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

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

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.

Study Overview

• Status: Terminated
• Conditions: Candidiasis, Invasive
• Intervention / Treatment: Drug: Caspofungin; Drug: Amphotericin B Deoxycholate

• Study Type: Interventional
• Enrollment (Actual): 51
• Phase: Phase 2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 3 months (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Caspofungin; 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
Active Comparator: Amphotericin B Deoxycholate; 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

What is the study measuring?

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)

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): January 15, 2014
• Primary Completion (Actual): January 2, 2018
• Study Completion (Actual): February 28, 2018

Study Registration Dates

• First Submitted: September 13, 2013
• First Submitted That Met QC Criteria: September 13, 2013
• First Posted (Estimate): September 18, 2013

Study Record Updates

• Last Update Posted (Actual): November 25, 2019
• Last Update Submitted That Met QC Criteria: November 13, 2019
• Last Verified: November 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; Bacterial Infections and Mycoses; Mycoses; Invasive Fungal Infections; Candidiasis; Candidiasis, Invasive; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Gastrointestinal Agents; Anti-Bacterial Agents; Antifungal Agents; Antiprotozoal Agents; Antiparasitic Agents; Amebicides; Cholagogues and Choleretics; Caspofungin; Deoxycholic Acid; Amphotericin B; Liposomal amphotericin B; Amphotericin B, deoxycholate drug combination
• Other Study ID Numbers: 0991-064; 2013-002084-26 (EudraCT Number); MK-0991-064 (Other Identifier: Merck Protocol Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf