ClinicalTrials.gg
RecruitingNCT05340582Updated Sep 15, 2026

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

A Phase 2 interventional study of Acetaminophen Injection and Ibuprofen 20 mg/mL oral suspension or Ibuprofen lysine 10 mg/mL injection solution (Neoprofen) in Patent Ductus Arteriosus After Premature Birth, sponsored by Mount Sinai Hospital, Canada. Recruiting at 9 sites in 4 countries. Open to participants aged Up to 27 Weeks. Per ClinicalTrials.gov, last updated 2026-09-15.

Sponsored by Mount Sinai Hospital, Canada · Phase 2, Interventional, and Treatment

From the registry’s dates

  • Started Dec 2022; still recruiting 3 years 10 months later.
Phase
Phase 2
Study type
Interventional
Enrollment
310
Allocation
Randomized
Ages
Up to 27 Weeks
Sex
All
01

Study summary

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).

The study will also evaluate the effects of combination regime vs. ibuprofen alone on neurodevelopmental outcomes at 18-30 months corrected age.

02

Conditions studied

  • Patent Ductus Arteriosus After Premature Birth

Keywords

  • Preterm Neonates
  • Patent Ductus Arteriosus
  • Echocardiography
  • Acetaminophen
  • Ibuprofen
03

In context

Ductus Arteriosus, Patent

146 studies on the registry are indexed under Ductus Arteriosus, Patent; 21 are open to participants now.

This study's planned enrollment of 310 is above the median of 80 across 80 interventional studies indexed under Ductus Arteriosus, Patent.

Browse Ductus Arteriosus, Patent studies →

Lead sponsor

Mount Sinai Hospital, Canada is the lead sponsor of 158 studies on the registry; 32 are open to participants now.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
Up to 27 Weeks
Sexes eligible
All
Accepts healthy volunteers
No

Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.

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

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 () > 100 units/L94
  • 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).
Terms in these criteria, in plain language(2)

Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.

ALT and AST (liver enzymes)

Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.

Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.

Platelets

Blood cells that help blood clot. Too few raises the risk of bleeding and bruising. A usual adult range is about 150–400 × 10⁹/L (150,000–400,000 per µL); each lab has its own reference range.

05

Study design

Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Triple (Participant, Investigator, Outcomes assessor)
Enrollment
310 participants (estimated)

Study arms

  • Experimental
    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).

    Drug: Acetaminophen Injection · Drug: Ibuprofen 20 mg/mL oral suspension or Ibuprofen lysine 10 mg/mL injection solution (Neoprofen)

  • Placebo comparator
    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).

    Drug: Ibuprofen 20 mg/mL oral suspension or Ibuprofen lysine 10 mg/mL injection solution (Neoprofen) · Other: Sodium chloride 0.9% injection

Interventions

  • 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

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

    Drug page: Ibuprofen

    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)

  • OtherSodium chloride 0.9% injection

    Placebo- IV q6h for 3 days

06

What researchers measure

Primary outcomes

  1. Composite of pre-discharge mortality or any grade BPD

    Need for oxygen or positive pressure respiratory support at 36 weeks postmenstrual age (PMA)

    Time frame: 36 weeks PMA

Secondary outcomes

  1. PDA treatment success

    Defined as PDA closure or becoming insignificant \[diameter \<1.5 mm\]

    Time frame: 6-10 days post treatment initiation

  2. Renal or hepatic dysfunction

    Renal dysfunction defined as urine output \< 1ml/kg/hour for the previous 24 hours or serum creatinine \> 100 micromol/L; hepatic dysfunction defined as serum aminotransferase (ALT) \> 100 units/L

    Time frame: Occurring within 7 days of treatment initiation

  3. Further exposure to pharmacological PDA treatments

    As per units' standard practice (not part of study procedures)

    Time frame: From date of randomization until death, discharge home or discharge to a community hospital (whichever comes first) assessed up to a maximum of 250 days after randomization

  4. Procedure for PDA closure

    Surgical closure for PDA

    Time frame: From date of randomization until death, discharge home or discharge to a community hospital (whichever comes first) assessed up to a maximum of 250 days after randomization

  5. Mortality

    Death during initial tertiary NICU stay

    Time frame: From date of randomization until date of death (assessed up to a maximum of 250 days after randomization)

  6. Severity of BPD at 36 weeks PDM using Jensen's criteria

    Grade 1, nasal cannula ≤2 L/min; grade 2, nasal cannula \>2 L/min or noninvasive positive airway pressure; grade 3, invasive mechanical ventilation

    Time frame: At 36 weeks PDM

  7. NEC ≥ stage 2A

    NEC ≥ stage 2A during NICU stay

    Time frame: From date of randomization until death, discharge home or discharge to a community hospital (whichever comes first) assessed up to a maximum of 250 days after randomization

  8. Duration (days) of invasive or non-invasive respiratory support

    Days of invasive or non invasive support during NICU say

    Time frame: From date of randomization until death, discharge home or discharge to a community hospital (whichever comes first) assessed up to a maximum of 250 days after randomization

  9. Need for diuretic use

    Diuretic use for BPD treatment

    Time frame: From date of randomization until death, discharge home or discharge to a community hospital (whichever comes first) assessed up to a maximum of 250 days after randomization

  10. Need for systemic steroids

    Use for BPD treatment

    Time frame: From date of randomization until death, discharge home or discharge to a community hospital (whichever comes first) assessed up to a maximum of 250 days after randomization

  11. Sepsis

    Diagnosis of sepsis during NICU stay

    Time frame: From date of randomization until death, discharge home or discharge to a community hospital (whichever comes first) assessed up to a maximum of 250 days after randomization

07

Study locations

6 of 9 sites recruiting
08

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Sep 15, 2026, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
09

Registry details

Key details

Study ID
NCT05340582
Collaborators
Sunnybrook Health Sciences Centre, McMaster Children's Hospital, The Rotunda Hospital, John Hunter Hospital, Royal Alexandra Hospital, Centre de Recheche du Centre Hospitalier Université Laval, Royal North Shore Hospital, Prince of Wales Hospital, Shatin, Hong Kong
Responsible party
Sponsor
First posted
Apr 22, 2022
Start date
Dec 12, 2022
Primary completion
Jan 2027 (estimated)
Completion
Apr 2027 (estimated)
Last update
Sep 15, 2026

Study contacts

Laura Thomas, MSc
Contact
laura.thomas@sinaihealth.ca
416-586-4800 ext. 172060
Amish Jain, MD PhD
principal investigator · MOUNT SINAI HOSPITAL

Oversight

Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

Interested in this study?

Eligibility is decided by the study team. Share this record with your doctor or contact the team directly.

Contact study team

Follow this study

Get an email when the registry record changes — status, dates, results — or when someone posts here.

Sign in to follow

Discussion

Questions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.

Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.

Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.

Studies of the drug tested here: Acetaminophen

Start the discussion