Diaper Rash
Conditions
Keywords
Diaper dermatitis complicated by candidiasis
Brief summary
The purpose of this study is to determine whether repeated use of 0.25% miconazole nitrate ointment in newborns and infants with a yeast infection in the diaper area causes the yeast to become resistant to the drug.
Detailed description
The objective of this study is to investigate the potential for the development of resistance in Candida spp. after repeated treatment courses of 0.25% miconazole nitrate ointment in neonates and infants up to one year of age.
Interventions
DRUG0.25 % Miconazole Nitrate Ointment
Topical Application
Sponsors
GlaxoSmithKline
Stiefel, a GSK Company
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
No minimum to 15 Months
Healthy volunteers
No
Inclusion criteria
* Male or female neonate or infant up to 1 year of age with Fitzpatrick Skin Type I-VI * Clinical evidence of diaper dermatitis and a positive KOH result for pseudohyphae and/or budding yeast at baseline visit * Overall Diaper Dermatitis Severity Index score at baseline visit of 4-8 (must include an overall clinical grade of at least 2 for erythema) * Wear commercially available diapers day and night for at least 7 days prior to enrollment and during the course of the 2 year study * Caretaker must complete informed consent process
Exclusion criteria
* Known sensitivity to any component of the formulation * No other skin conditions that may confound the evaluation of the drug efficacy or tolerability * Known sensitivity to skin care toiletry products or diapers * History of HIV positive * Chronic illnesses that require systemic medication that may confound the evaluation of study drug efficacy or tolerability (antibiotic therapy is not included) * Treatment with a prescription product for diaper dermatitis or other skin condition 7 days prior to enrollment
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Overall Cure (OC) | Test-of-cure visit (Day 14) of initial treatment episode | OC was defined as both clinical (therapeutic) cure with total resolution of signs/symptoms (no clinical signs of infection) and microbiological cure with mycological eradication (both negative potassium hydroxide \[KOH\] and culture results). Participants who had OC were categorized as Successes; those without OC were categorized as Failures. Any discontinued or lost to follow-up participant was also considered a failure. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Mycological Cure | Test-of-cure visit (Day 14) of initial treatment episode | Participants were evaluated for mycological cure, which was defined as mycological eradication with negative KOH and culture results. Participants who had mycological cure were categorized as Successes; those without mycological cure were categorized as Failures. Any discontinued or lost to follow-up participant was also considered a failure. |
| Clinical Evaluations Using the Diaper Dermatitis Severity Index Score for Initial Treatment Episode | Test-of-cure visit (Day 14) of initial treatment episode | The diaper dermatitis severity index score was calculated as the sum of severity grades for each parameter evaluated (erythema, papules or pustules, and erosions) for the initial treatment episode. The maximum score possible for the diaper dermatitis severity index is 8. Rating scale for Erythema: 0 (none to trace), 1 (mild \[pink\]), 2 (moderate \[red\]), 3 (severe \[beefy red\]). Rating scale for Papules or Pustules: 0 (none to trace \[0\]), 1 (few \[1-10\]), 2 (multiple \[11-20\]), 3 (many \[21-40\]), 4 (abundant \[more than 40\]. Rating scale for Erosions: 0 (absent), 1 (present). |
| Clinical Evaluations Using Change From Baseline in the Dermatitis Severity Index Score at Day 14 of the Initial Treatment Episode | Test-of-cure visit (Day 14) of initial treatment episode | The diaper dermatitis severity index score was calculated as the sum of severity grades for each parameter evaluated (erythema, papules or pustules, and erosions). Change from baseline=baseline value minus Day 14 value. The maximum score possible for the diaper dermatitis severity index is 8. Rating scale for Erythema: 0 (none to trace), 1 (mild \[pink\]), 2 (moderate \[red\]), 3 (severe \[beefy red\]). Rating scale for Papules or Pustules: 0 (none to trace \[0\]), 1 (few \[1-10\]), 2 (multiple \[11-20\]), 3 (many \[21-40\]), 4 (abundant \[more than 40\]. Rating scale for Erosions: 0 (absent), 1 (present). |
| Number of Participants With Clinical Cure | Test-of-cure visit (Day 14) of initial treatment episode | Participants were evaluated for clinical cure, which was defined as therapeutic cure with total resolution of signs and symptoms (i.e., no clinical signs of infection). Participants who had clinical cure were categorized as Successes; those without clianical cure were categorized as Failures. Any discontinued or lost to follow-up participant was also considered a failure. |
| Number of Participants With Clinical Cure of First to Third Recurrent Episodes | Test-of-cure visit (Day 14) of first to third recurrent episodes (up to approximately 1 year and 7 months) | Participants were evaluated for clinical cure, which was defined as therapeutic cure with total resolution of signs and symptoms (i.e., no clinical signs of infection). Participants who had clinical cure were categorized as Successes; those without clinical cure were categorized as Failures. Any discontinued or lost to follow-up participant was also considered a failure. |
| Number of Participants With Mycological Cure of First to Third Recurrent Episodes | Test-of-cure visit (Day 14) of first to third recurrent episodes (up to approximately 1 year and 7 months) | Participants were evaluated for mycological cure, which was defined as mycological eradication with negative KOH and culture results. Participants who had mycological cure were categorized as Successes; those without mycological cure were categorized as Failures. Any discontinued or lost to follow-up participant was also considered a failure. |
| Number of Participants With Overall Cure (OC) of First to Third Recurrent Episodes (RE) | Test-of-cure (TOC) visit (Day 14) of first to third recurrent episodes (up to approximately 1 year and 7 months) | OC was defined as both clinical (therapeutic) cure with total resolution of signs/symptoms (no clinical signs of infection) and microbiological cure with mycological eradication (both negative potassium hydroxide and culture results) at TOC visit for initial episode (ep.) to third ep. Participants (par) who had OC were categorized as Successes; those without OC were categorized as Failures (discontinued/lost to follow-up par were also failures). A RE is not temporally associated with a prior episode (PE) irrespective of whether the PE involves continuing treatment with study medication. |
Countries
Dominican Republic, Ecuador, Panama, United States
Participant flow
Pre-assignment details
The study consisted of 2 phases: initial treatment phase (14-day study period) and a follow-up phase (2-year study period).
Participants by arm
| Arm | Count |
|---|---|
| Vusion Treatment Participants were treated with Vusion ointment containing 0.25 percent miconazole nitrate for 7 days. A follow-up post-treatment visit was conducted at Study Day 14. Further, participants were followed for 2 years. If there was a recurrent episode of diaper dermatitis complicated by candidiasis (DDCC) during the 2-year follow-up period, the participant was treated for 7 days with Vusion ointment. | 200 |
| Total | 200 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Follow-up Phase | Late Enrollment | 1 |
| Follow-up Phase | Lost to Follow-up | 23 |
| Follow-up Phase | Participant's Caretaker Withdrew Consent | 1 |
| Follow-up Phase | Protocol Violation | 2 |
| Initial Treatment Phase | Adverse Event | 2 |
| Initial Treatment Phase | Lost to Follow-up | 2 |
| Initial Treatment Phase | Negative Candida Culture | 34 |
| Initial Treatment Phase | Participant's Caretaker Withdrew Consent | 3 |
Baseline characteristics
| Characteristic | Vusion Treatment |
|---|---|
| Age Continuous | 6.6 Months STANDARD_DEVIATION 3.8 |
| Race/Ethnicity, Customized Black | 17 participants |
| Race/Ethnicity, Customized Hispanic/Latino | 121 participants |
| Race/Ethnicity, Customized Hispanic/Persian | 1 participants |
| Race/Ethnicity, Customized Hispanic/White | 5 participants |
| Race/Ethnicity, Customized Multiracial | 15 participants |
| Race/Ethnicity, Customized White | 40 participants |
| Race/Ethnicity, Customized White/Black | 1 participants |
| Sex: Female, Male Female | 112 Participants |
| Sex: Female, Male Male | 88 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 42 / 200 | 133 / 168 |
| serious Total, serious adverse events | 0 / 200 | 3 / 168 |
Outcome results
Primary
Number of Participants With Overall Cure (OC)
OC was defined as both clinical (therapeutic) cure with total resolution of signs/symptoms (no clinical signs of infection) and microbiological cure with mycological eradication (both negative potassium hydroxide \[KOH\] and culture results). Participants who had OC were categorized as Successes; those without OC were categorized as Failures. Any discontinued or lost to follow-up participant was also considered a failure.
Time frame: Test-of-cure visit (Day 14) of initial treatment episode
Population: Modified Intent-to-Treat (MITT) Population: all participants who were dispensed study drug and had demonstrated clinical symptoms of diaper dermatitis (DD) (DD severity index score of 4-8; clinical erythema grade of \>=2 \[see outcome measure #4 for a description\]) and confirmed Candida species (positive baseline KOH and culture for Candida species)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Vusion Treatment | Number of Participants With Overall Cure (OC) | Success | 49 participants |
| Vusion Treatment | Number of Participants With Overall Cure (OC) | Failure | 119 participants |
95% CI: [22.4, 36.7]
Secondary
Clinical Evaluations Using Change From Baseline in the Dermatitis Severity Index Score at Day 14 of the Initial Treatment Episode
The diaper dermatitis severity index score was calculated as the sum of severity grades for each parameter evaluated (erythema, papules or pustules, and erosions). Change from baseline=baseline value minus Day 14 value. The maximum score possible for the diaper dermatitis severity index is 8. Rating scale for Erythema: 0 (none to trace), 1 (mild \[pink\]), 2 (moderate \[red\]), 3 (severe \[beefy red\]). Rating scale for Papules or Pustules: 0 (none to trace \[0\]), 1 (few \[1-10\]), 2 (multiple \[11-20\]), 3 (many \[21-40\]), 4 (abundant \[more than 40\]. Rating scale for Erosions: 0 (absent), 1 (present).
Time frame: Test-of-cure visit (Day 14) of initial treatment episode
Population: MITT Population. Participants with missing data were not included in this analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Vusion Treatment | Clinical Evaluations Using Change From Baseline in the Dermatitis Severity Index Score at Day 14 of the Initial Treatment Episode | -5.0 scores on a scale |
Secondary
Clinical Evaluations Using the Diaper Dermatitis Severity Index Score for Initial Treatment Episode
The diaper dermatitis severity index score was calculated as the sum of severity grades for each parameter evaluated (erythema, papules or pustules, and erosions) for the initial treatment episode. The maximum score possible for the diaper dermatitis severity index is 8. Rating scale for Erythema: 0 (none to trace), 1 (mild \[pink\]), 2 (moderate \[red\]), 3 (severe \[beefy red\]). Rating scale for Papules or Pustules: 0 (none to trace \[0\]), 1 (few \[1-10\]), 2 (multiple \[11-20\]), 3 (many \[21-40\]), 4 (abundant \[more than 40\]. Rating scale for Erosions: 0 (absent), 1 (present).
Time frame: Test-of-cure visit (Day 14) of initial treatment episode
Population: MITT Population. Participants with missing data were not included in this analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Vusion Treatment | Clinical Evaluations Using the Diaper Dermatitis Severity Index Score for Initial Treatment Episode | 0.0 scores on a scale |
Secondary
Number of Participants With Clinical Cure
Participants were evaluated for clinical cure, which was defined as therapeutic cure with total resolution of signs and symptoms (i.e., no clinical signs of infection). Participants who had clinical cure were categorized as Successes; those without clianical cure were categorized as Failures. Any discontinued or lost to follow-up participant was also considered a failure.
Time frame: Test-of-cure visit (Day 14) of initial treatment episode
Population: MITT Population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Vusion Treatment | Number of Participants With Clinical Cure | Success | 83 participants |
| Vusion Treatment | Number of Participants With Clinical Cure | Failure | 85 participants |
Secondary
Number of Participants With Clinical Cure of First to Third Recurrent Episodes
Participants were evaluated for clinical cure, which was defined as therapeutic cure with total resolution of signs and symptoms (i.e., no clinical signs of infection). Participants who had clinical cure were categorized as Successes; those without clinical cure were categorized as Failures. Any discontinued or lost to follow-up participant was also considered a failure.
Time frame: Test-of-cure visit (Day 14) of first to third recurrent episodes (up to approximately 1 year and 7 months)
Population: MITT Population: only those participants with confirmed recurrence were analyzed
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Vusion Treatment | Number of Participants With Clinical Cure of First to Third Recurrent Episodes | First Recurrence, Success; n=35 | 20 participants |
| Vusion Treatment | Number of Participants With Clinical Cure of First to Third Recurrent Episodes | First Recurrence, Failure; n=35 | 15 participants |
| Vusion Treatment | Number of Participants With Clinical Cure of First to Third Recurrent Episodes | Second Recurrence, Success; n=10 | 5 participants |
| Vusion Treatment | Number of Participants With Clinical Cure of First to Third Recurrent Episodes | Second Recurrence, Failure; n=10 | 5 participants |
| Vusion Treatment | Number of Participants With Clinical Cure of First to Third Recurrent Episodes | Third Recurrence, Success; n=4 | 3 participants |
| Vusion Treatment | Number of Participants With Clinical Cure of First to Third Recurrent Episodes | Third Recurrence Failure; n=4 | 1 participants |
Secondary
Number of Participants With Mycological Cure
Participants were evaluated for mycological cure, which was defined as mycological eradication with negative KOH and culture results. Participants who had mycological cure were categorized as Successes; those without mycological cure were categorized as Failures. Any discontinued or lost to follow-up participant was also considered a failure.
Time frame: Test-of-cure visit (Day 14) of initial treatment episode
Population: MITT Population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Vusion Treatment | Number of Participants With Mycological Cure | Success | 77 participants |
| Vusion Treatment | Number of Participants With Mycological Cure | Failure | 91 participants |
Secondary
Number of Participants With Mycological Cure of First to Third Recurrent Episodes
Participants were evaluated for mycological cure, which was defined as mycological eradication with negative KOH and culture results. Participants who had mycological cure were categorized as Successes; those without mycological cure were categorized as Failures. Any discontinued or lost to follow-up participant was also considered a failure.
Time frame: Test-of-cure visit (Day 14) of first to third recurrent episodes (up to approximately 1 year and 7 months)
Population: MITT Population: only those participants with confirmed recurrence were analyzed
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Vusion Treatment | Number of Participants With Mycological Cure of First to Third Recurrent Episodes | First Recurrence, Success; n=35 | 16 participants |
| Vusion Treatment | Number of Participants With Mycological Cure of First to Third Recurrent Episodes | First Recurrence, Failure; n=35 | 19 participants |
| Vusion Treatment | Number of Participants With Mycological Cure of First to Third Recurrent Episodes | Second Recurrence, Success; n=10 | 7 participants |
| Vusion Treatment | Number of Participants With Mycological Cure of First to Third Recurrent Episodes | Second Recurrence, Failure; n=10 | 3 participants |
| Vusion Treatment | Number of Participants With Mycological Cure of First to Third Recurrent Episodes | Third Recurrence, Success; n=4 | 3 participants |
| Vusion Treatment | Number of Participants With Mycological Cure of First to Third Recurrent Episodes | Third Recurrence Failure; n=4 | 1 participants |
Secondary
Number of Participants With Overall Cure (OC) of First to Third Recurrent Episodes (RE)
OC was defined as both clinical (therapeutic) cure with total resolution of signs/symptoms (no clinical signs of infection) and microbiological cure with mycological eradication (both negative potassium hydroxide and culture results) at TOC visit for initial episode (ep.) to third ep. Participants (par) who had OC were categorized as Successes; those without OC were categorized as Failures (discontinued/lost to follow-up par were also failures). A RE is not temporally associated with a prior episode (PE) irrespective of whether the PE involves continuing treatment with study medication.
Time frame: Test-of-cure (TOC) visit (Day 14) of first to third recurrent episodes (up to approximately 1 year and 7 months)
Population: MITT Population: only those participants with confirmed recurrence were analyzed
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Vusion Treatment | Number of Participants With Overall Cure (OC) of First to Third Recurrent Episodes (RE) | First Recurrence, Success; n=35 | 11 participants |
| Vusion Treatment | Number of Participants With Overall Cure (OC) of First to Third Recurrent Episodes (RE) | First Recurrence, Failure; n=35 | 24 participants |
| Vusion Treatment | Number of Participants With Overall Cure (OC) of First to Third Recurrent Episodes (RE) | Second Recurrence, Success; n=10 | 5 participants |
| Vusion Treatment | Number of Participants With Overall Cure (OC) of First to Third Recurrent Episodes (RE) | Second Recurrence, Failure; n=10 | 5 participants |
| Vusion Treatment | Number of Participants With Overall Cure (OC) of First to Third Recurrent Episodes (RE) | Third Recurrence, Success; n=4 | 2 participants |
| Vusion Treatment | Number of Participants With Overall Cure (OC) of First to Third Recurrent Episodes (RE) | Third Recurrence Failure; n=4 | 2 participants |