Safety and Efficacy of Mupirocin in Eradicating Colonization With S. Aureus in Critically Ill Infants

NCT01827358 | Completed Phase 2 Results FDA Drug

• 1 other identifier: 09-0065
• Study Type: interventional
• Target: 155
• Locations: 1 country
• Sites: 6

Brief Summary

The objective of this trial is 1) to evaluate the safety and clinical acceptability of a 5-day course of mupirocin applied every 8 hours (± 2 hours) to the nares, umbilical and perianal areas of infants residing in the ICU. 2) to examine the efficacy of mupirocin in eradicating SA colonization of infants in the ICU, defined as the absence of SA in cultures of the nares, umbilical, and perianal areas on day 8 (± 2) (primary decolonization) 3) to examine the efficacy of mupirocin in achieving persistent eradication of SA colonization among infants residing in the ICU,defined as the absence of SA in cultures of the nares, umbilical, and perianal areas. Duration is 36 months. Enrolled infants will continue to receive medical care as they otherwise would if they were not enrolled in the trial. The study will be powered with a primary endpoint with 126 participants. Enrollment may continue to 500 participants to power secondary and exploratory endpoints and assist design subsequent studies.

Conditions

Staphylococcal Infection

Keywords

antibacterial agent; children; colonisation; critically ill; infants; mupirocin; prevention; Staphylococcus aureus

Outcome Measures

Primary Outcomes (5)

• Number of Participants With Solicited Adverse Events (AEs) During Days 1-7

  Participants were evaluated for solicited adverse events while in the NICU/ICU on days 1-7. Participants were counted if they experienced the symptom at any severity during the reporting period. Although participants received only 5 days of mupirocin, solicited events were collected through day 7.

  Days 1 through 7

• Number of Participants With Moderate and Severe Unsolicited Adverse Events; During Days 1-7

  Participants were evaluated for moderate and severe unsolicited adverse events (that were not otherwise considered pre-defined trial endpoints) while in the NICU/ICU on days 1-7. Although participants received 5 days of mupirocin, unsolicited events were collected until day 7. Moderate events were defined as those that may cause some interference with functioning and daily activities. Severe events were defined as those that interrupt the participant's usual daily activities and may require systemic drug therapy or other treatment. Severe events were usually incapacitating.

  Days 1 through 7

• Number of Participants With Serious Adverse Events (SAEs) During Days 1-7

  Participants were evaluated for Serious Adverse Events (SAEs) while in the NICU/ICU on days 1-7. Although participants received only 5 days of mupirocin, SAEs were collected through day 7. An adverse event or suspected adverse reaction was considered serious if, in the view of either the investigator or sponsor, it resulted in any of the following outcomes: death; a life-threatening adverse event (an event that places the participant at immediate risk of death; it doesn't include an adverse event, had it occurred in a more severe form, might have caused death); inpatient hospitalization or prolongation of existing hospitalization; a persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions; or any other event that when based upon appropriate medical judgement may have jeopardized the participant and may have required medical or surgical intervention to prevent one of the outcomes listed in this definition.

  Days 1 through 7

• Primary Decolonization Efficacy- Number of Participants in the Treatment and Control Groups Who Have no Detectable S. Aureus (SA) on Direct Nasal, Umbilical, and Perianal (NUP) Cultures Obtained on Day 8.

  Colonization was defined as the presence of SA identified by NUP culture without signs of illness or infection. On day 8, participants were swabbed in each of three areas: nasal, umbilical, and perianal. These swabs were cultured by direct plating. If SA did not grow on any of these cultures the infant was considered to be decolonized. If SA grew on any one of these cultures the infant was considered to be colonized with SA.

  Day 8

• Persistent Decolonization Efficacy- Number of Participants in the Treatment and Control Groups Who Have no Detectable S. Aureus (SA) on Direct Nasal, Umbilical, and Perianal (NUP) Cultures on Days 8 and 22.

  Participants were admitted into the study based on being colonized with SA. Participants who were decolonized both on day 8 and day 22, as determined by NUP cultures were considered to have persistent decolonization. Colonization was defined as the presence of SA identified by NUP culture without signs of illness or infection. NUP swabs were collected on day 8 and on day 22 and cultured by direct plating. If the cultures were negative for SA at both day 8 and day 22 the participant was considered to have persistent decolonization. Colonization with SA was a prerequisite for enrollment, because of this there was no baseline measure.

  Day 8 and Day 22

Secondary Outcomes (9)

• Relative Risk of Occurrence of Non-SA Clinical Infection in the Treatment Compared to Control Group in the Intent To Treat Cohort

  Day 1 through 85

• Relative Risk of Occurrence of Non-SA Clinical Infection in the Treatment Compared to Control Group in the According to Protocol Cohort.

  Day 1 through 85

• Median Time to Occurrence of Severe (Stage II-III) Necrotizing Enterocolitis (NEC) in the Treatment Compared to Control Group.

  Day 1 through 85

• Protective Efficacy of Clinical S. Aureus (SA) Infection in the Treatment Compared to the Control Group During Days 1-22 or Until Discharge, Whichever Occurs First, Using the Intent to Treat Cohort.

  Day 1 through 22

• Protective Efficacy of Clinical SA Infection in the Treatment Compared to the Control Group During Days 1-22 or Until Discharge, Whichever Occurs First, Using the According to Protocol (ATP) Cohort.

  Day 1 through 22

Study Arms (2)

Group 1

EXPERIMENTAL

Subjects receive a 5-day course of mupirocin calcium ointment 2 % 20 mg intranasally applied every 8 hours and a topical skin application (umbilical and perianal area) of mupirocin calcium cream 2% 20 mg applied every 8 hours for a total of 15 doses

Drug: Mupirocin calcium

Group 2

NO INTERVENTION

No treatment

Interventions

Mupirocin calcium DRUG

Mupirocin calcium cream 2% applied topically to umbilicus and perianal area every 8 hours for 5 days, for a total of 15 applications

Group 1

Eligibility Criteria

• Age: Up to 24 Months
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• \. Currently admitted to a NICU or ICU at a participating site 2. Chronological age less than 24 months 3. Evidence of colonization with SA (MRSA or MSSA) based on a positive nasal surveillance culture. Randomization must occur within 7 days (168 hours) of when the site's laboratory reports the first SA positive nasal surveillance swab 4. The attending neonatologist/ intensivist anticipates that the infant will remain in the ICU for a minimum of 14 days after enrollment 5. Parent or legal guardian agrees that the infant will not participate in a research trial involving the administration of an investigational drug for 14 days following enrollment

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (6)

Emory University Hospital Midtown - Neonatal Intensive Care Unit

Atlanta, Georgia, 30308-2208, United States

Location

University of Maryland Medical Center - Children's Hospital - Neonatal Intensive Care Unit

Baltimore, Maryland, 21201-1595, United States

Location

Children's Mercy Hospital and Clinics - Infectious Diseases

Kansas City, Missouri, 64108-4619, United States

Location

Saint Louis University School of Medicine - Cardinal Glennon Children's Medical Center - NICU

St Louis, Missouri, 63104-1003, United States

Location

Cincinnati Children's Hospital Medical Center - Infectious Diseases

Cincinnati, Ohio, 45229-3039, United States

Location

Vanderbilt University - Pediatric - Vanderbilt Vaccine Research Center

Nashville, Tennessee, 37232-2573, United States

Location

Related Publications (1)

• Kotloff KL, Shirley DT, Creech CB, Frey SE, Harrison CJ, Staat M, Anderson EJ, Dulkerian S, Thomsen IP, Al-Hosni M, Pahud BA, Bernstein DI, Yi J, Petrikin JE, Haberman B, Stephens K, Stephens I, Oler RE Jr, Conrad TM. Mupirocin for Staphylococcus aureus Decolonization of Infants in Neonatal Intensive Care Units. Pediatrics. 2019 Jan;143(1):e20181565. doi: 10.1542/peds.2018-1565.

  PMID: 30587533 DERIVED

MeSH Terms

Conditions

Staphylococcal Infections; Critical Illness

Interventions

Mupirocin

Condition Hierarchy (Ancestors)

Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Epoxy Compounds; Ethers, Cyclic; Ethers; Organic Chemicals; Pyrans; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fatty Acids; Lipids

Results Point of Contact

• Title: Karen Kotloff, MD
• Organization: University of Maryland Medical Center

kkotloff@medicine.umaryland.edu

410-706-5328

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 4, 2013
• First Posted: April 9, 2013
• Study Start: April 30, 2014
• Primary Completion: June 7, 2016
• Study Completion: June 21, 2016
• Last Updated: July 7, 2017
• Results First Posted: July 7, 2017

Record last verified: 2016-04-13

Locations

US (6)