Recruiting
Phase 2

Acetaminophen & Ibuprofen

Sponsor:

Mount Sinai Hospital, Canada

Code:

NCT05340582

Conditions

Patent Ductus Arteriosus After Premature Birth

Eligibility Criteria

Sex: All

Age: 0

Healthy Volunteers: Not accepted

Interventions

Acetaminophen Injection

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

Sodium chloride 0.9% injection

Study Details

Brief 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.

Conditions

Patent Ductus Arteriosus After Premature Birth

Study ID

NCT05340582

Start date

Dec 12, 2022

Status verified date

Feb, 2026

Completion date

Apr, 2027

Anticipated

Primary completion date

Jan, 2027

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 0

Healthy Volunteers: Not accepted

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).

Study Design

Enrollment

310 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

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).

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).

Interventions

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

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)

Sodium chloride 0.9% injection

Placebo- IV q6h for 3 days

Primary outcome measure

  • Composite of pre-discharge mortality or any grade BPD [ Time Frame: 36 weeks PMA ]

Central Contacts and Locations

Central contacts

Laura Thomas, MSc

416-586-4800laura.thomas@sinaihealth.ca

Locations

Royal Alexandra Hospital

Recruiting

Edmonton, Ontario, Canada, T5H 3V9

Principal Investigator:

Dr. Georg Schmölzer, MD, PHD

McMaster Children's Hospital

Recruiting

Hamilton, Ontario, Canada, L8N 3Z5

Principal Investigator:

Amneet Sidhu, MD

Sunnybrook Health Sciences Centre

Recruiting

Toronto, Ontario, Canada, M4N 3M5

Principal Investigator:

Dany Weisz, MD, MSc

Mount Sinai Hospital

Recruiting

Toronto, Ontario, Canada, M5G 1X5

Principal Investigator:

Amish Jain, MD PhD

More Information

Sponsor

Mount Sinai Hospital, Canada

Last update posted

Apr 6, 2026

Last verified

Feb, 2026

Keywords

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

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-10. This information was provided to ClinicalTrials.gov by Mount Sinai Hospital, Canada on 2026-04-06.