Posaconazole or fluconazole for prophylaxis in severe graft-versus-host disease.
BACKGROUND
Invasive fungal infections are an important cause of morbidity and mortality after allogeneic hematopoietic stem-cell transplantation.


METHODS
In an international, randomized, double-blind trial, we compared oral posaconazole with oral fluconazole for prophylaxis against invasive fungal infections in patients with graft-versus-host disease (GVHD) who were receiving immunosuppressive therapy. The primary end point was the incidence of proven or probable invasive fungal infections from randomization to day 112 of the fixed treatment period of the study.


RESULTS
Of a total of 600 patients, 301 were assigned to posaconazole and 299 to fluconazole. At the end of the fixed 112-day treatment period, posaconazole was found to be as effective as fluconazole in preventing all invasive fungal infections (incidence, 5.3% and 9.0%, respectively; odds ratio, 0.56; 95 percent confidence interval [CI], 0.30 to 1.07; P=0.07) and was superior to fluconazole in preventing proven or probable invasive aspergillosis (2.3% vs. 7.0%; odds ratio, 0.31; 95% CI, 0.13 to 0.75; P=0.006). While patients were receiving study medications (exposure period), in the posaconazole group, as compared with the fluconazole group, there were fewer breakthrough invasive fungal infections (2.4% vs. 7.6%, P=0.004), particularly invasive aspergillosis (1.0% vs. 5.9%, P=0.001). Overall mortality was similar in the two groups, but the number of deaths from invasive fungal infections was lower in the posaconazole group (1%, vs. 4% in the fluconazole group; P=0.046). The incidence of treatment-related adverse events was similar in the two groups (36% in the posaconazole group and 38% in the fluconazole group), and the rates of treatment-related serious adverse events were 13% and 10%, respectively.


CONCLUSIONS
Posaconazole was similar to fluconazole for prophylaxis against fungal infections among patients with GVHD. It was superior in preventing invasive aspergillosis and reducing the rate of deaths related to fungal infections. (ClinicalTrials.gov number, NCT00034645 [ClinicalTrials.gov].).
Ullmann
Andrew J
AJ
Johannes Gutenberg University, Mainz, Germany. ullmann@uni-mainz.de
Lipton
Jeffrey H
JH
Vesole
David H
DH
Chandrasekar
Pranatharthi
P
Langston
Amelia
A
Tarantolo
Stefano R
SR
Greinix
Hildegard
H
Morais de Azevedo
Wellington
W
Reddy
Vijay
V
Boparai
Navdeep
N
Pedicone
Lisa
L
Patino
Hernando
H
Durrant
Simon
S
D000293:Adolescent; D000328:Adult; D000368:Aged; D000935:Antifungal Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001228:Aspergillosis / Q000517:prevention & control; D004311:Double-Blind Method; D005260:Female; D015725:Fluconazole / Q000009:adverse effects / Q000627:therapeutic use*; D006086:Graft vs Host Disease / Q000150:complications / Q000188:drug therapy*; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009181:Mycoses / Q000401:mortality / Q000517:prevention & control*; D009894:Opportunistic Infections / Q000517:prevention & control*; D012307:Risk Factors; D014230:Triazoles / Q000009:adverse effects / Q000627:therapeutic use*
D000935:Antifungal Agents; D014230:Triazoles; C101425:posaconazole; D015725:Fluconazole