Patent Ductus Arteriosus After Premature BirthPhase 2NCT05340582
Co-administration of Acetaminophen With Ibuprofen to Improve Duct-Related Outcomes in Extremely Premature Infants
A Phase 2 study testing Acetaminophen Injection, Ibuprofen 20 mg/mL oral suspension or Ibuprofen lysine 10 mg/mL injection solution (Neoprofen) and Sodium chloride 0.9% injection in people with Patent Ductus Arteriosus After Premature Birth, run by Mount Sinai Hospital, Canada at 9 sites in 4 countries.
Trial 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). Read more about this study
- Who is it for?
- Ages Up to 27 weeks
- Conditions the study is for
- Patent Ductus Arteriosus After Premature Birth
- What is being tested?
- Acetaminophen Injection, Ibuprofen 20 mg/mL oral suspension or Ibuprofen lysine 10 mg/mL injection solution (Neoprofen) and Sodium chloride 0.9% injection
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 310 participants
- Where
- 9 sitesin 4 countries
- Study dates
- 12 Dec 2022to Apr 2027
- Phase
- Phase 2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Up to 27 weeks
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 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.
Who cannot join
- 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).
Trial locations and contacts
9 sites in 4 countries. Contact the study team or a site near you to ask about taking part.
9 sites in 4 countries
Canada5 sites, 5 recruiting
- Recruiting
Royal Alexandra Hospital
Edmonton, Ontario, T5H 3V9
Dr. Georg Schmölzer, MD, PHD
- Recruiting
McMaster Children's Hospital
Hamilton, Ontario, L8N 3Z5
Amneet Sidhu, MD
- Recruiting
Centre Hospitalier de l'Université Laval
Québec, Quebec, G1V 4G2
Dr. Audrey Hébert, MD
- Recruiting
Sunnybrook Health Sciences Centre
Toronto, Ontario, M4N 3M5
Dany Weisz, MD, MSc
Dany Weisz, MD, MSc
- Recruiting
Mount Sinai Hospital
Toronto, Ontario, M5G 1X5
Amish Jain, MD PhD
Australia2 sites, 1 recruiting
- Active, not recruiting
John Hunter Hospital
Newcastle, New South Wales, 2300
- Recruiting
Royal North Shore Hospital
St Leonards, New South Wales, 2065
Dr. Amber Siegel, MD
Hong Kong1 site, 1 recruiting
- Not yet recruiting
Prince of Wales Hospital
Shatin, NT
Dr. Genevieve Fung, MD
About this study
Official title: Co-administration of Acetaminophen With Ibuprofen to Improve Duct-Related Outcomes in Extremely Premature Infants - The ACEDUCT Trial
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.
- Being tested
- Acetaminophen Injection, Ibuprofen 20 mg/mL oral suspension or Ibuprofen lysine 10 mg/mL injection solution (Neoprofen), Sodium chloride 0.9% injection
- Keywords
- Preterm Neonates, Patent Ductus Arteriosus, Echocardiography, Acetaminophen, Ibuprofen
- Medical subject headings
- Ductus Arteriosus, Patent
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Acetaminophen InjectionDrug
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)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% injectionOther
Placebo- IV q6h for 3 days
| Study group | Role | What they receive |
|---|---|---|
| Combination Therapy | Experimental | 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). Receives: Drug: Acetaminophen Injection; Drug: Ibuprofen 20 mg/mL oral suspension or Ibuprofen lysine 10 mg/mL injection solution (Neoprofen) |
| Standard Clinical Practice - Monotherapy | Placebo comparator | 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). Receives: Drug: Ibuprofen 20 mg/mL oral suspension or Ibuprofen lysine 10 mg/mL injection solution (Neoprofen); Other: Sodium chloride 0.9% injection |
What is being measured
The primary outcome is the main question the study is designed to answer.
Composite of pre-discharge mortality or any grade BPD
Need for oxygen or positive pressure respiratory support at 36 weeks postmenstrual age (PMA)
Measured: 36 weeks PMA
Secondary outcomes (11)
PDA treatment success
Defined as PDA closure or becoming insignificant [diameter <1.5 mm]
Measured: 6-10 days post treatment initiation
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
Measured: Occurring within 7 days of treatment initiation
Further exposure to pharmacological PDA treatments
As per units' standard practice (not part of study procedures)
Measured: 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
Procedure for PDA closure
Surgical closure for PDA
Measured: 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
Mortality
Death during initial tertiary NICU stay
Measured: From date of randomization until date of death (assessed up to a maximum of 250 days after randomization)
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
Measured: At 36 weeks PDM
NEC ≥ stage 2A
NEC ≥ stage 2A during NICU stay
Measured: 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
Duration (days) of invasive or non-invasive respiratory support
Days of invasive or non invasive support during NICU say
Measured: 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
Need for diuretic use
Diuretic use for BPD treatment
Measured: 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
Need for systemic steroids
Use for BPD treatment
Measured: 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
Sepsis
Diagnosis of sepsis during NICU stay
Measured: 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
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Apr 2022
- Study start12 Dec 2022
- Primary completionJan 2027 (estimated)
- Study completionApr 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Patent Ductus Arteriosus After Premature BirthStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- 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
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 310 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Mount Sinai Hospital, Canada
- Sponsor type
- University, hospital or other
- 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
- Investigators
- Amish Jain, MD PhD, Principal investigator, MOUNT SINAI HOSPITAL
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05340582
- Sponsor's protocol ID
- CTO 1875
- Status last verified
- Aug 2026
- First submitted
- 16 Mar 2022
- Last updated
- 15 Sep 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No