Randomized Study of Caspofungin Prophylaxis Followed by Pre-emptive Therapy for Invasive Candidiasis in the Intensive Care Unit (ICU) (MSG-01)

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

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.

Study Overview

• Status: Completed
• Conditions: Invasive Candidiasis
• Intervention / Treatment: Drug: Caspofungin; Drug: Normal Saline

• Study Type: Interventional
• Enrollment (Actual): 222
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35124
      • University of Alabama at Birmingham
  • California
    • Los Angeles, California, United States, 29425
      • University of Southern California
  • Colorado
    • Denver, Colorado, United States, 80262
      • University of Colorado
  • District of Columbia
    • Washington, District of Columbia, United States, 20010
      • Washington Hospital Center
  • Louisiana
    • New Orleans, Louisiana, United States, 70112
      • Tulane University
  • Michigan
    • Detroit, Michigan, United States, 48202
      • Henry Ford Hospital
    • Detroit, Michigan, United States, 48201
      • Harper University Hospital/ Wayne State
  • Montana
    • Missoula, Montana, United States, 59802
      • St. Patrick's Hospital
  • New Jersey
    • Camden, New Jersey, United States, 08103
      • Cooper University Hospital
  • Ohio
    • Columbus, Ohio, United States, 43210
      • The Ohio State University
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Medical Center of South Carolina

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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	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

Collaborators and Investigators

• Sponsor: Mycoses Study Group
• Collaborators: Merck Sharp & Dohme LLC
• Investigators: Principal Investigator: Luis Ostrosky-Zeichner, MD, The University of Texas Health Science Center, Houston; Principal Investigator: Peter G Pappas, MD, Mycoses Study Group

Publications and helpful links

General Publications

• Jarvis WR. Epidemiology of nosocomial fungal infections, with emphasis on Candida species. Clin Infect Dis. 1995 Jun;20(6):1526-30. doi: 10.1093/clinids/20.6.1526.
• Goodman JL, Winston DJ, Greenfield RA, Chandrasekar PH, Fox B, Kaizer H, Shadduck RK, Shea TC, Stiff P, Friedman DJ, et al. A controlled trial of fluconazole to prevent fungal infections in patients undergoing bone marrow transplantation. N Engl J Med. 1992 Mar 26;326(13):845-51. doi: 10.1056/NEJM199203263261301.
• Diekema DJ, Messer SA, Brueggemann AB, Coffman SL, Doern GV, Herwaldt LA, Pfaller MA. Epidemiology of candidemia: 3-year results from the emerging infections and the epidemiology of Iowa organisms study. J Clin Microbiol. 2002 Apr;40(4):1298-302. doi: 10.1128/JCM.40.4.1298-1302.2002.
• Denning DW. Echinocandins: a new class of antifungal. J Antimicrob Chemother. 2002 Jun;49(6):889-91. doi: 10.1093/jac/dkf045. No abstract available.
• Ostrosky-Zeichner L, Shoham S, Vazquez J, Reboli A, Betts R, Barron MA, Schuster M, Judson MA, Revankar SG, Caeiro JP, Mangino JE, Mushatt D, Bedimo R, Freifeld A, Nguyen MH, Kauffman CA, Dismukes WE, Westfall AO, Deerman JB, Wood C, Sobel JD, Pappas PG. MSG-01: A randomized, double-blind, placebo-controlled trial of caspofungin prophylaxis followed by preemptive therapy for invasive candidiasis in high-risk adults in the critical care setting. Clin Infect Dis. 2014 May;58(9):1219-26. doi: 10.1093/cid/ciu074. Epub 2014 Feb 18.

Study record dates

Study Major Dates

• Study Start: August 1, 2007
• Primary Completion (Actual): March 1, 2010
• Study Completion (Actual): March 1, 2010

Study Registration Dates

• First Submitted: August 21, 2007
• First Submitted That Met QC Criteria: August 22, 2007
• First Posted (Estimate): August 23, 2007

Study Record Updates

• Last Update Posted (Estimate): May 9, 2011
• Last Update Submitted That Met QC Criteria: April 8, 2011
• Last Verified: April 1, 2011

More Information

Terms related to this study

• Keywords: Prophylaxis; Candida; Intensive care unit (ICU); High risk adults
• 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; Antifungal Agents; Caspofungin
• Other Study ID Numbers: MSG-01