Safety, Tolerability, and Efficacy of Caspofungin Versus Amphotericin B Deoxycholate in the Treatment of Invasive Candidiasis in Neonates and Infants (MK-0991-064)

Study Overview
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Brief Summary
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The study will evaluate the safety, tolerability, and efficacy of caspofungin as compared with amphotericin B deoxycholate in the treatment of invasive candidiasis in neonates and infants. The primary hypothesis to be tested in the study is that caspofungin will be superior to amphotericin B deoxycholate with regard to the proportion of participants with fungal-free survival at the 2-week post-therapy follow-up visit.

Official Title
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A Multicenter, Double-Blind, Randomized, Comparator-Controlled Study to Evaluate the Safety, Tolerability, and Efficacy of Caspofungin Versus Amphotericin B Deoxycholate in the Treatment of Invasive Candidiasis in Neonates and Infants Less Than 3 Months of Age

Conditions
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Candidiasis, Invasive

Intervention / Treatment
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* Drug: Caspofungin
* Drug: Amphotericin B Deoxycholate


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Culture-confirmed invasive Candida infection Exclusion Criteria: Candida disease limited to the oropharynx, esophagus, or other mucosal or superficial skin surfaces Positive culture for Candida only from sputum, broncho-alveolar lavage, catheter tip, or previously placed indwelling non-vascular catheters or drains Prosthetic device as the suspected site of Candida infection Active co-infection with a non-Candida fungal organism Received >48 hours of systemic antifungal treatment since the positive Candida index culture was collected as therapy for the present episode of invasive candidiasis Failed prior systemic antifungal therapy for the present episode of invasive candidiasis Diagnosis of acute hepatitis or cirrhosis Scheduled or anticipated to receive rifampin or other systemic antifungal therapy while on study therapy History (including participant's mother) of allergy, hypersensitivity, or any serious reaction to caspofungin or other member of the echinocandin class, or to amphotericin B deoxycholate or other member of the polyene class Severe congenital disorder known to lower immune response

Ages Eligible for Study
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Maximum Age: 3 Months

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Caspofungin<br>Caspofungin 2 mg/kg intravenous once daily for ≥14 days after documented negative culture and improvement of clinical signs and symptoms, for a maximum of 90 days treatment | Drug: Caspofungin<br> <br> |
| Active Comparator: Amphotericin B Deoxycholate<br>Amphotericin B deoxycholate 1 mg/kg intravenous once daily for ≥14 days after documented negative culture and improvement of clinical signs and symptoms, for a maximum of 90 days treatment | Drug: Amphotericin B Deoxycholate<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Fungal-free Survival Through the 2-week Post-therapy Period | Fungal-free survival is those participants who survived up to 2 weeks post-therapy, and had documented microbiological eradication of Candida species (sp.) from follow-up cultures collected after the initiation of study therapy. Microbiological eradication denotes negative follow-up cultures for Candida sp. from the site of infection. If a culture is not obtained on the day of assessment, the last culture after study entry may be used to assist in the assessment of microbiological eradication. If the last culture is negative for Candida sp., then microbiological eradication would be considered achieved. | Up to 104 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Fungal-free Survival Through the End of Study Treatment | Fungal-free survival is those participants who survived up to end of study treatment, and had documented microbiological eradication of Candida sp. from follow-up cultures collected after the initiation of study therapy. Microbiological eradication denotes negative follow-up cultures for Candida sp. from the site of infection. If a culture is not obtained on the day of assessment, the last culture after study entry may be used to assist in the assessment of microbiological eradication. If the last culture is negative for Candida sp., then microbiological eradication would be considered achieved. | Up to 90 days | 
| Number of Participants With an Adverse Event (AE) | An AE is any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the SPONSOR's product, whether or not considered related to the use of the product. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition which is temporally associated with the use of the SPONSOR's product, is also an AE. | 8 weeks after end of study therapy (up to 146 days) |