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

• Sponsor: Anders Rane, MD, PhD, Senior professor (Other)
• Overall Status: Completed
• CT.gov ID: NCT02079298
• Collaborator: Karolinska University Hospital (Other)
• Enrollment: 80
• Location: 1
• Arms: 4
• Duration (Months): 17
• Patients Per Site Per Month: 4.7

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Ductus Arteriosis, Patent; Bacterial Infections and Mycoses	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.	Phase 4

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 80 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Supportive Care
• 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 Start Date: Apr 1, 2014
• Actual Primary Completion Date: Sep 1, 2015
• Actual Study Completion Date: Sep 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: 1 Premature newborn infants with Gestational Age 23+0 to 26+6 weeks who are treated only with fluconazole.	Drug: Treatment with fluconazole.
Active Comparator: 2 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.
Active Comparator: 3 Premature newborn infants with Gestational Age 27+0 to 36+6 who are treated only with ibuprofen.	Drug: 3. Treatment with ibuprofen.
Placebo Comparator: 4 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.

Outcome Measures

Primary Outcome Measures

1. 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 Outcome Measures

1. 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.

2. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 23 Weeks to 42 Weeks
• Sexes Eligible for Study: All
• Accepts 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.

1. Parents that are in command of the Swedish language and capable of understanding the study plan

2. 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Neonatal Intensive Care Unit, Karolinska University Hopsital	Stockholm		Sweden	171 76

Sponsors and Collaborators

• Anders Rane, MD, PhD, Senior professor
• Karolinska University Hospital

Investigators

• Study Director: Anders Rane, Prof. MD, Karolinska Institutet

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Anders Rane, MD, PhD, Senior professor, Senior professor, Karolinska Institutet
• ClinicalTrials.gov Identifier: NCT02079298
• Other Study ID Numbers: EudraCT number: 2013-003611-21
• First Posted: Mar 5, 2014
• Last Update Posted: Sep 2, 2015
• Last Verified: Sep 1, 2015

• Additional relevant MeSH terms: Mycoses; Bacterial Infections; Bacterial Infections and Mycoses; Fluconazole; Ibuprofen

Study Results

No Results Posted as of Sep 2, 2015