centre

OTHER

Sponsor Role collaborator

McMaster Children's Hospital

OTHER

Sponsor Role collaborator

The Rotunda Hospital

OTHER

Sponsor Role collaborator

John Hunter Hospital

OTHER_GOV

Sponsor Role collaborator

Royal Alexandra Hospital

OTHER

Sponsor Role collaborator

Centre Hospitalier de l'Universite Laval (CHUL)

UNKNOWN

Sponsor Role collaborator

Royal North Shore Hospital

OTHER

Sponsor Role collaborator

Prince of Wales Hospital, Shatin, Hong Kong

OTHER

Sponsor Role collaborator

Mount Sinai Hospital, Canada

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Amish Jain, MD PhD

Role: PRINCIPAL_INVESTIGATOR

MOUNT SINAI HOSPITAL

Locations

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John Hunter Hospital

Newcastle, New South Wales, Australia

Site Status ACTIVE_NOT_RECRUITING

Royal North Shore Hospital

St Leonards, New South Wales, Australia

Site Status RECRUITING

Royal Alexandra Hospital

Edmonton, Ontario, Canada

Site Status RECRUITING

McMaster Children's Hospital

Hamilton, Ontario, Canada

Site Status RECRUITING

Sunnybrook Health Sciences Centre

Toronto, Ontario, Canada

Site Status RECRUITING

Mount Sinai Hospital

Toronto, Ontario, Canada

Site Status RECRUITING

Centre Hospitalier de l'Université Laval

Québec, Quebec, Canada

Site Status NOT_YET_RECRUITING

Prince of Wales Hospital

Shatin, NT, Hong Kong

Site Status NOT_YET_RECRUITING

The Rotunda Hospital

Dublin, , Ireland

Site Status ACTIVE_NOT_RECRUITING

Countries

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Australia Canada Hong Kong Ireland

Central Contacts

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Laura Thomas, MSc

Role: CONTACT

416-586-4800 ext. 172060

Facility Contacts

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Dany Weisz, MD, MSc

Role: primary

Other Identifiers

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CTO 1875

Identifier Type: -

Identifier Source: org_study_id

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