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A PILOT, MULTICENTER, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED TRIAL OF CASPOFUNGIN EMPIRICAL TH

MSG-04 (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

Objective

This is an investigator-initiated pilot feasibility study sponsored by the Mycoses Study Group (MSG) to evaluate the use of antifungal empirical therapy in patients who are at high risk for developing invasive candidiasis in the critical care setting. At the same time, the study will gather information regarding the efficacy endpoints for use of antifungal empirical therapy in patients who are at high risk for developing invasive candidiasis in the critical care setting.  Based on these data, a larger clinical study may be conducted in the future. 

Patients will be randomized to receive either caspofungin IV 70 mg loading dose followed by 50 mg OR placebo 0.9% saline IV daily.  Caspofungin is FDA approved for the treatment of invasive fungal infections but has not been proven to prevent invasive fungal infections.  Patients will be randomized 1:1 to receive either caspofungin or placebo.  Patients will receive treatment for a minimum of 7 days and a maximum of 14 days.  During the course of the study patients will be closely monitored for clinical signs suggestive of fungal infections; samples will be collected for surrogate markers, such as beta glucans, which is a component of the fungal cell wall; surveillance cultures will be collected from 3 non-sterile sites at several time points during the study to check for presences of yeast (colonization).

The principal investigator or the study coordinator will be providing consent.  On occasion, co-investigators Marilyn Levi or Nancy Madinger may assist the study coordinator with providing consent and/or enrolling patients in the event the principal investigator is not available.

Co-investigators: Nancy Madinger, MD; Marilyn Levi, MD; Todd Bull, MD; Robert McIntyre, MD

IRB Protocol Number
10-0660

All Other Trials

  • Infections
Contact
Kris Richardson at 303-266-6584
or kris.richardson@ucdenver.edu
Eligibility and Other Participant Information

Enrollment Goals

Approved for 12 patients total for the duration of study.  The study’s goal is a minimum of one subject/site/per month but encouraged to enroll as many as possible, as it will be competitive enrollment.  Our average enrollment for similar studies has been about one patient per month.

Inclusion Criteria

1. The patient is at least 18 years of age (at the time of screening).

2. The patient has been hospitalized for a minimum of 72 hours in the medical/surgical ICU and is expected to stay in the medical/surgical ICU for at least another 48 hours.  NOTE: The study is designed to enroll patients from medical or surgical ICUs.  Patients admitted with cardiac conditions (e.g., cardiogenic shock) to a cardiac ICU or with severe burns to a burn ICU are not eligible for participation. 

3. The patient fulfills the following high-risk criteria (as defined in the TREAT study [9]):

a)  The patient required mechanical ventilation on Days 1-3 of ICU admission, AND
b) The patient had a central venous catheter in place on Days 1-3 of ICU admission, AND
c) The patient received broad spectrum antibiotics on Days 1-3 of ICU admission, AND
d) The patient fulfills at least 1 of the following 5 criteria: 


  • The patient required the use of parenteral nutrition on Days 1-3 of ICU admission, OR
  • The patient required renal dialysis (either renal replacement therapy or peritoneal dialysis) on Days 1-3 of ICU admission, OR
  • The patient had undergone a major surgery within the 7 days prior to ICU admission, OR
  • The patient was diagnosed with pancreatitis within the 7 days prior to ICU admission, OR,
  • The patient required the use of systemic steroids or the use of other immunosuppressive agents within the 7 days prior to ICU admission.

4.  At the time of screening, the patient fulfills at least 1 of the 3 following criteria of suspected infection:

a)   Temperature > 38ºC or < 36oC (Oral equivalent), OR
b) Hypotension defined as a systolic blood pressure of < 90 mm Hg or a significant drop in blood pressure (40 mm Hg) from the patient’s normal baseline, OR
c)  The patient has an elevated white blood cell (WBC) count of > 12,000/mm3

5. Other infectious etiologies and/or causes of the criteria listed in Inclusion Criteria #4 above have been excluded or are under control with broad spectrum antibiotic therapy.

6. At the time of screening, Candida sp. is growing in at least 1 non-sterile culture site (including, but not limited to urine, sputum, nares, pharynx, venous/arterial catheter tip, rectum, groin region, or fluid from drains in place for more  than 48 hours,).  NOTE:  Culture must have been obtained while the patient was in the ICU.  There is no quantitative cutoff requirement for positivity of the Candida sp. from this culture.

7. For women of childbearing potential, the patient has a negative serum or urine pregnancy test sensitive to 25 IU HCG prior to enrollment into the study. 

Exclusion Criteria

A subject will not be enrolled if they meet any of the following criteria:

  1. A female patient is pregnant or breast feeding.
  2. The patient has a history of allergy, hypersensitivity, or any serious reaction to caspofungin or another member of the echinocandin class (e.g., micafungin, anidulafungin).
  3. The patient has neutropenia, as defined as an absolute neutrophil count of <500/mm3 at study entry, or is expected to develop neutropenia during study therapy.
  4. The patient has a diagnosis of AIDS, aplastic anemia, or chronic granulomatous disease at study entry.
  5. The patient has a diagnosis of moderate or severe hepatic insufficiency, as defined by a Child Pugh score of 7 or greater (see Appendix 6.3).
  6. The patient is not expected to survive at least 24 hours.
  7. The patient has received systemic (IV or oral) antifungal therapy within 10 days prior to study entry.
  8. The patient has an active diagnosis of proven or probable invasive fungal infection, as per EORTC/MSG criteria (see Appendix 6.4 [15])
  9. The patient has previously participated in this study.
  10. The patient is currently on an investigational agent or has received an investigational agent within the 10 days prior to study entry.
  11. The patient has any condition or concomitant illness which, in the opinion of the investigator, might confuse the results of the study or pose additional risk in administering the study therapy to the patient.