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Trial record 21 of 49 for:    necrotizing enterocolitis | NIH

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

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ClinicalTrials.gov Identifier: NCT01827358
Recruitment Status : Completed
First Posted : April 9, 2013
Results First Posted : July 7, 2017
Last Update Posted : July 7, 2017
Sponsor:
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Single Group Assignment;   Primary Purpose: Prevention
Condition Staphylococcal Infection
Intervention Drug: Mupirocin calcium
Enrollment 155
Recruitment Details Infants less than 24 months of age were recruited from among those admitted to the NICU or ICU at one of the participating centers found to have a surveillance nasal swab culture positive for SA. Recruitment was performed sequentially as infants became eligible without regards for race, ethnicity, gestational age or gender.
Pre-assignment Details Infants were screened for nasal SA colonization (MRSA or MSSA) and only those who were colonized (not infected) were offered enrollment.
Arm/Group Title Mupirocin (Treatment) No Mupirocin (Control)
Hide Arm/Group Description Participants received 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 Participants received no treatment or placebo
Period Title: Overall Study
Started 80 75
Completed 45 44
Not Completed 35 31
Arm/Group Title Mupirocin (Treatment) No Mupirocin (Control) Total
Hide Arm/Group Description Participants received 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 Participants received no treatment or placebo Total of all reporting groups
Overall Number of Baseline Participants 80 75 155
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 80 participants 75 participants 155 participants
<=18 years
80
 100.0%
75
 100.0%
155
 100.0%
Between 18 and 65 years
0
   0.0%
0
   0.0%
0
   0.0%
>=65 years
0
   0.0%
0
   0.0%
0
   0.0%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Weeks
Number Analyzed 80 participants 75 participants 155 participants
4.6  (3.6) 4.8  (4.4) 4.7  (4.0)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 80 participants 75 participants 155 participants
Female
35
  43.8%
33
  44.0%
68
  43.9%
Male
45
  56.3%
42
  56.0%
87
  56.1%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 80 participants 75 participants 155 participants
Hispanic or Latino
2
   2.5%
4
   5.3%
6
   3.9%
Not Hispanic or Latino
76
  95.0%
66
  88.0%
142
  91.6%
Unknown or Not Reported
2
   2.5%
5
   6.7%
7
   4.5%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 80 participants 75 participants 155 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
Asian
1
   1.3%
1
   1.3%
2
   1.3%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
22
  27.5%
25
  33.3%
47
  30.3%
White
50
  62.5%
41
  54.7%
91
  58.7%
More than one race
6
   7.5%
7
   9.3%
13
   8.4%
Unknown or Not Reported
1
   1.3%
1
   1.3%
2
   1.3%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 80 participants 75 participants 155 participants
80 75 155
1.Primary Outcome
Title Number of Participants With Solicited Adverse Events (AEs) During Days 1-7
Hide Description 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.
Time Frame Days 1 through 7
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The analysis population was comprised of all infants, categorized according to treatment group. The number of infants is different from the overall study participant counts as 2 participants randomized to the mupirocin group received no mupirocin. For the purpose of safety analysis, these were included in the control (no mupirocin) group.
Arm/Group Title Mupirocin (Treatment) No Mupirocin (Control)
Hide Arm/Group Description:
Participants received 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.
Participants received no treatment and no placebo.
Overall Number of Participants Analyzed 78 77
Measure Type: Number
Unit of Measure: participants
Fever 2 1
Rash 17 4
Swelling of nasal mucosa 1 0
Epistaxis 0 0
Diarrhea 9 7
Apnea/ bradycardia/ desaturation events 43 45
Apnea within 3-5 minutes of mupirocin application 8 NA [1] 
Pain within 3-5 minutes of mupirocin application 15 NA [1] 
Any Symptom 60 65
[1]
Participants in the No Mupirocin (Control) group did not receive mupirocin
2.Primary Outcome
Title Number of Participants With Moderate and Severe Unsolicited Adverse Events; During Days 1-7
Hide Description 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.
Time Frame Days 1 through 7
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The analysis population was comprised of all infants, categorized according to treatment group. The number of infants is different from the overall study participant counts as 2 participants randomized to the mupirocin group received no mupirocin. For the purpose of safety analysis, these were included in the control (no mupirocin) group.
Arm/Group Title Mupirocin (Treatment) No Mupirocin (Control)
Hide Arm/Group Description:
Participants received 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.
Participants received no treatment and no placebo.
Overall Number of Participants Analyzed 78 77
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: participants
Cardiac failure
1
(0 to 7)
0
(0 to 5)
Heart disease congenital
1
(0 to 7)
0
(0 to 5)
Incarcerated inguinal hernia
1
(0 to 7)
0
(0 to 5)
Necrotising colitis
0
(0 to 5)
1
(0 to 7)
Candida infection
1
(0 to 7)
0
(0 to 5)
Pneumonia
1
(0 to 7)
0
(0 to 5)
Rhinovirus infection
0
(0 to 5)
1
(0 to 7)
3.Primary Outcome
Title Number of Participants With Serious Adverse Events (SAEs) During Days 1-7
Hide Description 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.
Time Frame Days 1 through 7
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The analysis population was comprised of all infants, categorized according to treatment group. The number of infants is different from the overall study participant counts as 2 participants randomized to the mupirocin group received no mupirocin. For the purpose of safety analysis, these were included in the control (no mupirocin) group.
Arm/Group Title Mupirocin (Treatment) No Mupirocin (Control)
Hide Arm/Group Description:
Participants received 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.
Participants received no treatment and no placebo.
Overall Number of Participants Analyzed 78 77
Measure Type: Count of Participants
Unit of Measure: Participants
Staphylococcal bacteremia
1
   1.3%
0
   0.0%
Heart disease congenital
1
   1.3%
0
   0.0%
Incarcerated inguinal hernia
1
   1.3%
0
   0.0%
Infantile apnoea
1
   1.3%
0
   0.0%
4.Primary Outcome
Title 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.
Hide Description 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.
Time Frame Day 8
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The analysis population included all infants with a site-specific pre-randomization NUP culture that was positive for SA by direct culture and who either had a complete set of NUP cultures collected on Day 8 or else had discontinued NUP cultures prior to day 8 due to a clinical SA infection.
Arm/Group Title Mupirocin (Treatment) No Mupirocin (Control)
Hide Arm/Group Description:
Participants received 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.
Participants received no treatment and no placebo.
Overall Number of Participants Analyzed 66 64
Measure Type: Count of Participants
Unit of Measure: Participants
62
  93.9%
3
   4.7%
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Mupirocin (Treatment)
Comments [Not Specified]
Type of Statistical Test Other
Comments For strong control of the family-wise error rate at the 0.05 confidence level, the Holm procedure (Holm 1979) is used. Under this procedure, the p-values from the two tests are sorted as p_((1)) (smaller p-value) and p_((2)) (larger p-value). If p_((1))=0.025 and p_((2))=0.05, then the null hypotheses for both tests are rejected. If p_((1))=0.025 and p_((2))>0.05, then only the null hypothesis associated with the smaller p-value is rejected. In any other case, neither null hypothesis is rejected
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 315.2
Confidence Interval (2-Sided) 97.5%
49.6 to 2698.8
Estimation Comments [Not Specified]
5.Primary Outcome
Title 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.
Hide Description 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.
Time Frame Day 8 and Day 22
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The analysis population included all infants with a site-specific pre-randomization NUP culture that was positive for SA by direct culture and who had either had complete sets of NUP cultures collected on day 8 and day 22 or else had discontinued NUP cultures prior to day 22 due to a clinical SA infection.
Arm/Group Title Mupirocin (Treatment) No Mupirocin (Control)
Hide Arm/Group Description:
Participants received 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.
Participants received no treatment and no placebo.
Overall Number of Participants Analyzed 46 48
Measure Type: Count of Participants
Unit of Measure: Participants
21
  45.7%
1
   2.1%
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Mupirocin (Treatment)
Comments [Not Specified]
Type of Statistical Test Other
Comments For strong control of the family-wise error rate at the 0.05 confidence level, the Holm procedure (Holm 1979) is used. Under this procedure, the p-values from the two tests are sorted as p_((1)) (smaller p-value) and p_((2)) (larger p-value). If p_((1))=0.025 and p_((2))=0.05, then the null hypotheses for both tests are rejected. If p_((1))=0.025 and p_((2))>0.05, then only the null hypothesis associated with the smaller p-value is rejected. In any other case, neither null hypothesis is rejected
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 39.5
Confidence Interval (2-Sided) 95%
5.5 to 1666.3
Estimation Comments [Not Specified]
6.Secondary Outcome
Title Relative Risk of Occurrence of Non-SA Clinical Infection in the Treatment Compared to Control Group in the Intent To Treat Cohort
Hide Description Relative risk of occurrence of non-SA clinical infection in the treatment compared to the control group using the intent to treat (ITT) cohort for analysis. The time periods in the table correspond to the study days having scheduled collection of nasal, umbilical, and perianal (NUP) cultures. At risk participants were eligible for the non-SA clinical infection to occur at the start of the interval, were still on study and had not yet had a non-SA clinical infection but were still being watched for the event. Non-SA clinical infection was the development of a non-SA clinical infection due to an identifiable organism as evidenced by culture of an organism other than SA from a normally sterile body site or an infant who met the clinical diagnosis of localized infection as defined in the protocol. Censored participants were at risk for some of the interval, did not have a non-SA clinical infection but were removed from eligibility for the event at some point after the interval started.
Time Frame Day 1 through 85
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The ITT cohort included all randomized infants. The analyses on the ITT cohort were performed per randomized treatment assignment.
Arm/Group Title Mupirocin (Treatment) No Mupirocin (Control)
Hide Arm/Group Description:
Participants received 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.
Participants received no treatment and no placebo.
Overall Number of Participants Analyzed 80 75
Measure Type: Count of Participants
Unit of Measure: Participants
Day 1-8 at risk
78
  97.5%
73
  97.3%
Day 1-8 with clinical non-SA infection
3
   3.8%
1
   1.3%
Day 1-8 censored
4
   5.0%
6
   8.0%
Day 9-15 at risk
71
  88.8%
66
  88.0%
Day 9-15 with clinical non-SA infection
0
   0.0%
0
   0.0%
Day 9-15 censored
11
  13.8%
12
  16.0%
Day 16-22 at risk
60
  75.0%
54
  72.0%
Day 16-22 with clinical non-SA infection
0
   0.0%
0
   0.0%
Day 16-22 censored
12
  15.0%
4
   5.3%
Day 23-29 at risk
48
  60.0%
50
  66.7%
Day 23-29 with clinical non-SA infection
0
   0.0%
3
   4.0%
Day 23-29 censored
4
   5.0%
14
  18.7%
Day 30-36 at risk
44
  55.0%
33
  44.0%
Day 30-36 with clinical non-SA infection
1
   1.3%
1
   1.3%
Day 30-36 censored
6
   7.5%
6
   8.0%
Day 37-43 at risk
37
  46.3%
26
  34.7%
Day 37-43 with clinical non-SA infection
1
   1.3%
0
   0.0%
Day 37-43 censored
4
   5.0%
7
   9.3%
Day 44-50 at risk
32
  40.0%
19
  25.3%
Day 44-50 with clinical non-SA infection
0
   0.0%
0
   0.0%
Day 44-50 censored
9
  11.3%
6
   8.0%
Day 51-57 at risk
23
  28.7%
13
  17.3%
Day 51-57 with clinical non-SA infection
1
   1.3%
0
   0.0%
Day 51-57 censored
0
   0.0%
3
   4.0%
Day 58-64 at risk
22
  27.5%
10
  13.3%
Day 58-64 with clinical non-SA infection
0
   0.0%
0
   0.0%
Day 58-64 censored
5
   6.3%
5
   6.7%
Day 65-71 at risk
17
  21.3%
5
   6.7%
Day 65-71 with clinical non-SA infection
0
   0.0%
0
   0.0%
Day 65-71 censored
6
   7.5%
1
   1.3%
Day 72-78 at risk
11
  13.8%
4
   5.3%
Day 72-78 with clinical non-SA infection
0
   0.0%
0
   0.0%
Day 72-78 censored
3
   3.8%
0
   0.0%
Day 79-85 at risk
8
  10.0%
4
   5.3%
Day 79-85 with clinical non-SA infection
0
   0.0%
0
   0.0%
Day 79-85 censored
8
  10.0%
4
   5.3%
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Mupirocin (Treatment)
Comments The association between mupirocin treatment and non-clinical SA Infection on or before Day 85 was assessed via a Cox Proportional Hazards Model. Onset time was defined as the first day of non-SA infection. Infants were right-censored at the time of discharge from the hospital or at Day 85, whichever came first.
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.997
Comments [Not Specified]
Method Cox proportional hazards model
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.00
Confidence Interval (2-Sided) 95%
0.30 to 3.28
Estimation Comments [Not Specified]
7.Secondary Outcome
Title Relative Risk of Occurrence of Non-SA Clinical Infection in the Treatment Compared to Control Group in the According to Protocol Cohort.
Hide Description Relative risk of occurrence of non-SA clinical infection in the treatment compared to control groups using the according to protocol (ATP) cohort. The time periods in the table correspond to the study days having scheduled collection of nasal, umbilical, and perianal (NUP) cultures. At risk participants were eligible for the non-SA clinical infection to occur at the start of the interval, were still on study and had not yet had a non-SA clinical infection but were still being watched for the event. Non-SA clinical infection was the development of a non-SA clinical infection due to an identifiable organism as evidenced by culture of an organism other than SA from a normally sterile body site or an infant who met the clinical diagnosis of localized infection as defined in the protocol. Censored participants were at risk for some of the interval, did not have a non-SA clinical infection but were removed from eligibility for the event at some point after the interval started.
Time Frame Day 1 through 85
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The ATP cohort includes all infants with a site-specific pre-randomization NUP culture that is positive for SA by direct culture, those in the mupirocin treatment group must have received a minimum of 10 complete mupirocin treatments, including at least one dose to all three NUP sites per day for five consecutive days during the treatment period.
Arm/Group Title Mupirocin (Treatment) No Mupirocin (Control)
Hide Arm/Group Description:
Participants received 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.
Participants received no treatment and no placebo.
Overall Number of Participants Analyzed 67 66
Measure Type: Count of Participants
Unit of Measure: Participants
Day 1-8 at risk
67
 100.0%
66
 100.0%
Day 1-8 with clinical non-SA infection
3
   4.5%
1
   1.5%
Day 1-8 censored
3
   4.5%
4
   6.1%
Day 9-15 at Risk
61
  91.0%
61
  92.4%
Day 9-15 with clinical non-SA infection
0
   0.0%
0
   0.0%
Day 9-15 censored
9
  13.4%
11
  16.7%
Day 16-22 at risk
52
  77.6%
50
  75.8%
Day 16-22 with non-SA infection
0
   0.0%
0
   0.0%
Day 16-22 censored
11
  16.4%
4
   6.1%
Day 23-29 at risk
41
  61.2%
46
  69.7%
Day 23-29 with clinical non-SA infection
0
   0.0%
3
   4.5%
Day 23-29 censored
4
   6.0%
13
  19.7%
Day 30-36 at risk
37
  55.2%
30
  45.5%
Day 30-36 with clinical non-SA infection
1
   1.5%
0
   0.0%
Day 30-36 censored
4
   6.0%
6
   9.1%
Day 37-43 at risk
32
  47.8%
24
  36.4%
Day 37-43 with clinical non-SA infection
1
   1.5%
0
   0.0%
Day 37-43 censored
4
   6.0%
7
  10.6%
Day 44-50 at risk
27
  40.3%
17
  25.8%
Day 44-50 with clinical non-SA infection
0
   0.0%
0
   0.0%
Day 44-50 censored
8
  11.9%
6
   9.1%
Day 51-57 at risk
19
  28.4%
11
  16.7%
Day 51-57 with clinical non-SA infection
1
   1.5%
0
   0.0%
Day 51-57 censored
0
   0.0%
2
   3.0%
Day 58-64 at risk
18
  26.9%
9
  13.6%
Day 58-64 with clinical non-SA infection
0
   0.0%
0
   0.0%
Day 58-64 censored
4
   6.0%
4
   6.1%
Day 65-71 at risk
14
  20.9%
5
   7.6%
Day 65-71 with clinical non-SA infection
0
   0.0%
0
   0.0%
Day 65-71 censored
5
   7.5%
1
   1.5%
Day 72-78 at risk
9
  13.4%
4
   6.1%
Day 72-78 with clinical non-SA infection
0
   0.0%
0
   0.0%
Day 72-78 censored
3
   4.5%
0
   0.0%
Day 79-85 at risk
6
   9.0%
4
   6.1%
Day 79-85 with clinical non-SA infection
0
   0.0%
0
   0.0%
Day 79-85 censored
6
   9.0%
4
   6.1%
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Mupirocin (Treatment)
Comments The association between mupirocin treatment and non-clinical SA Infection on or before Day 85 was assessed via a Cox Proportional Hazards Model. Onset time was defined as the first day of non-SA infection. Infants were right-censored at the time of discharge from the hospital or at Day 85, whichever came first.
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.656
Comments [Not Specified]
Method Cox proportional hazards model
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.33
Confidence Interval (2-Sided) 95%
0.37 to 4.76
Estimation Comments [Not Specified]
8.Secondary Outcome
Title Median Time to Occurrence of Severe (Stage II-III) Necrotizing Enterocolitis (NEC) in the Treatment Compared to Control Group.
Hide Description Median time to occurrence of severe (stage II-III) NEC in the treatment compared to control group as estimated using Kaplan-Meier estimates of the survival curves.
Time Frame Day 1 through 85
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
There were no events of necrotizing enterocolitis during the study, analysis could not be performed.
Arm/Group Title Mupirocin (Treatment) No Mupirocin (Control)
Hide Arm/Group Description:
Participants received 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.
Participants received no treatment and no placebo.
Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
9.Secondary Outcome
Title 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.
Hide Description 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 intent to treat (ITT) cohort. The time periods in the table correspond to the study days having scheduled collection of nasal, umbilical, and perianal (NUP) cultures. At risk participants were eligible for the SA clinical infection to occur at the start of the interval, were still on study and had not yet had a SA clinical infection but were still being watched for the event. SA clinical infection was the development of a SA clinical infection due to an identifiable organism as evidenced by culture of an organism from a normally sterile body site or an infant who met the clinical diagnosis of localized infection as defined in the protocol. Censored participants were at risk for some of the interval, did not have a SA clinical infection but were removed from eligibility for the event at some point after the interval started.
Time Frame Day 1 through 22
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The ITT cohort included all randomized infants. The analyses on the ITT cohort were performed per randomized treatment assignment.
Arm/Group Title Mupirocin (Treatment) No Mupirocin (Control)
Hide Arm/Group Description:
Participants received 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.
Participants received no treatment and no placebo.
Overall Number of Participants Analyzed 80 75
Measure Type: Count of Participants
Unit of Measure: Participants
Day 1-8 at risk
78
  97.5%
73
  97.3%
Day 1-8 with clinical SA infection
0
   0.0%
2
   2.7%
Day 1-8 censored
5
   6.3%
6
   8.0%
Day 9-15 at risk
73
  91.3%
65
  86.7%
Day 9-15 with clinical SA infection
1
   1.3%
1
   1.3%
Day 9-15 censored
11
  13.8%
12
  16.0%
Day 16-22 at risk
61
  76.3%
52
  69.3%
Day 16-22 with clinical SA infection
0
   0.0%
1
   1.3%
Day 16-22 censored
61
  76.3%
51
  68.0%
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Mupirocin (Treatment)
Comments The time to clinical infection with SA on or prior to Day 22 was analyzed using Kaplan-Meier estimates of the survival curve and Cox proportional hazards models (with treatment as the only independent variable). Infants were censored at Day 22 or completion or early termination from the study. Estimates of the hazard ratio (values less than one indicating a treatment benefit) with Wald 95% confidence intervals and accompanying p-values were calculated.
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.182
Comments [Not Specified]
Method Cox proportional hazards models
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.23
Confidence Interval (2-Sided) 95%
0.03 to 2.01
Estimation Comments [Not Specified]
10.Secondary Outcome
Title 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.
Hide Description 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 ATP cohort. The time periods in the table correspond to the study days having scheduled collection of nasal, umbilical, and perianal (NUP) cultures. At risk participants were eligible for the SA clinical infection to occur at the start of the interval, were still on study and had not yet had a SA clinical infection but were still being watched for the event. SA clinical infection was the development of a SA clinical infection due to an identifiable organism as evidenced by culture of an organism from a normally sterile body site or an infant who met the clinical diagnosis of localized infection as defined in the protocol. Censored participants were at risk for some of the interval, did not have a SA clinical infection but were removed from eligibility for the event at some point after the interval started.
Time Frame Day 1 through 22
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The ATP cohort includes all infants that have met all requirements of the mITT cohort, with the further requirements that infants in the mupirocin treatment group must have received a minimum of 10 complete mupirocin treatments, including at least one dose to all three NUP sites per day for five consecutive days during the treatment period.
Arm/Group Title Mupirocin (Treatment) No Mupirocin (Control)
Hide Arm/Group Description:
Participants received 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.
Participants received no treatment and no placebo.
Overall Number of Participants Analyzed 67 66
Measure Type: Count of Participants
Unit of Measure: Participants
Day 1-8 at risk
67
 100.0%
66
 100.0%
Day 1-8 with clinical SA infection
0
   0.0%
2
   3.0%
Day 1-8 censored
4
   6.0%
4
   6.1%
Day 9-15 at risk
63
  94.0%
60
  90.9%
Day 9-15 with clinical SA infection
1
   1.5%
1
   1.5%
Day 9-15 censored
9
  13.4%
11
  16.7%
Day 16-22 at risk
53
  79.1%
48
  72.7%
Day 16-22 with clinical SA infection
0
   0.0%
1
   1.5%
Day 16-22 censored
53
  79.1%
47
  71.2%
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Mupirocin (Treatment)
Comments The time to clinical infection with SA on or prior to Day 22 was analyzed using Kaplan-Meier estimates of the survival curve and Cox proportional hazards models (with treatment as the only independent variable). Infants were censored at Day 22 or completion or early termination from the study. Estimates of the hazard ratio (values less than one indicating a treatment benefit) with Wald 95% confidence intervals and accompanying p-values were calculated.
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.198
Comments [Not Specified]
Method Cox proportional hazards model
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.24
Confidence Interval (2-Sided) 95%
0.03 to 2.12
Estimation Comments [Not Specified]
11.Secondary Outcome
Title Median Time to Occurrence of Non-S. Aureus (SA) Clinical Infection in the Treatment Compared to Control Group
Hide Description Median time to occurrence of non-SA clinical infection in the treatment compared to control group as estimated using Kaplan-Meier estimates of the survival curves.
Time Frame Day 1 through 85
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Clinical infection besides SA infection on or prior to Day 85 was not observed frequently enough to allow estimation of the median time to infection using non-parametric methods.
Arm/Group Title Mupirocin (Treatment) No Mupirocin (Control)
Hide Arm/Group Description:
Participants received 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.
Participants received no treatment and no placebo.
Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
12.Secondary Outcome
Title Relative Risk of Severe (Stage II-III) Necrotizing Enterocolitis (NEC) in the Treatment Compared to Control Group
Hide Description The association between mupirocin treatment and severe (stage II-III) NEC on or before Day 85 was to be assessed via Cox Proportional Hazards Model.
Time Frame Day 1 through 85
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
There were no events of necrotizing enterocolitis during the study, analysis could not be performed.
Arm/Group Title Mupirocin (Treatment) No Mupirocin (Control)
Hide Arm/Group Description:
Participants received 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.
Participants received no treatment and no placebo.
Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
13.Secondary Outcome
Title Time Until Decolonization: Count of Participants From Day 1 Until the First NUP Collection With no S. Aureus (SA) Detected in the Nares, Umbilical, and Perianal Areas Using the Modified Intent to Treat Day 8 Cohort (mITT-8).
Hide Description Time until decolonization: Count of participants from Day 1 until the first NUP collection with no SA is detected in the nares, umbilical, and perianal areas using the modified intent to treat (mITT-8) cohort. The time periods in the table correspond to the study days having collection of nasal, umbilical, and perianal (NUP) cultures. At risk participants were eligible for the SA decolonization to occur at the start of the interval, were still on study and had not yet had SA decolonization but were still being watched for the event. SA decolonization was the absence of SA detected from the NUP cultures through direct plating. Censored participants were at risk for some of the interval, did not have SA decolonization but were removed from eligibility for the event at some point after the interval started.
Time Frame Day 1 through 85
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The mITT cohort includes all infants with a site-specific pre-randomization NUP culture that was positive for SA by direct culture. The mITT-8 cohort includes all mITT infants who either had a complete set of NUP cultures collected on day 8 or else had discontinuation of NUP cultures prior to Day 8 due to a clinical SA infection.
Arm/Group Title Mupirocin (Treatment) No Mupirocin (Control)
Hide Arm/Group Description:
Participants received 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.
Participants received no treatment and no placebo.
Overall Number of Participants Analyzed 66 64
Measure Type: Count of Participants
Unit of Measure: Participants
Day 1-8 at risk
66
 100.0%
64
 100.0%
Day 1-8 with decolonization
59
  89.4%
3
   4.7%
Day 1-8 censored
1
   1.5%
14
  21.9%
Day 9-15 at risk
6
   9.1%
47
  73.4%
Day 9-15 with decolonization
3
   4.5%
0
   0.0%
Day 9-15 censored
0
   0.0%
4
   6.3%
Day 16-22 at risk
3
   4.5%
43
  67.2%
Day 16-22 with decolonization
0
   0.0%
0
   0.0%
Day 16-22 censored
3
   4.5%
43
  67.2%
14.Secondary Outcome
Title Time Until Decolonization: Count of Participants From Day 1 Until the First NUP Collection With no SA is Detected in the Nares, Umbilical, and Perianal Areas Using the According to Protocol Day 8 (ATP-8) Cohort.
Hide Description Time until decolonization: Count of participants from Day 1 until the first NUP collection with no SA is detected in the nares, umbilical, and perianal areas using the according to protocol day 8 (ATP-8) cohort. The time periods in the table correspond to the study days having scheduled collection of nasal, umbilical, and perianal (NUP) cultures. At risk participants were eligible for the SA decolonization to occur at the start of the interval, were still on study and had not yet had SA decolonization but were still being watched for the event. SA decolonization was the absence of SA detected from the NUP cultures through direct plating. Censored participants were at risk for some of the interval, did not have SA decolonization but were removed from eligibility for the event at some point after the interval started.
Time Frame Day 1 through 85
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The ATP-8 cohort includes all ATP infants who had a set of NUP cultures collected on Day 8 (± 2).
Arm/Group Title Mupirocin (Treatment) No Mupirocin (Control)
Hide Arm/Group Description:
Participants received 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.
Participants received no treatment and no placebo.
Overall Number of Participants Analyzed 64 63
Measure Type: Count of Participants
Unit of Measure: Participants
Day 1-8 at risk
64
 100.0%
63
 100.0%
Day 1-8 with decolonization
57
  89.1%
2
   3.2%
Day 1-8 censored
1
   1.6%
14
  22.2%
Day 9-15 at risk
6
   9.4%
47
  74.6%
Day 9-15 with decolonization
3
   4.7%
0
   0.0%
Day 9-15 censored
0
   0.0%
4
   6.3%
Day 16-22 at risk
3
   4.7%
43
  68.3%
Day 16-22 with decolonization
0
   0.0%
0
   0.0%
Day 16-22 censored
3
   4.7%
43
  68.3%
Time Frame Adverse events were collected on days 1-7.
Adverse Event Reporting Description For days 1-7, study staff were responsible for identifying solicited adverse events (AEs), unsolicited moderate and severe AEs and serious adverse events (SAEs) on a daily basis. Solicited adverse events of apnea within 3-5 minutes of mupirocin application and pain within 3-5 minutes of mupirocin application, were not applicable to the control group since they did not receive mupirocin.
 
Arm/Group Title Mupirocin (Treatment) No Mupirocin (Control)
Hide Arm/Group Description Participants 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 Participants received no treatment and no placebo.
All-Cause Mortality
Mupirocin (Treatment) No Mupirocin (Control)
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Mupirocin (Treatment) No Mupirocin (Control)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   3/80 (3.75%)      0/75 (0.00%)    
Congenital, familial and genetic disorders     
Heart disease congenital * 1  1/80 (1.25%)  1 0/75 (0.00%)  0
Gastrointestinal disorders     
Incarcerated inguinal hernia * 1  1/80 (1.25%)  1 0/75 (0.00%)  0
Infections and infestations     
Staphylococcal bacteraemia * 1  1/80 (1.25%)  1 0/75 (0.00%)  0
Respiratory, thoracic and mediastinal disorders     
Infantile apnoea * 1  1/80 (1.25%)  1 0/75 (0.00%)  0
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA (19.0)
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Mupirocin (Treatment) No Mupirocin (Control)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   60/78 (76.92%)      50/77 (64.94%)    
Gastrointestinal disorders     
Diarrhoea  1  9/78 (11.54%)  18 7/77 (9.09%)  14
General disorders     
Application site pain  1 [1]  15/78 (19.23%)  18 0/0  0
Injury, poisoning and procedural complications     
Administration related reaction  1  8/78 (10.26%)  9 0/0  0
Respiratory, thoracic and mediastinal disorders     
Apnea  1  43/78 (55.13%)  128 45/77 (58.44%)  129
Skin and subcutaneous tissue disorders     
Rash  1  17/78 (21.79%)  52 4/77 (5.19%)  12
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (19.0)
[1]
Administration site conditions
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Name/Title: Karen Kotloff, MD
Organization: University of Maryland Medical Center
Phone: 410-706-5328
Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT01827358     History of Changes
Other Study ID Numbers: 09-0065
First Submitted: April 4, 2013
First Posted: April 9, 2013
Results First Submitted: June 1, 2017
Results First Posted: July 7, 2017
Last Update Posted: July 7, 2017