Efficacy of Prophylactic Fluconazole Therapy in Preterm and Very Low Birth Weight Neonates in Preventing Invasive Fungal Infection.

Invasive fungal infection is detecting candida species in blood, cerebrospinal fluid, or urine. Clinical signs of invasive candidiasis may include lethargy, temperature instability, feeding intolerance, apnea, hypotension, respiratory distress, abdominal distension, and thrombocytopenia. Fungal infection has been associated with an increased risk of retinopathy of prematurity and chronic lung disease. Preterm and low birth weight infants have an immature immune system that predisposes them to infections with bacteria, viruses, and fungi. These infants usually require prolonged admission in the neonatal unit and there is often a need for the administration of broad-spectrum antibiotics which predisposes them to colonization with fungi that may invade to cause systemic disease8. Other risk factors for the development of invasive fungal infection include endotracheal intubation, abdominal surgery, the presence of a central venous catheter, administration of H2 antagonists, and steroids. Infection with Candida species is the third most common cause of bloodstream infection in premature infants. Mortality in preterm infants due to invasive candidiasis is around 20% and can be as high as 50% in infants weighing <1500g at birth. Invasive candidiasis is the second most common infectious cause of death in extremely preterm infants. The present study was conducted to determine the incidence of invasive candidiasis among preterm and very low birth weight infants in our neonatal unit and to evaluate the efficacy of prophylactic fluconazole in preventing invasive fungal infection. Based on the results of the present study institutional guidelines may be designed in our neonatal unit relating to antifungal prophylaxis in preterm and very low birth weight infants.

Study Overview

• Status: Completed
• Conditions: Invasive Candidiases
• Intervention / Treatment: Drug: Fluconazole; Drug: Saline

• Study Type: Interventional
• Enrollment (Actual): 110
• Phase: Phase 3

Contacts and Locations

Study Locations

• Pakistan
  • Punjab
    • Lahore, Punjab, Pakistan
      • Services Hospital Lahore

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Preterm babies born less than 34 weeks of gestation
• very low birth weight babies (weighing < 1500 g at birth)
• Babies <72 hours of age

Exclusion Criteria:

• Babies >72 hours of life
• Syndromic babies
• Babies with suspected metabolic disorders

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Prophylactic Fluconazole; 12 mg/Kg loading dose of fluconazole given intravenously followed by 6 mg/Kg every 48 hours till 14 days of life, and then 6 mg/kg/day thereafter, for a total duration of 6 weeks (42 days).	Drug: Fluconazole; Fluconazole will be given for prevention of invasive candidiasis in preterm and very low birthweight babies.
Placebo Comparator: placebo group; Normal Saline 2cc given intravenously	Drug: Saline; 0.9% Saline 2cc intravenous will be given to preterm babies in placebo group.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Invasive candidiases	Positive blood, cerebrospinal fluid, or urine culture for candida species will be regarded as invasive candidiasis.	2 weeks

Collaborators and Investigators

• Sponsor: Services Institute of Medical Sciences, Pakistan
• Investigators: Principal Investigator: M Tauseef Omer, MBBS FCPS Pediatrics, Services Hospital, Lahore

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2021
• Primary Completion (Actual): October 31, 2021
• Study Completion (Actual): October 31, 2021

Study Registration Dates

• First Submitted: April 27, 2023
• First Submitted That Met QC Criteria: April 27, 2023
• First Posted (Actual): May 8, 2023

Study Record Updates

• Last Update Posted (Actual): May 8, 2023
• Last Update Submitted That Met QC Criteria: April 27, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; Body Weight; Bacterial Infections and Mycoses; Candidiasis; Candidiasis, Invasive; Mycoses; Birth Weight; Invasive Fungal Infections; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Hormones, Hormone Substitutes, and Hormone Antagonists; Cytochrome P-450 Enzyme Inhibitors; Hormone Antagonists; Antifungal Agents; Steroid Synthesis Inhibitors; 14-alpha Demethylase Inhibitors; Cytochrome P-450 CYP2C9 Inhibitors; Cytochrome P-450 CYP2C19 Inhibitors; Fluconazole
• Other Study ID Numbers: FluconazolePreterm1

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes