A Study of Itraconazole in the Treatment and Prevention of Histoplasmosis, a Fungal Infection, in Patients With AIDS
Information source: National Institute of Allergy and Infectious Diseases (NIAID)
Information obtained from ClinicalTrials.gov on June 20, 2008
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: HIV Infections; Histoplasmosis
Intervention: Itraconazole (Drug)
Phase: Phase 2
Status: Completed
Sponsored by: National Institute of Allergy and Infectious Diseases (NIAID) Official(s) and/or principal investigator(s):
LJ Wheat, Study Chair
Summary
To evaluate the feasibility of itraconazole as (1) primary therapy in histoplasmosis and (2)
maintenance therapy after completion of primary therapy. To evaluate the effect of therapy of
CNS histoplasmosis. To determine if resistance to drug occurs in patients who fail therapy.
Histoplasmosis is a serious opportunistic infection in patients with AIDS. Although the
clinical response to amphotericin B treatment in the AIDS patients is generally good,
administration difficulties and toxicity detract from its usefulness. Oral treatment with
ketoconazole overcomes these limitations of amphotericin B, but does not appear to be
effective for primary treatment in patients with AIDS. Itraconazole is a triazole compound in
which preclinical studies have demonstrated activity against Histoplasmosis capsulatum.
Preclinical studies have also shown that itraconazole appears effective in the treatment of
histoplasmosis. The frequency of adverse reactions to itraconazole has been low in several
studies. Central nervous system (CNS) involvement occurs in up to 20 percent of patients with
histoplasmosis, and appears to have a poor response to amphotericin B treatment. Itraconazole
has been used successfully in a small number of patients with cryptococcal meningitis,
supporting a study of its use in CNS histoplasmosis.
Clinical Details
Official title: Pilot Study To Determine the Feasibility of Itraconazole for Primary Treatment and Suppression of Relapse of Disseminated Histoplasmosis in Patients With the Acquired Immunodeficiency Syndrome
Study design: Treatment
Detailed description:
Histoplasmosis is a serious opportunistic infection in patients with AIDS. Although the
clinical response to amphotericin B treatment in the AIDS patients is generally good,
administration difficulties and toxicity detract from its usefulness. Oral treatment with
ketoconazole overcomes these limitations of amphotericin B, but does not appear to be
effective for primary treatment in patients with AIDS. Itraconazole is a triazole compound
in which preclinical studies have demonstrated activity against Histoplasmosis capsulatum.
Preclinical studies have also shown that itraconazole appears effective in the treatment of
histoplasmosis. The frequency of adverse reactions to itraconazole has been low in several
studies. Central nervous system (CNS) involvement occurs in up to 20 percent of patients with
histoplasmosis, and appears to have a poor response to amphotericin B treatment. Itraconazole
has been used successfully in a small number of patients with cryptococcal meningitis,
supporting a study of its use in CNS histoplasmosis.
At least 30 patients with AIDS and an initial episode of disseminated histoplasmosis are
selected for this study. Up to 5 patients will have a diagnosis of CNS histoplasmosis.
Therapy with all other systemic antifungal agents must be halted before study entry. Patients
receive itraconazole for 3 days followed by daily oral doses for a total of 12 weeks.
Patients who are doing well clinically, without evidence of clinical failure or dose-limiting
toxicity, are permitted to continue maintenance therapy to prevent relapse at a reduced dose
for an additional 12 months. Patients who are being treated for CNS histoplasmosis will
continue to receive itraconazole.
Eligibility
Minimum age: 13 Years.
Maximum age: N/A.
Gender(s): Both.
Criteria:
Inclusion Criteria
Concurrent Medication:
Allowed:
- Vincristine, vinblastine, bleomycin, or interferon for Kaposi's sarcoma.
- Erythropoietin.
- Didanosine by exemption for 10 patients.
- Barbiturates.
- Coumarin-type anticoagulants.
- Oral contraceptives.
- Digoxin.
- Methadone.
- Narcotics.
- Acyclovir.
- Acetaminophen.
- Sulfonamides.
- Trimethoprim / sulfamethoxazole.
- Pentamidine for Pneumocystis carinii pneumonia (PCP) or PCP prophylaxis.
- Topical antifungals.
- Pyrimethamine.
- Ganciclovir.
- AZT.
- Stress doses of steroids in patients with adrenal insufficiency.
Concurrent Treatment:
Allowed:
- Dose reduction or interruption of myelosuppressive therapy and transfusion to maintain
hemoglobin of 7 or more g/dl.
- Radiation therapy.
Patient must:
- Show laboratory evidence of HIV infection and disseminated histoplasmosis.
- Be oriented to person, place, and time.
- Be able to give written informed consent (appropriate consent must be obtained from a
parent or legal guardian for patients under 18 years of age).
Allowed:
- Abnormal liver function tests in Grade 3 toxicity range if liver biopsy shows evidence
that histoplasmosis caused these abnormalities.
- Mucocutaneous candidiasis.
Prior Medication:
Allowed:
- Amphotericin B or ketoconazole for pulmonary histoplasmosis at least 3 months prior to
study entry.
- Azidothymidine (AZT).
- Vincristine, vinblastine, bleomycin, or interferon for mucocutaneous Kaposi's
sarcoma.
- Prophylaxis for Pneumocystis carinii pneumonia (PCP).
Exclusion Criteria
Co-existing Condition:
Patients with the following conditions or symptoms are excluded:
- Severely ill, or at risk of dying from histoplasmosis within the first week of
treatment, as indicated by systolic blood pressure less than 90 mm Hg , or PO2 less
than 60.
- Active CNS lesions, malignancies, or infections other than MAI.
- Severe malabsorption syndrome (persistent diarrhea more than 4 weeks duration with at
least 4 loose stools per day accompanied by a 10 percent or greater weight loss).
- Requiring cytotoxic therapy for malignancies.
- Any systemic fungal infection other than histoplasmosis.
- Systemic Mycobacterium avium intracellulare.
- Receiving treatment for other acute opportunistic infections whose signs and symptoms
have not yet resolved or stabilized.
- History of allergy to or intolerance of imidazoles or azoles.
Concurrent Medication:
Excluded:
- All other systemic antifungal agents.
- Investigational drugs not specifically allowed.
- Oral hypoglycemics.
- Rifamycins.
- Phenytoin.
- Carbamazepine.
- Steroids in excess of physiologic replacement doses not specifically allowed.
- Cytotoxic chemotherapy.
- Discouraged:
- Antacids.
- Sucralfate.
- H2 blockers.
Patients with the following are excluded:
- Severely ill, or at risk of dying from histoplasmosis within the first week of
treatment.
- Active CNS infections, malignancies or lesions not documented to be caused by
histoplasmosis, which would interfere with assessment of response.
- Unable to take oral medications reliably.
- Severe malabsorption syndrome.
- Requiring cytotoxic therapy for malignancies.
- Any systemic fungal infection other than histoplasmosis.
- Systemic Mycobacterium avium intracellulare.
- Receiving treatment for other acute opportunistic infections whose signs and symptoms
have not yet resolved or stabilized.
Prior Medication:
Excluded for greater than 1 week within the last 3 months:
- Fluconazole.
- Itraconazole.
- SCH 39304.
- Amphotericin B greater than 1. 5 mg/kg, or any other antifungal for this episode of
disseminated histoplasmosis.
Patients who the investigator feels would be undependable with regard to adherence to the
protocol.
Locations and Contacts
Los Angeles County - USC Med Ctr, Los Angeles, California 90033, United States
USC School of Medicine / Norris Cancer Hosp, Los Angeles, California 90033, United States
Northwestern Univ Med School, Chicago, Illinois 60611, United States
Indiana Univ Hosp, Indianapolis, Indiana 462025250, United States
Tulane Univ School of Medicine, New Orleans, Louisiana 70112, United States
Univ of Massachusetts Med Ctr, Worcester, Massachusetts 01655, United States
Univ of Minnesota, Minneapolis, Minnesota 55455, United States
Univ of Rochester Medical Center, Rochester, New York 14642, United States
Jack Weiler Hosp / Bronx Municipal Hosp, Bronx, New York 10465, United States
Cornell Univ Med Ctr, New York, New York 10021, United States
Saint Luke's - Roosevelt Hosp Ctr, New York, New York 10025, United States
Bronx Municipal Hosp Ctr/Jacobi Med Ctr, Bronx, New York 10461, United States
Montefiore Med Ctr / Bronx Municipal Hosp, Bronx, New York 10467, United States
Bronx Veterans Administration / Mount Sinai Hosp, Bronx, New York 10468, United States
Duke Univ Med Ctr, Durham, North Carolina 27710, United States
Holmes Hosp / Univ of Cincinnati Med Ctr, Cincinnati, Ohio 452670405, United States
Julio Arroyo, West Columbia, South Carolina 29169, United States
Additional Information
Click here for more information about Itraconazole
Related publications: Hecht FM, Wheat J, Korzun AH, Hafner R, Skahan KJ, Larsen R, Limjoco MT, Simpson M, Schneider D, Keefer MC, Clark R, Lai KK, Jacobson JM, Squires K, Bartlett JA, Powderly W. Itraconazole maintenance treatment for histoplasmosis in AIDS: a prospective, multicenter trial. J Acquir Immune Defic Syndr Hum Retrovirol. 1997 Oct 1;16(2):100-7. Wheat J, Hafner R, Korzun AH, Limjoco MT, Spencer P, Larsen RA, Hecht FM, Powderly W. Itraconazole treatment of disseminated histoplasmosis in patients with the acquired immunodeficiency syndrome. AIDS Clinical Trial Group. Am J Med. 1995 Apr;98(4):336-42.
Last updated: June 23, 2005
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