Pilot Feasibility Study With Patients Who Are at High Risk For Developing Invasive Candidiasis in a Critical Care Setting (MK-0991-067)

Study Overview
=================
Brief Summary
-----------------
This is a pilot feasibility study that investigates antifungal therapy with caspofungin in patients at high-risk for developing invasive candidiasis in a critical care setting.

Detailed Description
-----------------
Hypothesis: In high-risk non-neutropenic participants in the ICU, the proportion of participants discontinued from study therapy in order to be empirically treated with antifungal therapy for suspected candidiasis outside of the context of this protocol is less than 20% (i.e., the upper bound of the 95% confidence interval for the observed proportion is less than 20%).

Official Title
-----------------
MSG-04 (Also Known as Merck Caspofungin Protocol 067): A Pilot, Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial of Caspofungin Empirical Therapy for Invasive Candidiasis in High-Risk Patients in the Critical Care Setting

Conditions
-----------------
Invasive Candidiasis

Intervention / Treatment
-----------------
* Drug: Caspofungin acetate
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Hospitalization for a minimum of 3 days in an ICU and expectation to stay in the ICU for at least another 48 hours Meets the following high-risk criteria: Requires mechanical ventilation at the time of study entry; and has a central venous catheter in place at the time of study entry; and is receiving broad spectrum antibiotics at the time of study entry; AND meets at least one of the following criteria: Required parenteral nutrition during the current ICU admission; or required renal dialysis during the current ICU admission; or had major surgery during or within the 7 days before the current ICU admission; or was diagnosed with pancreatitis during or within the 7 days before the current ICU admission; or required systemic steroids or other immunosuppressive agents during or within the 7 days before the current ICU admission Meets at least one of the following criteria of suspected infection at the time of study entry or within the 24 hours before study entry: Temperature ≥38° C or ≤36° C (oral equivalent); or hypotension (systolic blood pressure of <90 mm Hg) or significant drop in blood pressure (40 mm Hg) from the participant's normal baseline; or elevated white blood cell count of ≥12,000/mm^3 Candida is growing in at least one non-sterile culture site collected during the current ICU admission Female of childbearing potential has a negative serum or urine pregnancy test before enrollment Exclusion Criteria: Females pregnant or breast feeding History of allergy, hypersensitivity, or any serious reaction to caspofungin or another member of the echinocandin class (e.g., micafungin, anidulafungin) Neutropenia or expected to develop neutropenia during study therapy Diagnosis of acquired immune deficiency syndrome (AIDS), aplastic anemia, or chronic granulomatous disease Diagnosis of moderate or severe hepatic insufficiency Patient not expected to survive at least 24 hours Received systemic (IV or oral) antifungal therapy within 10 days before study entry Active diagnosis of proven or probable invasive fungal infection (IFI) Currently on or has received an investigational agent within 10 days before study entry Any condition or concomitant illness which might confuse the study results or pose additional risk in administering the study therapy

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

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 acetate | Drug: Caspofungin acetate<br>* 70 mg of caspofungin administered intravenously (IV) on Day 1 followed by 50 mg daily for at least 6 additional days (maximum duration study therapy is 14 days)<br>* Other names: Cancidas®;|
| Placebo Comparator: Placebo<br>normal saline | Drug: Placebo<br>* Placebo to caspofungin (normal saline) on Day 1 followed by placebo daily for at least 6 additional days (maximum duration study therapy is 14 days)<br>* Other names: normal saline;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Proportion of Patients Discontinued From Study Therapy to be Treated With Empirical Antifungal Therapy Outside of the Context of the Study. | The feasibility of conducting a major randomized study of caspofungin for empirical therapy for invasive candidiasis in high-risk non-neutropenic intensive care unit (ICU) participants was to be assessed by the incidence of study therapy discontinuations due to investigators choosing to treat participants with empirical antifungal therapy outside of the context of this protocol. Study drug was administered for a minimum of 7 days to a maximum of 14 days provided participants had no evidence of confirmed breakthrough invasive Candida infection while receiving study drug. | 1 to 14 days | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Invasive Candidiasis, Fungal Infection, Empirical Therapy, Candidiasis