Posaconazole to Treat Invasive Fungal Infections

Sponsor

National Institute of Allergy and Infectious Diseases (NIAID) (NIH)

Overall Status

Completed

CT.gov ID

NCT00033982

Collaborator

(none)

Enrollment

Location

58.3

Duration (Months)

0.9

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This study will evaluate the safety and effectiveness of posaconazole for treating invasive fungal infections. New therapies for these infections are needed for patients who do not respond, to or cannot tolerate, standard treatment. These patients include those with immune defects who have significant side effects from treatment with amphotericin or other antifungals.

Patients 13 years of age or older who are on other primary NIH protocols with an invasive fungal infection 1) that does not respond to standard antifungal therapies; 2) for which there is no effective therapy; 3) who develop serious side effects from their current treatment; or 4) who have organ dysfunction that does not permit use of standard antifungal treatments may be eligible for this study. Candidates will be screened with a medical history, including a review of current and previous antifungal treatments, pregnancy test for women of childbearing potential, electrocardiogram (EKG), and detailed neurologic examination.

Participants will take either 200 mg (1 teaspoonful) of liquid posaconazole by mouth four times a day or 400 mg (two teaspoonfuls) twice a day for a period of 28 days to 24 months. (The physician will determine the duration of treatment.) Patients will have monthly follow-up visits during the treatment period and 1 month after treatment is completed for the following procedures:

Detailed neurologic exam every 3 months
Blood tests every month
EKG every month
Imaging studies, including chest x-ray, computed tomography (CT), magnetic resonance imaging (MRI) radionuclide scanning or ultrasound, every month until the infection has been stable for three determinations. Thereafter, imaging studies will be done every 3 months as long as the infection remains stable or improves.

On the last day of the study treatment period, participants will have a detailed neurologic exam and review of medications and medical complaints since their last visit.

Condition or Disease	Intervention/Treatment	Phase
Granulomatous Disease, Chronic Job's Syndrome Infection	Drug: Posaconazole	Phase 3

Detailed Description

We seek to use the experimental triazole antifungal, Posaconazole, in the treatment of patients with invasive fungal infections that are resistant or refractory to the best available treatment, or who are unable to tolerate the best available treatment. We have observed significant short and long term toxicities from amphotericin and its various preparations in our patients with chronic granulomatous disease (CGD) and Hyper IgE recurrent infection syndrome (HIE or Job's). We now have now had 5 CGD patients on dialysis, and several more have progressive renal failure, all thought due to high dose, prolonged amphotericin. In addition, many of our more severely affected CGD patients have had multiple thoracic surgeries, leading to reduced lung capacity. Several of our HIE patients have persistent fungal lung infections that have not cleared with extensive therapy with amphotericin and/or other new triazole antifungals. Therefore, agents of high tolerability and high potency are still desperately needed. Posaconazole has a broad spectrum of action against a large number of molds and fungi at easily achievable concentrations in plasma. It has a favorable toxicity profile and has performed well in clinical trials to date. This drug will be administered orally twice daily. Close monitoring of tolerance, toxicity, and efficacy will be performed. We anticipate enrollment of up to 50 patients over the next 2 years.

Study Design

Study Type:

Interventional

Primary Purpose:

Treatment

Official Title:

Open Label, Limited Access Protocol of Posaconazole in Invasive Fungal Infections

Study Start Date :

Apr 11, 2002

Study Completion Date :

Feb 20, 2007

Outcome Measures

Primary Outcome Measures

Eligibility Criteria

Criteria

Ages Eligible for Study:

2 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

INCLUSION CRITERIA:

As set out in the company protocol.

All subjects must have a proven or probable fungal infection that is resistant to standard therapy, or to which therapy the patient is significantly intolerant. (Intolerance must include signs of intolerance such as fever, rigors, laboratory, abnormalities, as well as subjective symptoms).

Only subjects age 2 years and older will be eligible at this time.