Clinical trial NCT02079298: Safety of Fluconazole Treatment of Premature and Full-term Newborn Infants
Official title: Safety of Fluconazole Treatment of Premature and Full-term Newborn Infants - A Study on Interactions by Nonsteroidal Anti Inflammatory Drugs (NSAIDs) With Fluconazole in Respect of Pharmacodynamic Endpoints With Urinary Excretion of Vasoactive Endobiotics
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Ductus Arteriosis, Patent
Bacterial Infections and Mycoses
Lead sponsor: Karolinska Institutet
Sponsor class: OTHER
Collaborators: name: Karolinska University Hospital
First posted: 2014-03-05
Enrollment: 80
Sex: ALL
Minimum age (years): 23
Maximum age (years): 42
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SUPPORTIVE_CARE

Brief summary: This study will investigate pharmacological interventions between fluconazole and ibuprofen when they are given to premature newborn babys. This in order to find out if the drugs are influencing each other when they are given at the same time. The study is meant to find out if there are reasons to adjust the dose when fluconazole and ibuprofen are given together.

Detailed description: To evaluate the effect of fluconazole and/or ibuprofen on the urinary excretion of two vasoactive arachidonic acid products, thromboxane A2 (TXA2) and prostacycline (PGI2), in newborn infants treated with one or both of these drugs because of fungal infection prophylaxis and/or patent ductus arteriosis (PDA), respectively, as measurement of the possible interactions between these drugs.

Eligibility criteria: Inclusion Criteria:

1. Newborn infants in need of prophylaxis with fluconazole according to clinical routines and/or clinical indication for treatment of Patent Ductus Arteriosis (PDA), or newborn infants who are not treated with either fluconazole or ibuprofen according to the following study groups:

   1.1 Premature newborn infants with Gestational Age 23+0 to 26+6 weeks who are treated only with fluconazole.

   1.2 Premature newborn infants with Gestational Age 23+0 to 26+6 weeks who are treated with both fluconazole and Ibuprofen.

   1.3 Premature newborn infants with Gestational Age 27+0 to 36+6 who are treated only with ibuprofen.

   1.4 Premature newborn infants with Gestational Age 27+0 to 36+6 and fullterm infants who are not treated either with fluconazole or ibuprofen.
2. Parents that are in command of the Swedish language and capable of understanding the study plan
3. Informed written parental consent

Exclusion Criteria:

1. Infants who need treatment with other drugs that are metabolised by enzyme Cytochrome (CYP2C9) (such as phenytoin, sulphamethoxazole, fluvastatin, sildenafil, losartan, irbesartan, torsemide, tienilic acid), or any other enzyme involved in the metabolism of fluconazole and or NSAIDs, or treatment with drugs that interact with NSAIDs at the cyclooxygenase level, or interact with the vasal effects of the metabolic products of the cyclooxygenase.
2. Infants without possibility to conceive the objectives and implications of the study in the opinion of the investigator.

Primary outcomes:
measure: Urinary concentrations of prostacycline (PGI2) and thromboxane A2 (TxA2) measured in picogram/milliliter.
timeFrame: 5 days
Secondary outcomes:
measure: Concentration of thromboxane A2 (TXA2) and prostacycline (PGI2) in relation to genetic variation of the enzymes of the Cytochrome (P4502C) family.
timeFrame: 5 days
measure: Number of and type of Adverse Drug Reactions
timeFrame: 5 days
Other outcomes:
Locations:
city: Stockholm
country: Sweden
facility: Neonatal Intensive Care Unit, Karolinska University Hopsital
Study officials:
affiliation: Karolinska Institutet
name: Anders Rane, Prof. MD
role: STUDY_DIRECTOR
References: