Safety, Tolerability, and Efficacy of Caspofungin Versus Amphotericin B Deoxycholate in the Treatment of Invasive Candidiasis in Neonates and Infants (MK-0991-064)
Primary Purpose
Candidiasis, Invasive
Status
Terminated
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
Caspofungin
Amphotericin B Deoxycholate
Sponsored by
About this trial
This is an interventional treatment trial for Candidiasis, Invasive
Eligibility Criteria
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
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
Caspofungin
Amphotericin B Deoxycholate
Arm Description
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
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
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
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.
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.
Full Information
NCT ID
NCT01945281
First Posted
September 13, 2013
Last Updated
November 13, 2019
Sponsor
Merck Sharp & Dohme LLC
1. Study Identification
Unique Protocol Identification Number
NCT01945281
Brief Title
Safety, Tolerability, and Efficacy of Caspofungin Versus Amphotericin B Deoxycholate in the Treatment of Invasive Candidiasis in Neonates and Infants (MK-0991-064)
Official Title
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
Study Type
Interventional
2. Study Status
Record Verification Date
November 2019
Overall Recruitment Status
Terminated
Why Stopped
Operational feasibility with low recruitment due to changing epidemiology of disease
Study Start Date
January 15, 2014 (Actual)
Primary Completion Date
January 2, 2018 (Actual)
Study Completion Date
February 28, 2018 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Merck Sharp & Dohme LLC
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Candidiasis, Invasive
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
51 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Caspofungin
Arm Type
Experimental
Arm Description
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
Arm Title
Amphotericin B Deoxycholate
Arm Type
Active Comparator
Arm Description
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
Intervention Type
Drug
Intervention Name(s)
Caspofungin
Intervention Type
Drug
Intervention Name(s)
Amphotericin B Deoxycholate
Primary Outcome Measure Information:
Title
Percentage of Participants With Fungal-free Survival Through the 2-week Post-therapy Period
Description
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.
Time Frame
Up to 104 days
Secondary Outcome Measure Information:
Title
Percentage of Participants With Fungal-free Survival Through the End of Study Treatment
Description
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.
Time Frame
Up to 90 days
Title
Number of Participants With an Adverse Event (AE)
Description
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.
Time Frame
8 weeks after end of study therapy (up to 146 days)
10. Eligibility
Sex
All
Maximum Age & Unit of Time
3 Months
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Medical Director
Organizational Affiliation
Merck Sharp & Dohme LLC
Official's Role
Study Director
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
IPD Sharing URL
http://engagezone.msd.com/ds_documentation.php
Citations:
PubMed Identifier
31586424
Citation
Kim J, Nakwa FL, Araujo Motta F, Liu H, Dorr MB, Anderson LJ, Kartsonis N. A randomized, double-blind trial investigating the efficacy of caspofungin versus amphotericin B deoxycholate in the treatment of invasive candidiasis in neonates and infants younger than 3 months of age. J Antimicrob Chemother. 2020 Jan 1;75(1):215-220. doi: 10.1093/jac/dkz398.
Results Reference
result
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Safety, Tolerability, and Efficacy of Caspofungin Versus Amphotericin B Deoxycholate in the Treatment of Invasive Candidiasis in Neonates and Infants (MK-0991-064)
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