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

Anders Rane, MD, PhD, Senior professor

Status and phase: Completed; Phase 4

Conditions: Bacterial Infections and Mycoses; Ductus Arteriosis, Patent

Treatments: Other: 4. No treatment with either fluconazole nor ibuprofen.; Drug: 3. Treatment with ibuprofen.; Drug: Treatment with fluconazole.; Drug: 2. Treatment with both fluconazole and Ibuprofen.

Study type: Interventional

Funder types: Other

Identifiers

NCT02079298

EudraCT number: 2013-003611-21

Details and patient eligibility

About

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.

Full 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.

Enrollment: 80 patients

Sex: All

Ages: 23 to 42 weeks old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Supportive Care

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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80 participants in 4 patient groups, including a placebo group

1

Active Comparator group

Description:

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

Treatment:

Drug: Treatment with fluconazole.

2

Active Comparator group

Description:

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

Treatment:

Drug: 2. Treatment with both fluconazole and Ibuprofen.

3

Active Comparator group

Description:

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

Treatment:

Drug: 3. Treatment with ibuprofen.

4

Placebo Comparator group

Description:

Premature newborn infants with Gestational Age 27+0 to 36+6 and fullterm infants who are not treated either with fluconazole or ibuprofen.

Treatment:

Other: 4. No treatment with either fluconazole nor ibuprofen.