Paracetamol And Ibuprofen/Indomethacin in Closing Patent Ductus Arteriosus (PAI)

University of Oulu

Status and phase: Terminated; Phase 1

Conditions: Patent Ductus Arteriosus

Treatments: Drug: 0.45% Sodium Chloride; Drug: Indomethacin; Drug: Paracetamol 10Mg/mL; Drug: Ibuprofen

Study type: Interventional

Funder types: Other

Identifiers

NCT03648437

38/2018

Details and patient eligibility

About

The purpose of this pilot trial is to study efficacy and safety of simultaneous intravenous (iv) ibuprofen/indomethacin and paracetamol medications in the closure of patent ductus arteriosus (PDA) in preterm infants. It is randomized, placebo-controlled, double-blind, phase 1, multicenter, clinical trial.

Full description

Premature infants (born before 37 weeks gestational age) with patent ductus arteriosus (PDA) are the focus of the study since no trials on the additive efficacy of these two medications on the contraction of ductus arteriosus are available. Preterm infants who are diagnosed to have a hemodynamically significant PDA and who, according to the decision of the attending clinician, need ibuprofen/indomethacin therapy, are eligible to this trial.

If the parents deny the consent, the patient will be treated according to the standard PDA treatment: three days' iv ibuprofen Pedea® 5mg/ml solution infusion (Oulu, Helsinki, Tartu) dosing: 10mg/kg + 5mg/kg + 5mg/kg (q24h); or three days' iv indomethacin (Turku) 0.2mg/kg + 0.1mg/kg + 0.1mg/kg (q24h). In case of any contraindications for ibuprofen/indomethacin, the treatment would be surgical ligation.

Enrollment: 22 patients

Sex: All

Ages: Under 4 months old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Preterm infants (born before 37+0 gestation weeks) who are diagnosed to have a hemodynamically significant PDA and who, according to the decision of the attending clinician, need ibuprofen therapy, are eligible to this trial.

Exclusion criteria

• severe malformation or suspected chromosomal defect
• other very severe life-threatening disease (e.g. very severe birth asphyxia or persistent pulmonary hypertension, etc.)

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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22 participants in 4 patient groups, including a placebo group

Pedea 5mg/mL and Paracetamol 10mg/mL

Experimental group

Description:

Intravenous (IV) ibuprofen 5mg/mL q 24h for 3 days, dosages: 10mg/kg + 5mg/kg + 5mg/kg and IV paracetamol 10mg/mL for 3 days: loading dose 20mg/kg, following 7.5mg/kg q 6h (up to12 doses)

Treatment:

Drug: Ibuprofen

Drug: Paracetamol 10Mg/mL

Pedea 5mg/mL and 0.45 sodium chloride

Placebo Comparator group

Description:

IV ibuprofen 5mg/mL q 24h for 3 days, dosages: 10mg/kg + 5mg/kg + 5mg/kg and NaCl 0.45% for 3 days, the same amount in mL as would have been given IV paracetamol

Treatment:

Drug: Ibuprofen

Drug: 0.45% Sodium Chloride

Indomethacin 25mg/mL and Paracetamol10mg/mL

Experimental group

Description:

Intravenous (IV) indometahcin 25mg/mL q 24h for 3 days, dosages: 0.2mg/kg + 0.1mg/kg + 0.1mg/kg and IV paracetamol 10mg/mL for 3 days: loading dose 20mg/kg, following 7.5mg/kg q 6h (up to12 doses)

Treatment:

Drug: Paracetamol 10Mg/mL

Drug: Indomethacin

Indomethacin 25mg/mL and 0.45 sodium chloride

Placebo Comparator group

Description:

Intravenous (IV) indomethacin 25mg/mL q 24h for 3 days, dosages: 0.2mg/kg + 0.1mg/kg + 0.1mg/kg and NaCl 0.45% for 3 days, the same amount in mL as would have been given IV paracetamol

Treatment:

Drug: Indomethacin

Drug: 0.45% Sodium Chloride