Randomized Study of Caspofungin Prophylaxis Followed by Pre-emptive Therapy for Invasive Candidiasis in the Intensive Care Unit (ICU)

Study Overview
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Brief Summary
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Adults admitted to intensive care units are at risk for a variety of complications. Infections due to the fungus called candida are of particular concern. The study will test the possibility that caspofungin, a new therapy for fungal infections, can successfully reduce the rate of candida infections in subjects at risk. It will also test if caspofungin is useful in treating subjects for this disease when diagnosed using a new blood test that is performed twice weekly, permitting earlier diagnosis than current practice standards.

Official Title
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A Randomized, Double-blind, Placebo Controlled Trial of Caspofungin Prophylaxis Followed by Pre-emptive Therapy for Invasive Candidiasis in High-risk Adults in the Critical Care Setting

Conditions
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Invasive Candidiasis

Intervention / Treatment
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* Drug: Caspofungin
* Drug: Normal Saline


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Non-pregnant >18 yrs of age Subjects admitted to ICU during the preceding 3 days and expected to stay in the ICU for at least another 48 hours.Subjects can be enrolled on days 3-5 of ICU admission. Subjects meeting the clinical prediction rule Exclusion Criteria: Subjects with an allergy/intolerance to caspofungin or echinocandin analog absolute neutrophil count <500/mm3 at study entry or likely to develop such a count during therapy acquired immunodeficiency syndrome, aplastic anemia or chronic granulomatous disease moderate or severe hepatic insufficiency subjects who are pregnant or lactating unlikely to survive < 24 hours subjects who have received systemic antifungal therapy within 10 days prior to study entry Documented active proven or probable invasive fungal infection upon enrollment previously enrolled in this study Currently on another investigational agent or have received an investigational agent within 10 days prior to study entry.

Ages Eligible for Study
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Minimum Age: 18 Years

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: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 1 prophylaxis<br>Caspofungin 50 mg Intravenous (IV) daily up to 28 days of therapy | Drug: Caspofungin<br>* 50 mg IV daily<br>|
| Placebo Comparator: 2 placebo<br>Normal Saline 100 cc IV daily | Drug: Normal Saline<br>* 100 cc IV daily<br>* Other names: placebo;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proven and Probable Invasive Candidiasis Based on Modified Mycoses Study Group/European Organization for Research and Treatment of Cancer (MSG/EORTC) Criteria. | Modified MSG/EORTC criteria for the diagnosis of fungal infections: Proven invasive candidiasis is defined as candidemia, Candida cultured from a sterile site, or histopathological evidence of candida infection. Probable invasive candidiasis is defined as 2 consecutive positive beta glucan levels in the presence of signs and symptoms of infection. | Within 7 days after end of therapy | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Proven Invasive Candidiasis by MSG/ EORTC Criteria. |  | Within 7 days of end of therapy | 
| All Cause Mortality |  | Within 7 days of end of therapy | 
| Initiation of Other Antifungals |  | Within 7 days after end of therapy | 
| Time to Development of Proven or Probable Invasive Candidiasis |  | Within 7 days after end of therapy | 
| Incidence of Proven and Probable Invasive Fungal Infections Other Than Invasive Candidiasis. |  | Within 7 days after end of therapy | 
| Time to Beta Glucan Negativity in Pre-emptive Phase. |  | Within 14 days after end of therapy | 
| Incidence of Complete and Partial Response by Clinical and Microbiological or Serological Evidence for Subjects on the Pre-emptive Therapy Phase. |  | Within 14 days after end of therapy | 
| Hospital Metrics (to be Evaluated Separately for Prophylaxis and Pre-emptive Therapy Phases); Length of Stay in the Hospital, Length of Stay in the ICU, and the Costs Data for the ICU Stay and the Hospitalization, if Available. |  | Hospital discharge | 
| Subjects Who Discontinue Study Therapy Due to a Drug-related Adverse Event |  | Up to 14 days after end of therapy | 
| Subjects With 1 or More Serious Drug-related Adverse Event(s) |  | Up to 14 days after end of therapy | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Candida, Prophylaxis, High risk adults, Intensive care unit (ICU)