Oral Nystatin Prophylaxis to Prevent Systemic Fungal Infection in Very Low Birth Weight Preterm Infants

Phase 4

Completed

• Conditions: Fungal Infections Systemic
• Interventions: Drug: Nystatin Oral

• Registration Number: NCT03390374
• Lead Sponsor: Dr Cipto Mangunkusumo General Hospital

Brief Summary

This study determines the effectiveness of oral nystatin as prophylaxis in order to prevent systemic fungal infection in very low birth weight preterm neonates. 47 participants received oral nystatin and 48 participants received sterile water as part of oral hygiene.

Detailed Description

Oral nystatin is an effective and safe alternative fungal prophylaxis. Some previous studies (1 randomized controlled trial and 4 observational studies) showed that oral nystatin prophylaxis reduce fungal colonization and decrease risk of systemic fungal infection in very low birth weight infants.

Nystatin is a non-absorbable antifungal agent with minimal side effects that works by binding on the major component of fungus cell membrane and causes death of the fungus. Its efficacy as fungal prophylaxis is comparable with Fluconazole but does not linked to drug-induced liver injury.

To determine this effectivity, we recruit eligible neonates who are admitted in our neonatal intensive care unit and randomly assign them into 2 groups once noted written parental consent. One group is given nystatin via oral and/or orogastric tube and the other group only receives sterile water as part of oral hygiene. Weekly fungal surveillance cultures (oropharyngeal and rectal) are done to evaluate colonization. Further examinations (blood/cerebrospinal fluid/deep tissue/urine culture) are done once noted clinical signs of systemic fungal infections.

Data analysis is conducted with intent-to treat approach. Significance testing is done by chi-square or fisher's exact test as needed.

Study Timeline

• Study Start: 2010-10
• Primary Completion: 2012-11
• Study Completion: 2013-01
• Status Verified: 2017-12
• Study First Submitted: 2017-12-27
• Study First Submitted QC: 2017-12-27
• Last Update Submitted: 2017-12-27
• Study First Posted: 2018-01-04
• Last Update Posted: 2018-01-04

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 95

Inclusion Criteria

• Gestational age <= 32 weeks and/or birth weight <=1500 grams
• 1 or more systemic fungal infection risk factors (antibiotic therapy, intravenous access, endotracheal tube, orogastric tube, urinary catheter, corticosteroid therapy, parenteral nutrition, theophylline therapy)

Exclusion Criteria

• Suspected of having necrotizing enterocolitis within 72 hours after birth, cyanotic congenital heart disease, chromosomal defects, or critical conditions whom were not expected to live more than 72 hours after birth

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Nystatin group	Nystatin Oral	Nystatin oral 1 mL (0.5 mL coated in oral cavity and the rest was given through orogastric tube) three times a day

Primary Outcome Measures

Name	Time	Method
Systemic fungal infection	1 to 6 weeks	Culture of blood, cerebrospinal fluid, deep tissue, or urine is evaluated in participants with symptoms/signs of systemic infection. Proven systemic fungal infection is defined as a positive blood, cerebrospinal fluid, deep tissue, or urine culture (\> 10.000 or more colony forming unit/mL from sterile bladder catheterization or suprapubic aspiration)
Fungal colonization	1 to 6 weeks	Weekly oropharyngeal and rectal fungal surveillance results are evaluated. Colonization is considered positive if yeast cells were found on either oral or rectal specimen

Secondary Outcome Measures

Name	Time	Method
Mortality rates	1 to 6 weeks	Fungal and overall related mortality rates
Nystatin-related adverse drug reactions	1 to 6 weeks	Any side effects of nystatin as reported in references