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

Last updated: February 10, 2025
Sponsor: Mount Sinai Hospital, Canada
Overall Status: Active - Recruiting

Phase

2

Condition

N/A

Treatment

Sodium chloride 0.9% injection

Acetaminophen Injection

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

Clinical Study ID

NCT05340582
CTO 1875
  • Ages < 27
  • All Genders

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).

Eligibility Criteria

Inclusion

Inclusion Criteria:

  • Preterm infants born <27+0 weeks gestational age

  • Permission given by the attending clinician to approach and then consent obtainedfrom parents

  • Diagnosis of PDA ≥ 1.5 mm on echocardiography with unrestrictive predominantly leftto right shunt

  • Designated to receive first treatment course with intravenous or enteral ibuprofen,as decided by the attending team.

Exclusion

Exclusion Criteria:

  • Chromosomal anomaly

  • Pre-treatment renal dysfunction defined as urine output < 1ml/kg/hour for theprevious 24 hours or serum creatinine > 100 micromol/L

  • Pre-treatment hepatic dysfunction defined as serum aminotransferase (ALT) > 100units/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 indomethacinuse for prevention of intraventricular hemorrhage will not be considered as PDAtreatment).

Study Design

Total Participants: 310
Treatment Group(s): 3
Primary Treatment: Sodium chloride 0.9% injection
Phase: 2
Study Start date:
December 12, 2022
Estimated Completion Date:
April 30, 2027

Connect with a study center

  • John Hunter Hospital

    Newcastle, New South Wales 2300
    Australia

    Site Not Available

  • Royal North Shore Hospital

    St Leonards, New South Wales 2065
    Australia

    Site Not Available

  • Royal Alexandra Hospital

    Edmonton, Ontario T5H 3V9
    Canada

    Site Not Available

  • McMaster Children's Hospital

    Hamilton, Ontario L8N 3Z5
    Canada

    Active - Recruiting

  • Mount Sinai Hospital

    Toronto, Ontario M5G 1X5
    Canada

    Active - Recruiting

  • Sunnybrook Health Sciences Centre

    Toronto, Ontario M4N 3M5
    Canada

    Active - Recruiting

  • Centre Hospitalier de l'Université Laval

    Quebec, G1V 4G2
    Canada

    Site Not Available

  • Prince of Wales Hospital

    Shatin, NT
    Hong Kong

    Site Not Available

  • The Rotunda Hospital

    Dublin,
    Ireland

    Active - Recruiting

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