LB 15 MSG-01: A Multicenter, Randomized, Double-Blind, Placebo Controlled Trial of Caspofungin (CAS) Prophylaxis vs Placebo Followed by Pre-Emptive Therapy for Invasive Candidiasis (IC) in High-Risk Adults in the Critical Care Setting. Preliminary Results

Sunday, April 3, 2011: 3:45 PM
Coronado BCD (Hilton Anatole)
Luis Ostrosky-Zeichner , University of Texas Medical School at Houston, Houston, TX
Shmuel Shoham , Mycoses Study Group, Birmingham, AL
Jose Vazquez , Mycoses Study Group, Birmingham, AL
Annette Reboli , Mycoses Study Group, Birmingham, AL
Robert Betts , Mycoses Study Group, Birmingham, AL
Michelle Barron , Mycoses Study Group, Birmingham, AL
Mindy Schuster , Mycoses Study Group, Birmingham, AL
Marc A. Judson , Mycoses Study Group, Birmingham, AL
Sanjay Revankar , Mycoses Study Group, Birmingham, AL
Juan Pablo Caeiro , Mycoses Study Group, Birmingham, AL
Julie E. Mangino , Mycoses Study Group, Birmingham, AL
David Mushatt , Mycoses Study Group, Birmingham, AL
Roger Bedimo , Mycoses Study Group, Birmingham, AL
Allison Freifeld , Mycoses Study Group, Birmingham, AL
M. Hong Nguyen , Mycoses Study Group, Birmingham, AL
Carol Kauffman , Mycoses Study Group, Birmingham, AL
Robert A. Larsen , Mycoses Study Group, Birmingham, AL
William E. Dismukes , Mycoses Study Group, Birmingham, AL
Andy O. Westfall , Mycoses Study Group, Birmingham, AL
Jeanna Beth Deerman , Mycoses Study Group, Birmingham, AL
Craig Wood , Merck & Co, Inc, North Wales, PA
Jack D. Sobel , Mycoses Study Group, Birmingham, AL
Peter G. Pappas , Mycoses Study Group, Birmingham, AL
Background: IC is the 3rd most common bloodstream infection in the ICU. It is associated with significant morbidity/mortality.

Objective: We investigated the use of CAS for prophylaxis and pre-emptive therapy of IC in the ICU.

Methods: We conducted a multicenter, randomized, double-blind, placebo controlled trial of CAS 50mg IV/day as prophylaxis vs placebo for the duration of ICU stay in 222 adults who were hospitalized for at least 3 days, were ventilated, received antibiotics, had a central venous catheter at any time in the first 3 days, and had at least one other risk factor for IC: parenteral nutrition or dialysis (any of days 1 through 3 of ICU), major surgery, pancreatitis, or systemic steroids, or other immunosuppressive agents within 7 days prior to or on ICU admission. Subjects were followed daily for IC. (1,3)-b-D-glucan (BG) levels were monitored 2x/week. The primary endpoint was incidence of proven or probable IC by EORTC/MSG criteria. The endpoint was assessed by the investigator and a data review committee (DRC). Patients were followed for 14 days after completion of therapy. Patients that had IC at baseline or who met the endpoint received pre-emptive therapy with open label CAS. The MITT/prophylaxis population (primary efficacy analysis population), as defined by the DRC, included patients that received at least 1 dose of CAS and did not have IC at baseline (186). The safety/pre-emptive population included patients (219) that received at least 1 dose of CAS.

Results: Demographics, frequency of primary endpoint, and frequency of AEs are shown in the table. There were no significant differences in the secondary endpoints of mortality, initiation of other antifungals, hospital LOS, or ICU LOS.

Conclusions: We identified a selected population at high risk for IC. CAS was safe and trended to reduce the incidence of IC when used for prophylaxis or as part of a pre-emptive therapy strategy.

 

 

PLACEBO

CAS

P value*

EFFICACY/PROPHYLAXIS ANALYSIS

 

 

 

Population n

84

102

 

Mean (+/-SD) age

55.4 (16.8)

57.7 (17.4)

 

Male sex (%)

59.5

62.7

 

Mean (+/-SD) APACHE II

24.9 (8.6)

25.0 (8.1)

 

Proven and probable IC (%) by Investigator

15.5

5.9

0.03

Proven and probable IC (%) by DRC

16.7

9.8

0.14

Proven IC (%) by DRC

4.8

1.0

0.1

 

 

 

 

SAFETY/PRE-EMPTIVE ANALYSIS

 

 

 

Population n

102

117

 

Mean (+/-SD) age

56.7 (16.6)

58.2 (17.6)

 

Male sex (%)

59.8

60.7

 

Mean (+/-SD) APACHE II

25.1 (8.7)

25.3 (8.0)

 

Proven and probable IC (%) by Investigator

25.5

13.7

0.02

Proven and probable IC (%) by DRC

30.4

18.8

0.04

Proven IC (%) by DRC

6.9

0.9

0.02

Patients with AE (%)

84.5

89.8

 

Patients with drug-related AE (%)

2.0

2.6

 

Patients with an SAE (%)

27.5

28.2

 

Patients with a drug-related SAE (%)

0

0.8

 

Patients with drug discontinuation due to drug-related AE (%)

2.0

1.7

 

* Cochran-Mantel-Haenszel test stratified by APACHE II score.