Paracetamol Versus Ibuprofen in Premature Infants With Hemodynamically Significant Patent Ductus Arteriosus (IBUPAR)

Máximo Vento Torres

Status and phase: Unknown; Phase 3

Conditions: Patent Ductus Arteriosus After Premature Birth

Treatments: Drug: Paracetamol; Drug: Ibuprofen

Study type: Interventional

Funder types: Other; NETWORK

Identifiers

NCT04037514

IBUPAR-TRIAL

Details and patient eligibility

About

Multicentric, double-blind clinical trial, which will evaluate the efficacy of iv paracetamol versus standard treatment with ibuprofen in the closure of patent ductus arteriosus in the preterm newborn. Secondarily, we intend to compare the safety of both treatments, increase our knowledge about the pharmacokinetics, pharmacodynamics and pharmacogenetics of paracetamol and ibuprofen in the neonatal period and make a pharmacoeconomic assessment of the use of both drugs.

Full description

Those newborns ≤ 30 weeks of gestational age who are diagnosed in the first 2 weeks of hemodynamically significant ductus arteriosus and who do not meet any exclusion criteria will be eligible to participate in the study.

The PARACETAMOL group will receive intravenous doses of 15 mg/kg administered every 6h for 3 days (up to a maximum of 2 courses, i.e. 6 days). The IBUPROFEN group (control group) will receive the usual treatment, this is an initial dose of 10 mg/kg followed by 5 mg/kg intravenously at 24 and 48 hours after the first (all three doses are considered a treatment course), up a maximum of 2 courses).

A daily echocardiographic control will be performed to evaluate the closure of the ductus. If the ductus remains open and with significant clinical repercussion after completing a 3-day course of treatment, another batch of 3 doses of the same treatment will be administered. If medical treatment fails after two courses (6 days), the possibility of administering a batch of Ibuprofen at usual doses in both groups with the intention of offering standard treatment to all patients will be considered. Once the medical treatment with both drugs is completed if the ductus remains significant, the surgical closure will be carried out.

Enrollment: 300 estimated patients

Sex: All

Ages: Under 14 days old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Written Informed consent of parents/guardians
• Gestacional Age ≤30 weeks
• Postnatal age ≤ 2 weeks
• Need for ventilatory support
• Born in participating hospital/arrival to them within the period of application of the treatment
• 1 st episode of hemodynamically significant Patent Ductus Arteriosus

Exclusion criteria

• Major congenital malformations or chromosomopathies
• Refusal to participate and / or sign the informed consent.
• Impossibility or erroneous randomization
• Participation in another clinical trial with drugs
• Diuresis less than 1 ml / kg / h for 8 h prior to treatment
• Greater than 1.8 mg / dl Creatinine
• Platelets below 50,000 / uL
• Active bleeding (tracheal, gastrointestinal and renal)
• Intraventricular hemorrhage recently (48h) (grades 3-4)
• Severe hyperbilirubinemia
• Liver failure or severe coagulopathy
• Active necrotizing enterocolitis or intestinal perforation
• Septic shock
• Imminent death

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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300 participants in 2 patient groups

Paracetamol

Experimental group

Description:

Intravenous paracetamol 15 mg/kg/6h for 3 or 6 days

Treatment:

Drug: Paracetamol

Ibuprofen

Active Comparator group

Description:

Intravenous ibuprofen 10 mg/kg/24 h (day 1) and 5 mg/kg/24h (day 2 and 3) for 3 or 6 days

Treatment:

Drug: Ibuprofen