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 is currently recruiting participants. (see Contacts and Locations)
Verified April 2014 by National Institute of Allergy and Infectious Diseases (NIAID)
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: July 24, 2014
Last verified: April 2014
  Purpose

To examine the safety and effectiveness of mupirocin in eradicating colonization with SA (MRSA or MSSA) and preventing the occurrence of invasive and other clinically significant SA infections among infants in the ICU. To evaluate the safety and clinical acceptability of a 5-day course (15 applications) of topical mupirocin applied every 8 hours (+/= 2 hours) daily to the nares, umbilicus and perianal area of infants residing in the ICU. Infants less than 24 months of age will be recruited from among those admitted to the NICU or ICU at one of the participating centers. 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.


Condition Intervention Phase
Staphylococcal Infection
Drug: Mupirocin cream
Drug: Mupirocin ointment
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:
  • Safety: Frequency of solicited adverse events(AEs), moderate and severe unsolicited AEs (that are not otherwise considered pre-defined trial endpoints), serious adverse events (SAEs) during days 1-7 and related SAEs until Day 85 [ Time Frame: Days 1 through 85 ] [ Designated as safety issue: Yes ]
  • Primary decolonization efficacy: Proportion of infants in the treatment and control groups who have no detectable S. aureus (SA) on direct cultures obtained on day 8 [ Time Frame: Day 8 ] [ Designated as safety issue: No ]
  • Persistent decolonization efficacy: Proportion of infants in the treatment and control groups who have no detectable SA on direct cultures on days 8 and 22 [ Time Frame: Days 8 and 22 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Protective efficacy and median time to occurrence of clinical SA infection in the treatment compared to the control group during days 1-22 or until discharge, whichever occurs first. [ Time Frame: Days 1 through 22 ] [ Designated as safety issue: No ]

Estimated Enrollment: 126
Study Start Date: April 2014
Estimated Primary Completion Date: June 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
No Intervention: Group 2
No treatment
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 cream
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 ointment
Mupirocin calcium ointment 2% will be applied intranasally every 8 hours for 5 days, for a total of 15 applications

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.) 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
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Currently admitted to a NICU or ICU at a participating site
  • Chronological age less than 24 months
  • Evidence of colonization with SA (MRSA or MSSA) based on a positive nasal surveillance culture. Randomization must occur within 120 hours of receipt of the nasal surveillance swab by the laboratory
  • The attending neonatologist/ intensivist anticipates that the infant will remain in the ICU for a minimum of 14 days after enrollment
  • Infant has never been discharged home since birth
  • 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:

  • Receipt of an investigational drug as part of a research trial within the past 14 days
  • Previously enrolled and participated in this trial
  • Has an active or previous SA infection or previous SA colonization
  • Currently receiving topical or intranasal mupirocin
  • Has a rash in an area to which mupirocin will be directly applied
  • 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)
  • Is nasally intubated
  • Known hypersensitivity to the trial product or its constituents
  • 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.
  • 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

Contacts
Contact: Karen L Kotloff (410) 706-5328 kkotloff@medicine.umaryland.edu

Locations
United States, Georgia
Emory University Hospital Midtown - Neonatal Intensive Care Unit Recruiting
Atlanta, Georgia, United States, 30308-2208
United States, Maryland
University of Maryland Medical Center - Children's Hospital - Neonatal Intensive Care Unit Not yet recruiting
Baltimore, Maryland, United States, 21201-1595
United States, Missouri
Children's Mercy Hospital and Clinics - Infectious Diseases Recruiting
Kansas City, Missouri, United States, 64108-4619
Saint Louis University School of Medicine - Cardinal Glennon Children's Medical Center - NICU Recruiting
Saint Louis, Missouri, United States, 63104-1003
United States, Ohio
Cincinnati Children's Hospital Medical Center - Infectious Diseases Recruiting
Cincinnati, Ohio, United States, 45229-3026
United States, Tennessee
Vanderbilt University - Pediatric - Vanderbilt Vaccine Research Center Recruiting
Nashville, Tennessee, United States, 37232-2573
Sponsors and Collaborators
  More Information

No publications provided

Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT01827358     History of Changes
Other Study ID Numbers: 09-0065, MRSA CVD 1000, N01AI80057C
Study First Received: April 4, 2013
Last Updated: July 24, 2014
Health Authority: United States: Food and Drug Administration
United States: Federal Government
United States: Institutional Review Board

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

Additional relevant MeSH terms:
Critical Illness
Staphylococcal Infections
Disease Attributes
Pathologic Processes
Gram-Positive Bacterial Infections
Bacterial Infections
Mupirocin
Protein Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Anti-Bacterial Agents
Anti-Infective Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on July 26, 2014