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

Oral Nystatin Prophylaxis to Prevent Systemic Fungal Infection in Very Low Birth Weight Preterm Infants: a Randomized Controlled Trial

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.

Study Overview

• Status: Completed
• Conditions: Fungal Infections Systemic
• Intervention / Treatment: Drug: Nystatin Oral

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 Type: Interventional
• Enrollment (Actual): 95
• Phase: Phase 4

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 3 days (CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: PREVENTION
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Nystatin group; Nystatin oral 1 mL (0.5 mL coated in oral cavity and the rest was given through orogastric tube) three times a day	Drug: Nystatin Oral; Nystatin oral suspension; Other Names: Mycostatin
NO_INTERVENTION: Control group; Sterile water 1 mL three times a day for oral hygiene

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Fungal colonization	Weekly oropharyngeal and rectal fungal surveillance results are evaluated. Colonization is considered positive if yeast cells were found on either oral or rectal specimen	1 to 6 weeks
Systemic fungal infection	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)	1 to 6 weeks

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Dr Cipto Mangunkusumo General Hospital
• Investigators: Principal Investigator: Lily Rundjan, MD, Dr Cipto Mangunkusumo General Hospital

Publications and helpful links

General Publications

• Rundjan L, Wahyuningsih R, Oeswadi CA, Marsogi M, Purnamasari A. Oral nystatin prophylaxis to prevent systemic fungal infection in very low birth weight preterm infants: a randomized controlled trial. BMC Pediatr. 2020 Apr 17;20(1):170. doi: 10.1186/s12887-020-02074-0.

Study record dates

Study Major Dates

• Study Start (ACTUAL): October 1, 2010
• Primary Completion (ACTUAL): November 1, 2012
• Study Completion (ACTUAL): January 1, 2013

Study Registration Dates

• First Submitted: December 27, 2017
• First Submitted That Met QC Criteria: December 27, 2017
• First Posted (ACTUAL): January 4, 2018

Study Record Updates

• Last Update Posted (ACTUAL): January 4, 2018
• Last Update Submitted That Met QC Criteria: December 27, 2017
• Last Verified: December 1, 2017

More Information

Terms related to this study

• Keywords: Nystatin; Fungal colonization; Systemic fungal infections
• Additional Relevant MeSH Terms: Pathologic Processes; Systemic Inflammatory Response Syndrome; Inflammation; Disease Attributes; Body Weight; Bacterial Infections and Mycoses; Sepsis; Infections; Communicable Diseases; Mycoses; Birth Weight; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Anti-Bacterial Agents; Membrane Transport Modulators; Antifungal Agents; Ionophores; Nystatin
• Other Study ID Numbers: 434/PT02.FK/ETIK/2010

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No