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

NCT ID: NCT01827358

Last Updated: 2017-07-07

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 155 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-04-30
• Study Completion Date: 2016-06-21

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.

Detailed Description

This is a Phase 2, open label, multi-center, randomized trial to determine the safety and efficacy of mupirocin in eradicating colonization with Staphylococcus aureus (SA) and preventing the occurrence of invasive and other clinically significant SA infections among critically ill infants in the ICU. Infants hospitalized in an ICU at any one of the 6 participating centers with a positive nasal culture for SA will be eligible to enroll. Infants will be stratified by birth gestational age (< 28 weeks and <8 weeks of post-natal life or > /= 28 weeks / < 28 weeks and > /=8 weeks of post-natal life) and colonizing strain methicillin-resistant Staphylococcus aureus (MRSA) or methicillin-sensitive Staphylococcus aureus (MSSA) and then randomized 1:1 to receive a 5 day course of mupirocin applied to the nares, umbilicus and perianal (NUP) areas every 8 hours (± 2 hours) vs. no treatment. (Stratification by birth gestational age is performed to minimize bias that could result from a higher risk for developing infection due to prematurity or prolonged length of stay due to prematurity.) The primary objectives of this study are to 1) 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 on days 8 (±2) and 22 (±2) (persistent decolonization). The secondary objectives of this study are to 1) To examine the efficacy of mupirocin in preventing clinical SA infection during days 1-22 or until discharge, whichever occurs first, among SA colonized infants who are residing in the ICU 2) To compare time until SA decolonization between the mupirocin and placebo groups: Time from Day 1 until the first NUP collection with no SA is detected in the nares, umbilical, and perianal areas 3) To examine whether mupirocin affects the frequency of non-SA clinical infections by comparing the frequency of these infections in the treatment and control groups during the 85 day observation period 4) To examine whether mupirocin affects the frequency of severe (stage II-III) necrotizing enterocolitis by comparing the frequency of occurrence in the treatment and control groups during the 85 day observation period.

Each participant will be enrolled for up to 12 weeks (Day 85) or until the time of discharge from the hospital, death or withdrawal from further participation, whichever occurs first. It is anticipated that it will take at least 2 years to enroll all participants. Study 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 toward the primary endpoint with 126 participants. Enrollment may continue up to a maximum of 500 participants to inform the secondary and exploratory endpoints and to help design any subsequent study.

Conditions

Staphylococcal Infection

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: PREVENTION

Study Groups

Group 1

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

Group Type: EXPERIMENTAL

Mupirocin calcium

Intervention Type: DRUG

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

Mupirocin calcium

Intervention Type: DRUG

Mupirocin calcium ointment 2% will be applied intranasally every 8 hours for 5 days, for a total of 15 applications

Group 2

No treatment

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

Mupirocin calcium

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

Intervention Type: DRUG

Mupirocin calcium

Mupirocin calcium ointment 2% will be applied intranasally every 8 hours for 5 days, for a total of 15 applications

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. 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

Exclusion Criteria

1. Receipt of an investigational drug as part of a research trial within the past 14 days 2. Previously enrolled and participated in this trial 3. Has an active or previous SA infection 4. Currently receiving topical or intranasal mupirocin 5. Has a rash in an area to which mupirocin will be directly applied 6. Has any of the following congenital abnormalities: --A congenital skin disorder (i.e. - epidermolysis bullosa, icthyosis) --An opened neural tube defect --Confirmed or suspected choanal atresia --Any of the following abdominal wall defects: wound dehiscence, gastroschisis, open abdominal wound (small abdominal wall defects such as ostomy sites or peritoneal drain sites are not exclusionary) 7. Is nasally intubated 8. Known hypersensitivity to the trial product or its constituents 9. Known or suspected immune deficiency. Infants born to HIV-seropositive mothers with the following risk factors for intrapartum transmission will not be eligible to participate: --Mother's most recent viral load within the past 3 months was > 1,000 copies/ml or --Mother's viral load is not known or has has not been measured in the past 3 months. 10. Any other condition(s) that in the opinion of the investigator would jeopardize the safety or rights of a participant or would render the participant unable to comply with the protocol

• Maximum Eligible Age: 24 Months
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institute of Allergy and Infectious Diseases (NIAID)

NIH

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Emory University Hospital Midtown - Neonatal Intensive Care Unit

Atlanta, Georgia, United States

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

Baltimore, Maryland, United States

Children's Mercy Hospital and Clinics - Infectious Diseases

Kansas City, Missouri, United States

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

St Louis, Missouri, United States

Cincinnati Children's Hospital Medical Center - Infectious Diseases

Cincinnati, Ohio, United States

Vanderbilt University - Pediatric - Vanderbilt Vaccine Research Center

Nashville, Tennessee, United States

Countries

United States

References

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.

Reference Type: DERIVED

PMID: 30587533 (View on PubMed)

Other Identifiers

09-0065

Identifier Type: -

Identifier Source: org_study_id