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An Open Label, Non-Comparative, Multicenter, Phase III Trial of the Efficacy, Safety and Toleration of Voriconazole in the Primary or Secondary Treatment of Invasive Fungal Infections

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT00001810
First Posted: December 10, 2002
Last Update Posted: March 4, 2008
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by:
National Institutes of Health Clinical Center (CC)
  Purpose
The objective of this study is to evaluate the efficacy, safety and toleration of voriconazole in the primary treatment of systemic or invasive fungal infections due to fungal pathogens for which there is no licensed therapy; and in the secondary treatment of systemic or invasive fungal infections in patients failing or intolerant to treatment with approved systemic antifungal agents. This trial is a Phase II multicenter, open label study investigating the utilization of voriconazole for the treatment of systemic or invasive fungal infections. Enrollment is targeted for 150 patients to be recruited from multiple centers. The patient population will consist of patients with proven, deeply invasive fungal infection for which there is no licensed therapy or if the patient is failing or intolerant to treatment with approved systemic antifungal agents. Voriconazole will be administered initially by a loading dose of 6 mg/kg q12 hours for the first two doses followed by 4 mg/kg q12 hours. Efficacy will be evaluated by clinical, radiological and microbiological response.

Condition Intervention Phase
Aspergillosis Candidiasis Fungemia Mycoses Drug: Voriconazole Phase 3

Study Type: Interventional
Study Design: Primary Purpose: Treatment
Official Title: An Open Label, Non-Comparative, Multicenter, Phase III Trial of the Efficacy, Safety and Toleration of Voriconazole in the Primary or Secondary Treatment of Invasive Fungal Infections

Resource links provided by NLM:


Further study details as provided by National Institutes of Health Clinical Center (CC):

Estimated Enrollment: 300
Study Start Date: April 1999
Estimated Study Completion Date: October 2000
Detailed Description:
The objective of this study is to evaluate the efficacy, safety and toleration of voriconazole in the primary treatment of systemic or invasive fungal infections due to fungal pathogens for which there is no licensed therapy; and in the secondary treatment of systemic or invasive fungal infections in patients failing or intolerant to treatment with approved systemic antifungal agents. This trial is a Phase III multicenter, open label study investigating the utilization of voriconazole for the treatment of systemic or invasive fungal infections. Enrollment is targeted for 150 patients to be recruited from multiple centers. The patient population will consist of patients with proven, deeply invasive fungal infection for which there is no licensed therapy or if the patient is failing or intolerant to treatment with approved systemic antifungal agents. Voriconazole will be administered initially by a loading dose of 6 mg/kg q12 hours for the first two doses followed by 4 mg/kg q12 hours. Efficacy will be evaluated by clinical, radiological and microbiological response.
  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   Child, Adult, Senior
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Males or (non-pregnant) females greater than or equal to 12 years of age.

Patients must have one of the following systemic or invasive fungal infections at baseline: systemic or invasive infection due to a fungal pathogen for which there is currently no licensed treatment or systemic or invasive fungal infection, with evidence of failure and/or intolerance/toxicity to treatment with approved systemic antifungal agents.

Definitions of failure to treatment with approved systemic antifungal agents:

For invasive aspergillosis and other invasive fungal infections - lack of clinical response after at least 7 days of systemic antifungal treatment at adequate doses;

For candida esophagitis only - lack of clinical response after at least 14 days of fluconazole at a dose of greater than or equal to 200 mg/day.

Definition of intolerance/toxicity to treatment with approved systemic antifungal agents:

Intolerance to the infusion-related toxicities of amphotericin B preparations despite appropriate supportive therapy, OR;

Nephrotoxicity defined as a serum creatinine that had increased by greater than 1.5 mg/dl while receiving amphotericin B therapy, OR;

Pre-existing renal impairment defined as a serum creatinine that increased to greater than 2.0 mg/dl due to reasons other than amphotericin B therapy.

The systemic or invasive fungal infection must be present at baseline and documented within four weeks preceding study entry as follows: positive histopathology with evidence of tissue invasion by fungal elements or positive serology where diagnostic (CSF cryptococcal antigen; serum or CSF Coccidioides antibody; serum, CSF or urine Histoplasma antigen) or positive mycologic culture from a normally sterile site, taken during the current episode of infection.

Women of child bearing potential (or less than 2 years post-menopausal) must have a negative serum pregnancy test at baseline, and must agree to use barrier methods of contraception during the study. Women may not be pregnant or lactating.

Signed written informed consent must be obtained at baseline.

Assent will be obtained from minors capable of understanding.

Subjects may not have previously participated in this trial.

Patients may not be receiving or be unable to discontinue the following drugs at least 24 hours prior to randomization: terfenadine, cisapride and astemizole (due to the possibility of QTc prolongation).

Patients may not be receiving or be unable to discontinue sulphonylureas at least 24 hours prior to randomization (as these compounds have a narrow therapeutic window and an increase in plasma levels may lead to hypoglycemia).

Patients may not have received the following drugs within 14 days prior to randomization: rifampin, carbamazepine and barbiturates as these are potent inducers of hepatic enzymes and will result in undetectable levels of voriconazole.

Patients may not be participating in a blinded trial of any investigational drug.

Patients may not have AST, ALT, total bilirubin or alkaline phosphatase greater than 5 times the upper limit normal.

No patients with a serum creatinine greater than 3.5 mg/dl or with end-stage renal disease requiring chronic dialysis.

Patients may not have allergic bronchopulmonary aspergillosis, aspergilloma, zygomycoses, isolated candiduria, and/or catheter-or-device-related candidemia.

Patients may not have fungal infections not considered to be invasive or systemic including dermatophytosis and oropharyngeal candidiasis.

Patients may not be receiving or likely to receive any investigational drug (any unlicensed new chemical entity), except one of the following classes of medications: cancer chemotherapeutic agents, antiretrovirals, or other therapies for HIV/AIDS-related opportunistic infections.

Patients may not be receiving or likely to receive the following medications or treatments during the study period:

G-CSF or GM-CSF (for other than treatment of granulocytopenia);

Any systemic antifungal medication;

White blood cell transfusions.

Patients may not have hypersensitivity or intolerance to azole antifungal agents including miconazole, ketocanazole, fluconazole, or itraconazole.

Patients must have a life expectancy greater than 72 hours.

Patients may not have any condition which, in the opinion of the investigator, could affect subject safety, preclude evaluation of response, or render it unlikely that the contemplated course of therapy can be completed.

  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00001810


Locations
United States, Maryland
National Cancer Institute (NCI)
Bethesda, Maryland, United States, 20892
Sponsors and Collaborators
National Cancer Institute (NCI)
  More Information

ClinicalTrials.gov Identifier: NCT00001810     History of Changes
Other Study ID Numbers: 990094
99-C-0094
First Submitted: November 3, 1999
First Posted: December 10, 2002
Last Update Posted: March 4, 2008
Last Verified: April 2000

Keywords provided by National Institutes of Health Clinical Center (CC):
Antifungal Agent
Aspergillosis
Candidiasis
Fungemia

Additional relevant MeSH terms:
Mycoses
Candidiasis
Aspergillosis
Invasive Fungal Infections
Fungemia
Hyalohyphomycosis
Dermatomycoses
Lung Diseases, Fungal
Skin Diseases, Infectious
Skin Diseases
Sepsis
Infection
Systemic Inflammatory Response Syndrome
Inflammation
Pathologic Processes
Voriconazole
Antifungal Agents
Anti-Infective Agents
14-alpha Demethylase Inhibitors
Cytochrome P-450 Enzyme Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Steroid Synthesis Inhibitors
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Cytochrome P-450 CYP3A Inhibitors