Krause and colleagues conducted a multicenter, randomized, double-blind, double-dummy, non-inferiority study to compare the efficacy and safety of IV anidulafungin and oral fluconazole (Diflucan drug, Pfizer) for the treatment of esoph-ageal candidiasis. The study took place in the U.S., South Africa, Thailand, and Argentina. A total of 300 patients were randomly assigned to receive anidula-fungin 100 mg IV on day one, followed by 50 mg IV daily, and 301 patients received fluconazole 200 mg orally on day one, followed by 100 mg orally daily. The treatments were continued for seven days after resolution of symptoms but not for less than 14 days or more than 21 days.
To be enrolled in the study, patients had to have been given a diagnosis of esophageal candidiasis and had to have a predisposing factor for fungal infection, including antibiotics, corticosteroids, radiation therapy, myelosuppression, malnutrition, or acquired immunodeficiency syndrome (AIDS). Patients were excluded from enrollment:
- if they had a systemic fungal infection, ulcerative esophageal lesions, or hypersensitivity to the study drugs
- if they had taken a systemic antifungal agent in the week prior to enrollment
- if liver enzyme levels (alanine and aspartate transami-nases [ALT and AST]) were more than three times the upper limit of normal
- if they had fewer than 500 neutrophils per mm3
- if they had fewer than 60,000 platelets/mm3
The primary efficacy endpoint was an endoscopic response in the per-protocol set of patients at the end of therapy. For this endpoint, 97.2% of patients in the anidulafungin group and 98.8% in the fluconazole group showed treatment success, which included both cure and improvement (treatment difference -1.6%, 95% confidence interval [CI], -4.1 to 0.8), which indicated non-inferiority (Table 3).
Table 3 Esophageal Candidiasis Study Resuits (Per-Protocol Population)
|Endoscopic Response||Clinical Success||
|Anidulafungin* Fluconazole^||Anidulafungin Fluconazole||
|End of therapy 97.2% 98.8% Follow-up 64.4% 89.5%||98.8% 99.6%||
|* Eraxis, Pfizer. f Diflucan, Pfizer.Data from Krause DS,Simjee AE,von Rensburg C,et al.Clin Infect Dis 2004;39:770-775.10|
The intent-to-treat analysis showed similar results: 86.7% of patients receiving anidulafungin showed an endoscopic response, compared with 88% of those receiving fluconazole (95% CI, -0.67 to 3.9).
Clinical success was documented in 98.8% of the anidulafungin subjects and in 99.6% of the canadian fluconazole patients. Myco-logical success was seen in 86.7% of the anidulafungin patients and in 90.6% of the patients in the fluconazole group. At the two-week follow-up visit, 64.4% of the anidulafungin patients had sustained endoscopic success, in contrast to 89.5% of the fluconazole group (95°% CI, -32.5 to -17.8°%) (P < .001).
Treatment-related adverse drug events (ADEs) were seen in 9.3% of the anidulafungin patients and in 12% of the fluconazole patients. The most common ADEs were neutropenia, nausea, headache, and phlebitis or thrombophlebitis. The most common treatment-related laboratory abnormalities were elevated gamma-glutamyl transferase (GGT), ALT, and AST concentrations.
Invasive Candidiasis and Candidemia
A phase 2 randomized, dose-ranging study evaluated the safety and efficacy of anidulafungin in patients with invasive candidiasis and candidemia. A total of 120 patients were chosen to receive anidulafungin IV once daily at a dose of 50 mg (40 patients), 75 mg (40 patients), or 100 mg (40 patients). All patients started with a loading dose of twice the maintenance dose, given as a single infusion on the first day. Treatment was continued until two weeks after symptoms resolved.
Patients were eligible to be enrolled in the study if they were 18 years of age or older and had invasive candidiasis. Patients who had received an antifungal agent within seven days of enrollment, pregnant or lactating women, and patients with hypersensitivity to the study drug were ineligible.
The primary efficacy measure was a global response in the per-protocol population at the follow-up visit, which occurred two weeks after the end of therapy. Successful global response included both clinical and microbiological responses. canadian antibiotics
At the follow-up visit, global success was seen in the patient groups as follows: 72% of the patients receiving anidulafungin 50 mg, 85% of those receiving 75 mg, and 83% of those receiving 100 mg. Clinical and microbiological success rates were similar at 88% and 84% in the 50-mg group, 90% and 93% in the 75-mg group, and 89% and 89% in the 100-mg group, re-spectively.
The most common ADEs in this study were hypotension, nausea, vomiting, constipation, and pyrexia. No dose-response relationship was seen with respect to ADEs. Laboratory test anomalies were not observed.