NCT01827358

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

Completed Phase 2 Results posted Last updated 7 July 2017

What this trial tests

Phase 2 trial testing Mupirocin calcium in Staphylococcal Infection in 155 participants. Completed in 21 June 2016.

Timeline

30 April 2014

Primary endpoint
7 June 2016

21 June 2016

Quick facts

Lead sponsor	National Institute of Allergy and Infectious Diseases (NIAID)
Phase	Phase 2
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	single group
Primary purpose	prevention
Enrollment	155
Start date	30 April 2014
Primary completion	7 June 2016
Estimated completion	21 June 2016
Sites	6 locations across United States

Drugs / interventions tested

• Mupirocin calcium — full drug profile →
• Mupirocin calcium — full drug profile →

Conditions studied

• Staphylococcal Infection — all drugs for Staphylococcal Infection →

Sponsor

National Institute of Allergy and Infectious Diseases (NIAID)

Who can join

Under 24 Months, any sex, with Staphylococcal Infection. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Number of Participants With Solicited Adverse Events (AEs) During Days 1-7 Primary · Days 1 through 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.

Fever

Group	Value	95% CI
Mupirocin (Treatment)	2
No Mupirocin (Control)	1

Rash

Group	Value	95% CI
Mupirocin (Treatment)	17
No Mupirocin (Control)	4

Swelling of nasal mucosa

Group	Value	95% CI
Mupirocin (Treatment)	1
No Mupirocin (Control)	0

Epistaxis

Group	Value	95% CI
Mupirocin (Treatment)	0
No Mupirocin (Control)	0

Diarrhea

Group	Value	95% CI
Mupirocin (Treatment)	9
No Mupirocin (Control)	7

Apnea/ bradycardia/ desaturation events

Group	Value	95% CI
Mupirocin (Treatment)	43
No Mupirocin (Control)	45

Apnea within 3-5 minutes of mupirocin application

Group	Value	95% CI
Mupirocin (Treatment)	8
No Mupirocin (Control)	NA

Pain within 3-5 minutes of mupirocin application

Group	Value	95% CI
Mupirocin (Treatment)	15
No Mupirocin (Control)	NA

Number of Participants With Moderate and Severe Unsolicited Adverse Events; During Days 1-7 Primary · Days 1 through 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.

Cardiac failure

Group	Value	95% CI
Mupirocin (Treatment)	1	0 – 7
No Mupirocin (Control)	0	0 – 5

Heart disease congenital

Group	Value	95% CI
Mupirocin (Treatment)	1	0 – 7
No Mupirocin (Control)	0	0 – 5

Incarcerated inguinal hernia

Group	Value	95% CI
Mupirocin (Treatment)	1	0 – 7
No Mupirocin (Control)	0	0 – 5

Necrotising colitis

Group	Value	95% CI
Mupirocin (Treatment)	0	0 – 5
No Mupirocin (Control)	1	0 – 7

Candida infection

Group	Value	95% CI
Mupirocin (Treatment)	1	0 – 7
No Mupirocin (Control)	0	0 – 5

Pneumonia

Group	Value	95% CI
Mupirocin (Treatment)	1	0 – 7
No Mupirocin (Control)	0	0 – 5

Rhinovirus infection

Group	Value	95% CI
Mupirocin (Treatment)	0	0 – 5
No Mupirocin (Control)	1	0 – 7

Number of Participants With Serious Adverse Events (SAEs) During Days 1-7 Primary · Days 1 through 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 pro

Staphylococcal bacteremia

Group	Value	95% CI
Mupirocin (Treatment)	1
No Mupirocin (Control)	0

Heart disease congenital

Group	Value	95% CI
Mupirocin (Treatment)	1
No Mupirocin (Control)	0

Incarcerated inguinal hernia

Group	Value	95% CI
Mupirocin (Treatment)	1
No Mupirocin (Control)	0

Infantile apnoea

Group	Value	95% CI
Mupirocin (Treatment)	1
No Mupirocin (Control)	0

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. Primary · 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.

Group	Value	95% CI
Mupirocin (Treatment)	62
No Mupirocin (Control)	3

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. Primary · Day 8 and Day 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

Group	Value	95% CI
Mupirocin (Treatment)	21
No Mupirocin (Control)	1

Relative Risk of Occurrence of Non-SA Clinical Infection in the Treatment Compared to Control Group in the Intent To Treat Cohort Secondary · Day 1 through 85

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

Day 1-8 at risk

Group	Value	95% CI
Mupirocin (Treatment)	78
No Mupirocin (Control)	73

Day 1-8 with clinical non-SA infection

Group	Value	95% CI
Mupirocin (Treatment)	3
No Mupirocin (Control)	1

Day 1-8 censored

Group	Value	95% CI
Mupirocin (Treatment)	4
No Mupirocin (Control)	6

Day 9-15 at risk

Group	Value	95% CI
Mupirocin (Treatment)	71
No Mupirocin (Control)	66

Day 9-15 with clinical non-SA infection

Group	Value	95% CI
Mupirocin (Treatment)	0
No Mupirocin (Control)	0

Day 9-15 censored

Group	Value	95% CI
Mupirocin (Treatment)	11
No Mupirocin (Control)	12

Day 16-22 at risk

Group	Value	95% CI
Mupirocin (Treatment)	60
No Mupirocin (Control)	54

Day 16-22 with clinical non-SA infection

Group	Value	95% CI
Mupirocin (Treatment)	0
No Mupirocin (Control)	0

Relative Risk of Occurrence of Non-SA Clinical Infection in the Treatment Compared to Control Group in the According to Protocol Cohort. Secondary · Day 1 through 85

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 identifia

Day 1-8 at risk

Group	Value	95% CI
Mupirocin (Treatment)	67
No Mupirocin (Control)	66

Day 1-8 with clinical non-SA infection

Group	Value	95% CI
Mupirocin (Treatment)	3
No Mupirocin (Control)	1

Day 1-8 censored

Group	Value	95% CI
Mupirocin (Treatment)	3
No Mupirocin (Control)	4

Day 9-15 at Risk

Group	Value	95% CI
Mupirocin (Treatment)	61
No Mupirocin (Control)	61

Day 9-15 with clinical non-SA infection

Group	Value	95% CI
Mupirocin (Treatment)	0
No Mupirocin (Control)	0

Day 9-15 censored

Group	Value	95% CI
Mupirocin (Treatment)	9
No Mupirocin (Control)	11

Day 16-22 at risk

Group	Value	95% CI
Mupirocin (Treatment)	52
No Mupirocin (Control)	50

Day 16-22 with non-SA infection

Group	Value	95% CI
Mupirocin (Treatment)	0
No Mupirocin (Control)	0

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. Secondary · 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 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

Day 1-8 at risk

Group	Value	95% CI
Mupirocin (Treatment)	78
No Mupirocin (Control)	73

Day 1-8 with clinical SA infection

Group	Value	95% CI
Mupirocin (Treatment)	0
No Mupirocin (Control)	2

Day 1-8 censored

Group	Value	95% CI
Mupirocin (Treatment)	5
No Mupirocin (Control)	6

Day 9-15 at risk

Group	Value	95% CI
Mupirocin (Treatment)	73
No Mupirocin (Control)	65

Day 9-15 with clinical SA infection

Group	Value	95% CI
Mupirocin (Treatment)	1
No Mupirocin (Control)	1

Day 9-15 censored

Group	Value	95% CI
Mupirocin (Treatment)	11
No Mupirocin (Control)	12

Day 16-22 at risk

Group	Value	95% CI
Mupirocin (Treatment)	61
No Mupirocin (Control)	52

Day 16-22 with clinical SA infection

Group	Value	95% CI
Mupirocin (Treatment)	0
No Mupirocin (Control)	1

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. Secondary · 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 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 a

Day 1-8 at risk

Group	Value	95% CI
Mupirocin (Treatment)	67
No Mupirocin (Control)	66

Day 1-8 with clinical SA infection

Group	Value	95% CI
Mupirocin (Treatment)	0
No Mupirocin (Control)	2

Day 1-8 censored

Group	Value	95% CI
Mupirocin (Treatment)	4
No Mupirocin (Control)	4

Day 9-15 at risk

Group	Value	95% CI
Mupirocin (Treatment)	63
No Mupirocin (Control)	60

Day 9-15 with clinical SA infection

Group	Value	95% CI
Mupirocin (Treatment)	1
No Mupirocin (Control)	1

Day 9-15 censored

Group	Value	95% CI
Mupirocin (Treatment)	9
No Mupirocin (Control)	11

Day 16-22 at risk

Group	Value	95% CI
Mupirocin (Treatment)	53
No Mupirocin (Control)	48

Day 16-22 with clinical SA infection

Group	Value	95% CI
Mupirocin (Treatment)	0
No Mupirocin (Control)	1

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). Secondary · Day 1 through 85

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

Day 1-8 at risk

Group	Value	95% CI
Mupirocin (Treatment)	66
No Mupirocin (Control)	64

Day 1-8 with decolonization

Group	Value	95% CI
Mupirocin (Treatment)	59
No Mupirocin (Control)	3

Day 1-8 censored

Group	Value	95% CI
Mupirocin (Treatment)	1
No Mupirocin (Control)	14

Day 9-15 at risk

Group	Value	95% CI
Mupirocin (Treatment)	6
No Mupirocin (Control)	47

Day 9-15 with decolonization

Group	Value	95% CI
Mupirocin (Treatment)	3
No Mupirocin (Control)	0

Day 9-15 censored

Group	Value	95% CI
Mupirocin (Treatment)	0
No Mupirocin (Control)	4

Day 16-22 at risk

Group	Value	95% CI
Mupirocin (Treatment)	3
No Mupirocin (Control)	43

Day 16-22 with decolonization

Group	Value	95% CI
Mupirocin (Treatment)	0
No Mupirocin (Control)	0

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. Secondary · Day 1 through 85

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

Day 1-8 at risk

Group	Value	95% CI
Mupirocin (Treatment)	64
No Mupirocin (Control)	63

Day 1-8 with decolonization

Group	Value	95% CI
Mupirocin (Treatment)	57
No Mupirocin (Control)	2

Day 1-8 censored

Group	Value	95% CI
Mupirocin (Treatment)	1
No Mupirocin (Control)	14

Day 9-15 at risk

Group	Value	95% CI
Mupirocin (Treatment)	6
No Mupirocin (Control)	47

Day 9-15 with decolonization

Group	Value	95% CI
Mupirocin (Treatment)	3
No Mupirocin (Control)	0

Day 9-15 censored

Group	Value	95% CI
Mupirocin (Treatment)	0
No Mupirocin (Control)	4

Day 16-22 at risk

Group	Value	95% CI
Mupirocin (Treatment)	3
No Mupirocin (Control)	43

Day 16-22 with decolonization

Group	Value	95% CI
Mupirocin (Treatment)	0
No Mupirocin (Control)	0

Adverse events — posted to ClinicalTrials.gov

Time frame: Adverse events were collected on days 1-7.. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Mupirocin (Treatment)

Serious: 3/80 (4%)

Deaths: —

No Mupirocin (Control)

Serious: 0/75 (0%)

Deaths: —

Serious adverse events (4 terms)

Reaction	System	Mupirocin (Treatment)	No Mupirocin (Control)
Staphylococcal bacteraemia	Infections and infestations	—	—
Heart disease congenital	Congenital, familial and genetic disorders	—	—
Incarcerated inguinal hernia	Gastrointestinal disorders	—	—
Infantile apnoea	Respiratory, thoracic and mediastinal disorders	—	—

Other adverse events (5 terms — click to expand)

Reaction	System	Mupirocin (Treatment)	No Mupirocin (Control)
Apnea	Respiratory, thoracic and mediastinal disorders	—	—
Rash	Skin and subcutaneous tissue disorders	—	—
Application site pain	General disorders	—	—
Diarrhoea	Gastrointestinal disorders	—	—
Administration related reaction	Injury, poisoning and procedural complications	—	—

Most-reported serious reactions: Staphylococcal bacteraemia, Heart disease congenital, Incarcerated inguinal hernia, Infantile apnoea.

Data from ClinicalTrials.gov NCT01827358 adverse events section.

Sponsor's own description

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.

Publications & conference data

3 peer-reviewed publications reference this trial (live from Europe PMC):

1. Mupirocin for <i>Staphylococcus aureus</i> Decolonization of Infants in Neonatal Intensive Care Units.
   Kotloff KL, Shirley DT, Creech CB, Frey SE, et al · · 2019 · cited 25× · PMID 30587533 · DOI 10.1542/peds.2018-1565
2. One size does not fit all: why universal decolonization strategies to prevent methicillin-resistant Staphylococcus aureus colonization and infection in adult intensive care units may be inappropriate for neonatal intensive care units.
   Nelson MU, Bizzarro MJ, Dembry LM, Baltimore RS, et al · · 2014 · cited 23× · PMID 25010223 · DOI 10.1038/jp.2014.125
3. Necrotizing Enterocolitis: What's New and What's Next?
   Sha C, Sander WR, Bass K, Hsieh H, et al · · 2025 · cited 1× · PMID 41096926 · DOI 10.3390/ijms26199660