Trial Outcomes & Findings for Prospective Two-Year Study to Assess Miconazole Nitrate Resistance in Neonates and Infants (NCT NCT00702507)

NCT ID: NCT00702507

Last Updated: 2012-03-27

Results Overview

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.

• Recruitment status: COMPLETED
• Study phase: PHASE4
• Target enrollment: 200 participants
• Primary outcome timeframe: Test-of-cure visit (Day 14) of initial treatment episode
• Results posted on: 2012-03-27

Participant Flow

The study consisted of 2 phases: initial treatment phase (14-day study period) and a follow-up phase (2-year study period).

Participant milestones

Measure	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.
Initial Treatment Phase STARTED	200
Initial Treatment Phase COMPLETED	159
Initial Treatment Phase NOT COMPLETED	41
Follow-up Phase STARTED	159
Follow-up Phase COMPLETED	132
Follow-up Phase NOT COMPLETED	27

Reasons for withdrawal

Measure	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.
Initial Treatment Phase Adverse Event	2
Initial Treatment Phase Participant's Caretaker Withdrew Consent	3
Initial Treatment Phase Lost to Follow-up	2
Initial Treatment Phase Negative Candida Culture	34
Follow-up Phase Participant's Caretaker Withdrew Consent	1
Follow-up Phase Protocol Violation	2
Follow-up Phase Lost to Follow-up	23
Follow-up Phase Late Enrollment	1

Baseline Characteristics

Prospective Two-Year Study to Assess Miconazole Nitrate Resistance in Neonates and Infants

Baseline characteristics by cohort

Measure	Vusion Treatment n=200 Participants 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.
Age Continuous	6.6 Months STANDARD_DEVIATION 3.80 • n=5 Participants
Sex: Female, Male Female	112 Participants n=5 Participants
Sex: Female, Male Male	88 Participants n=5 Participants
Race/Ethnicity, Customized White	40 participants n=5 Participants
Race/Ethnicity, Customized Black	17 participants n=5 Participants
Race/Ethnicity, Customized Hispanic/Latino	121 participants n=5 Participants
Race/Ethnicity, Customized Hispanic/Persian	1 participants n=5 Participants
Race/Ethnicity, Customized Hispanic/White	5 participants n=5 Participants
Race/Ethnicity, Customized White/Black	1 participants n=5 Participants
Race/Ethnicity, Customized Multiracial	15 participants n=5 Participants

PRIMARY outcome

Timeframe: 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)

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.

Outcome measures

Measure	Vusion Treatment n=168 Participants 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 DDCC during the 2-year follow-up period, the participant was treated for 7 days with Vusion ointment.
Number of Participants With Overall Cure (OC) Success	49 participants
Number of Participants With Overall Cure (OC) Failure	119 participants

SECONDARY outcome

Timeframe: Test-of-cure visit (Day 14) of initial treatment episode

Population: MITT Population

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.

Outcome measures

Measure	Vusion Treatment n=168 Participants 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 DDCC during the 2-year follow-up period, the participant was treated for 7 days with Vusion ointment.
Number of Participants With Clinical Cure Failure	85 participants
Number of Participants With Clinical Cure Success	83 participants

SECONDARY outcome

Timeframe: Test-of-cure visit (Day 14) of initial treatment episode

Population: MITT Population

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.

Outcome measures

Measure	Vusion Treatment n=168 Participants 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 DDCC during the 2-year follow-up period, the participant was treated for 7 days with Vusion ointment.
Number of Participants With Mycological Cure Success	77 participants
Number of Participants With Mycological Cure Failure	91 participants

SECONDARY outcome

Timeframe: Test-of-cure visit (Day 14) of initial treatment episode

Population: MITT Population. Participants with missing data were not included in this analysis.

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).

Outcome measures

Measure	Vusion Treatment n=160 Participants 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 DDCC during the 2-year follow-up period, the participant was treated for 7 days with Vusion ointment.
Clinical Evaluations Using the Diaper Dermatitis Severity Index Score for Initial Treatment Episode	0.0 scores on a scale Interval 0.0 to 7.0

SECONDARY outcome

Timeframe: Test-of-cure visit (Day 14) of initial treatment episode

Population: MITT Population. Participants with missing data were not included in this analysis.

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).

Outcome measures

Measure	Vusion Treatment n=160 Participants 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 DDCC during the 2-year follow-up period, the participant was treated for 7 days with Vusion ointment.
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 Interval -8.0 to 1.0

SECONDARY outcome

Timeframe: 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

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.

Outcome measures

Measure	Vusion Treatment n=35 Participants 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 DDCC during the 2-year follow-up period, the participant was treated for 7 days with Vusion ointment.
Number of Participants With Overall Cure (OC) of First to Third Recurrent Episodes (RE) First Recurrence, Success; n=35	11 participants
Number of Participants With Overall Cure (OC) of First to Third Recurrent Episodes (RE) Third Recurrence, Success; n=4	2 participants
Number of Participants With Overall Cure (OC) of First to Third Recurrent Episodes (RE) First Recurrence, Failure; n=35	24 participants
Number of Participants With Overall Cure (OC) of First to Third Recurrent Episodes (RE) Second Recurrence, Success; n=10	5 participants
Number of Participants With Overall Cure (OC) of First to Third Recurrent Episodes (RE) Second Recurrence, Failure; n=10	5 participants
Number of Participants With Overall Cure (OC) of First to Third Recurrent Episodes (RE) Third Recurrence Failure; n=4	2 participants

SECONDARY outcome

Timeframe: 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

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.

Outcome measures

Measure	Vusion Treatment n=35 Participants 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 DDCC during the 2-year follow-up period, the participant was treated for 7 days with Vusion ointment.
Number of Participants With Clinical Cure of First to Third Recurrent Episodes Third Recurrence, Success; n=4	3 participants
Number of Participants With Clinical Cure of First to Third Recurrent Episodes First Recurrence, Success; n=35	20 participants
Number of Participants With Clinical Cure of First to Third Recurrent Episodes First Recurrence, Failure; n=35	15 participants
Number of Participants With Clinical Cure of First to Third Recurrent Episodes Second Recurrence, Success; n=10	5 participants
Number of Participants With Clinical Cure of First to Third Recurrent Episodes Second Recurrence, Failure; n=10	5 participants
Number of Participants With Clinical Cure of First to Third Recurrent Episodes Third Recurrence Failure; n=4	1 participants

SECONDARY outcome

Timeframe: 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

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.

Outcome measures

Measure	Vusion Treatment n=35 Participants 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 DDCC during the 2-year follow-up period, the participant was treated for 7 days with Vusion ointment.
Number of Participants With Mycological Cure of First to Third Recurrent Episodes First Recurrence, Success; n=35	16 participants
Number of Participants With Mycological Cure of First to Third Recurrent Episodes First Recurrence, Failure; n=35	19 participants
Number of Participants With Mycological Cure of First to Third Recurrent Episodes Second Recurrence, Success; n=10	7 participants
Number of Participants With Mycological Cure of First to Third Recurrent Episodes Second Recurrence, Failure; n=10	3 participants
Number of Participants With Mycological Cure of First to Third Recurrent Episodes Third Recurrence, Success; n=4	3 participants
Number of Participants With Mycological Cure of First to Third Recurrent Episodes Third Recurrence Failure; n=4	1 participants

Adverse Events

Vusion Initial Treatment Phase

Serious events: 0 serious events

Other events: 42 other events

Deaths: 0 deaths

Vusion Follow-up Phase

Serious events: 3 serious events

Other events: 133 other events

Deaths: 0 deaths

Serious adverse events

Measure	Vusion Initial Treatment Phase n=200 participants at risk 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.	Vusion Follow-up Phase n=168 participants at risk After the Initial Treatment Phase 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 containing 0.25 percent miconazole nitrate.
Nervous system disorders Febrile Convulsion	0.00% 0/200	0.60% 1/168
Infections and infestations Staphylococcal Infection	0.00% 0/200	0.60% 1/168
Infections and infestations Pneumonia	0.00% 0/200	0.60% 1/168

Other adverse events

Measure	Vusion Initial Treatment Phase n=200 participants at risk 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.	Vusion Follow-up Phase n=168 participants at risk After the Initial Treatment Phase 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 containing 0.25 percent miconazole nitrate.
Infections and infestations Varicella	0.00% 0/200	3.6% 6/168
Infections and infestations Viral infection	0.50% 1/200	6.0% 10/168
Infections and infestations Viral rash	1.5% 3/200	4.2% 7/168
Injury, poisoning and procedural complications Arthropod bite	0.00% 0/200	3.6% 6/168
Respiratory, thoracic and mediastinal disorders Asthma	0.50% 1/200	9.5% 16/168
Respiratory, thoracic and mediastinal disorders Cough	0.50% 1/200	15.5% 26/168
Respiratory, thoracic and mediastinal disorders Rhinitis allergic	0.00% 0/200	3.6% 6/168
Skin and subcutaneous tissue disorders Dermatitis diaper	0.00% 0/200	13.7% 23/168
Eye disorders Conjunctivitis	0.50% 1/200	7.1% 12/168
Gastrointestinal disorders Diarrhoea	4.0% 8/200	24.4% 41/168
Gastrointestinal disorders Vomiting	1.5% 3/200	13.1% 22/168
General disorders Pyrexia	9.0% 18/200	47.0% 79/168
Infections and infestations Amoebiasis	0.00% 0/200	4.8% 8/168
Infections and infestations Bronchitis	0.50% 1/200	6.5% 11/168
Infections and infestations Diarrhoea infectious	0.00% 0/200	5.4% 9/168
Infections and infestations Ear infection	1.0% 2/200	6.5% 11/168
Infections and infestations Impetigo	1.0% 2/200	4.8% 8/168
Infections and infestations Influenza	1.0% 2/200	4.2% 7/168
Infections and infestations Nasopharyngitis	9.5% 19/200	41.1% 69/168
Infections and infestations Otitis media acute	1.0% 2/200	7.7% 13/168
Infections and infestations Pharyngitis	0.00% 0/200	7.1% 12/168
Infections and infestations Pharyngotonsilitis	0.00% 0/200	8.9% 15/168
Infections and infestations Respiratory tract infection	0.00% 0/200	6.0% 10/168
Infections and infestations Rhinitis	1.0% 2/200	8.3% 14/168
Infections and infestations Tonsillitis	0.50% 1/200	16.7% 28/168

Additional Information

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Phone: 866-435-7343

Results disclosure agreements

• Principal investigator is a sponsor employee GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.
• Publication restrictions are in place

Restriction type: OTHER