Clinical trial NCT00520234: Randomized Study of Caspofungin Prophylaxis Followed by Pre-emptive Therapy for Invasive Candidiasis in the Intensive Care Unit (ICU)
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Invasive Candidiasis
Keywords: Candida
Prophylaxis
High risk adults
Intensive care unit (ICU)
Lead sponsor: Mycoses Study Group
Sponsor class: NETWORK
Collaborators: name: Merck Sharp & Dohme LLC
First posted: 2007-08-23
Enrollment: 222
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Proven and Probable Invasive Candidiasis Based on Modified Mycoses Study Group/European Organization for Research and Treatment of Cancer (MSG/EORTC) Criteria.
timeFrame: Within 7 days after end of therapy
Secondary outcomes:
measure: Incidence of Proven Invasive Candidiasis by MSG/ EORTC Criteria.
timeFrame: Within 7 days of end of therapy
measure: All Cause Mortality
timeFrame: Within 7 days of end of therapy
measure: Initiation of Other Antifungals
timeFrame: Within 7 days after end of therapy
measure: Time to Development of Proven or Probable Invasive Candidiasis
timeFrame: Within 7 days after end of therapy
measure: Incidence of Proven and Probable Invasive Fungal Infections Other Than Invasive Candidiasis.
timeFrame: Within 7 days after end of therapy
measure: Time to Beta Glucan Negativity in Pre-emptive Phase.
timeFrame: Within 14 days after end of therapy
measure: Incidence of Complete and Partial Response by Clinical and Microbiological or Serological Evidence for Subjects on the Pre-emptive Therapy Phase.
timeFrame: Within 14 days after end of therapy
measure: 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.
timeFrame: Hospital discharge
measure: Subjects Who Discontinue Study Therapy Due to a Drug-related Adverse Event
timeFrame: Up to 14 days after end of therapy
measure: Subjects With 1 or More Serious Drug-related Adverse Event(s)
timeFrame: Up to 14 days after end of therapy
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Los Angeles
country: United States
facility: University of Southern California
state: California
city: Denver
country: United States
facility: University of Colorado
state: Colorado
city: Washington
country: United States
facility: Washington Hospital Center
state: District of Columbia
city: New Orleans
country: United States
facility: Tulane University
state: Louisiana
city: Detroit
country: United States
facility: Harper University Hospital/ Wayne State
state: Michigan
city: Detroit
country: United States
facility: Henry Ford Hospital
state: Michigan
city: Missoula
country: United States
facility: St. Patrick's Hospital
state: Montana
city: Camden
country: United States
facility: Cooper University Hospital
state: New Jersey
city: Columbus
country: United States
facility: The Ohio State University
state: Ohio
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: Charleston
country: United States
facility: Medical Center of South Carolina
state: South Carolina
Study officials:
affiliation: The University of Texas Health Science Center, Houston
name: Luis Ostrosky-Zeichner, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Mycoses Study Group
name: Peter G Pappas, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.