Bacterial Infections and Mycoses, Ductus Arteriosis, Patent
Conditions
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.
Interventions
DRUGTreatment with fluconazole.
DRUG2. Treatment with both fluconazole and Ibuprofen.
DRUG3. Treatment with ibuprofen.
OTHER4. No treatment with either fluconazole nor ibuprofen.
Sponsors
Karolinska University Hospital
Anders Rane, MD, PhD, Senior professor
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
SUPPORTIVE_CARE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
23 Weeks to 42 Weeks
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Urinary concentrations of prostacycline (PGI2) and thromboxane A2 (TxA2) measured in picogram/milliliter. | 5 days | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Concentration of thromboxane A2 (TXA2) and prostacycline (PGI2) in relation to genetic variation of the enzymes of the Cytochrome (P4502C) family. | 5 days | 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. |
| Number of and type of Adverse Drug Reactions | 5 days | To evaluate safety of fluconazole and ibuprofen given separately or in combination to newborn infants with clinical indication for treatment with these drugs. |
Countries
Sweden
Outcome results
None listed