Safety of Fluconazole Treatment of Premature and Full-term Newborn Infants

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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Ductus Arteriosis, Patent, Bacterial Infections and Mycoses

Intervention / Treatment
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* Drug: Treatment with fluconazole.
* Drug: 2. Treatment with both fluconazole and Ibuprofen.
* Drug: 3. Treatment with ibuprofen.
* Other: 4. No treatment with either fluconazole nor ibuprofen.


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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. Parents that are in command of the Swedish language and capable of understanding the study plan Informed written parental consent Exclusion Criteria: 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. Infants without possibility to conceive the objectives and implications of the study in the opinion of the investigator.

Ages Eligible for Study
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Minimum Age: 23 Weeks
Maximum Age: 42 Weeks

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 1<br>Premature newborn infants with Gestational Age 23+0 to 26+6 weeks who are treated only with fluconazole. | Drug: Treatment with fluconazole.<br> <br> |
| Active Comparator: 2<br>Premature newborn infants with Gestational Age 23+0 to 26+6 weeks who are treated with both fluconazole and Ibuprofen. | Drug: 2. Treatment with both fluconazole and Ibuprofen.<br> <br> |
| Active Comparator: 3<br>Premature newborn infants with Gestational Age 27+0 to 36+6 who are treated only with ibuprofen. | Drug: 3. Treatment with ibuprofen.<br> <br> |
| Placebo Comparator: 4<br>Premature newborn infants with Gestational Age 27+0 to 36+6 and fullterm infants who are not treated either with fluconazole or ibuprofen. | Other: 4. No treatment with either fluconazole nor ibuprofen.<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Urinary concentrations of prostacycline (PGI2) and thromboxane A2 (TxA2) measured in picogram/milliliter. | 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 for fungal infection prophylaxis and/or patent ductus arteriosis (PDA), respectively. | 5 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Concentration of thromboxane A2 (TXA2) and prostacycline (PGI2) in relation to genetic variation of the enzymes of the Cytochrome (P4502C) family. | To evaluate if genetic variability in the enzyme Cytochrome (P4502C) influence the urinary excretion of two vasoactive arachidonic acid products: thromboxane A2 (TXA2) and prostacycline (PGI2) in newborn infants treated with fluconazole and/or ibuprofen. | 5 days | 
| Number of and type of Adverse Drug Reactions | To evaluate safety of fluconazole and ibuprofen given separately or in combination to newborn infants with clinical indication for treatment with these drugs. | 5 days |