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Safety and Efficacy of Intranasal and Topical Mupirocin in Eradicating Colonization With Staphylococcus Aureus (SA) in Critically Ill Infants - a Phase 2, Multi-Center, Open Label, Randomized Trial

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT01827358
First received: April 4, 2013
Last updated: October 27, 2016
Last verified: April 2016
  Purpose
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.

Condition Intervention Phase
Staphylococcal Infection
Drug: Mupirocin calcium
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Prevention
Official Title: Safety and Efficacy of Intranasal and Topical Mupirocin in Eradicating Colonization With Staphylococcus Aureus (SA) in Critically Ill Infants - a Phase 2, Multi-Center, Open Label, Randomized Trial

Resource links provided by NLM:


Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Primary Outcome Measures:
  • Persistent decolonization efficacy- Proportion of infants in the treatment and control groups who have no detectable SA on direct NUP cultures on day 22(+/-2). [ Time Frame: Day 22 ] [ Designated as safety issue: No ]
  • Primary decolonization efficacy- Proportion of infants in the treatment and control groups who have no detectable S. aureus (SA) on direct NUP cultures obtained on day 8(+/-2). [ Time Frame: Day 8 ] [ Designated as safety issue: No ]
  • Safety- Frequency of (i) solicited adverse events(AEs), (ii) moderate and severe unsolicited AEs (that are not otherwise considered pre-defined trial endpoints); and (iii) serious adverse events (SAEs) during days 1-7. [ Time Frame: Days 1 through 7 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Median time to occurrence of non-SA clinical infection in the treatment compared to control group [ Time Frame: Day 1 through 85 ] [ Designated as safety issue: No ]
  • Median time to occurrence of severe (stage II-III) necrotizing enterocolitis (NEC) in the treatment compared to control group. [ Time Frame: Day 1 through 85 ] [ Designated as safety issue: No ]
  • Protective efficacy of clinical SA infection in the treatment compared to the control group during days 1-22 or until discharge, whichever occurs first. [ Time Frame: Day 1 through 22 ] [ Designated as safety issue: No ]
  • Relative risk of occurrence of non-SA clinical infection in the treatment compared to control group [ Time Frame: Day 1 through 85 ] [ Designated as safety issue: No ]
  • Relative risk of severe (stage II-III) necrotizing enterocolitis (NEC) in the treatment compared to control group [ Time Frame: Day 1 through 85 ] [ Designated as safety issue: No ]
  • Time until decolonization: Time from Day 1 until the first NUP collection with no SA is detected in the nares, umbilical, and perianal areas [ Time Frame: Day 1 through 85 ] [ Designated as safety issue: No ]

Enrollment: 155
Study Start Date: April 2014
Study Completion Date: June 2016
Primary Completion Date: June 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 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
Drug: 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
Drug: Mupirocin calcium
Mupirocin calcium ointment 2% will be applied intranasally every 8 hours for 5 days, for a total of 15 applications
No Intervention: Group 2
No treatment

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.

  Eligibility

Ages Eligible for Study:   up to 24 Months   (Child)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01827358

Locations
United States, Georgia
Emory University Hospital Midtown - Neonatal Intensive Care Unit
Atlanta, Georgia, United States, 30308-2208
United States, Maryland
University of Maryland Medical Center - Children's Hospital - Neonatal Intensive Care Unit
Baltimore, Maryland, United States, 21201-1595
United States, Missouri
Children's Mercy Hospital and Clinics - Infectious Diseases
Kansas City, Missouri, United States, 64108-4619
Saint Louis University School of Medicine - Cardinal Glennon Children's Medical Center - NICU
Saint Louis, Missouri, United States, 63104-1003
United States, Ohio
Cincinnati Children's Hospital Medical Center - Infectious Diseases
Cincinnati, Ohio, United States, 45229-3026
United States, Tennessee
Vanderbilt University - Pediatric - Vanderbilt Vaccine Research Center
Nashville, Tennessee, United States, 37232-2573
Sponsors and Collaborators
National Institute of Allergy and Infectious Diseases (NIAID)
  More Information

Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT01827358     History of Changes
Other Study ID Numbers: 09-0065  HHSN272200800057C 
Study First Received: April 4, 2013
Last Updated: October 27, 2016
Health Authority: United States: Federal Government
United States: Food and Drug Administration
United States: Institutional Review Board

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
antibacterial agent,children,colonisation,critically ill,infants,mupirocin,prevention,Staphylococcus aureus

Additional relevant MeSH terms:
Critical Illness
Staphylococcal Infections
Disease Attributes
Pathologic Processes
Gram-Positive Bacterial Infections
Bacterial Infections
Calcium, Dietary
Mupirocin
Bone Density Conservation Agents
Physiological Effects of Drugs
Anti-Bacterial Agents
Anti-Infective Agents
Protein Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on December 05, 2016