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Multi-center Comparison of Fluconazole (UK-49,858) and Amphotericin B as Treatment for Acute Cryptococcal Meningitis

18 Years
Not Enrolling
Meningitis, Cryptococcal, HIV Infections

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Trial Information

Multi-center Comparison of Fluconazole (UK-49,858) and Amphotericin B as Treatment for Acute Cryptococcal Meningitis

Cryptococcal meningitis is an important cause of disease and death among patients with AIDS.
Usually AMB is given either alone or with FLC to patients with this infection, but these
treatments are not always effective and both have toxic effects. Animal studies and
preliminary studies in humans show that FCZ is active in cryptococcal meningitis and suggest
that it may be less toxic than either AMB or FLC.

Patients accepted into the study are randomly assigned to FCZ or AMB. Patients assigned to
FCZ take FCZ by mouth daily for 10 weeks. Patients assigned to AMB are given intravenous
injections of AMB daily for 6-10 weeks. Non-AIDS patients assigned to AMB also take FLC by
mouth daily. The use of FLC in patients with AIDS is decided on an individual basis.
Patients with AIDS who respond satisfactorily to FCZ receive maintenance therapy to prevent
relapse for an additional 12 months. Patients with AIDS who respond to AMB may qualify for
another Pfizer Central Research protocol. Patients without AIDS who respond to therapy are
observed for 6 months for relapse. During therapy, samples of blood and cerebrospinal fluid
(by lumbar puncture) are taken periodically in order to evaluate the effectiveness of the
drug treatments and to identify possible toxic effects.

Inclusion Criteria

Inclusion Criteria

Concurrent Medication:


- Immunosuppressant therapy.

- Cyclosporin plasma concentrations should be monitored and appropriate dosage
adjustments made when used with amphotericin B or fluconazole.

- Antiviral therapy.

- Prophylaxis for Pneumocystis carinii pneumonia.

- Treatment of intercurrent opportunistic infection as long as no investigational
agent, or approved agent for an investigational indication, is used.

- Antipyretics, hydrocortisone, or meperidine to prevent or ameliorate side effects
associated with amphotericin B.

Concurrent Treatment:


- Radiation therapy for mucocutaneous Kaposi's sarcoma.

Patients must have:

- Written informed consent obtained from the patient or from the patient's legal

- One of the following:

- (1) Tentative identification of Cryptococcus neoformans in culture of lumbar
cerebrospinal fluid (CSF). Results of baseline cultures need not be available when
therapy is begun, but therapy is discontinued if the baseline CSF culture is later
found to be negative for C. neoformans, or (2) Clinical and CSF findings (cell count,
protein, glucose) compatible with cryptococcal meningitis plus one of the following:

- (a) Positive CSF India ink examination, (b) Culture or biopsy evidence of extraneural
cryptococcal infection, (c) Positive serum of CSF cryptococcal antigen test, or
increase in titer for previously treated patients with suspected relapse, or (d)
Biopsy evidence of central nervous system cryptococcal infection.

- Treatment status of either no prior systemic antifungal therapy for cryptococcosis or
relapse after prior therapy. The success of prior therapy must have been documented
by negative CSF culture at the end of therapy.

Prior Medication:

Allowed within 4 weeks of study entry:

- Successful prior therapy for cryptococcosis, but no more than 1 mg/kg/week amphotericin


- Immunosuppressant therapy.

- Antiviral therapy.

- Prophylaxis for Pneumocystis carinii pneumonia.

Exclusion Criteria

Co-existing Condition:


- Acute or chronic meningitis based on any etiology other than cryptococcosis.

- History of allergy to or intolerance of imidazoles, or amphotericin B.

- Moderate or severe liver disease defined as any one or more of the following:

- SGOT or SGPT > 5 x upper limit of normal, total bilirubin > 2.5 mg/dl, prothrombin
time > 5 seconds over control, or alkaline phosphatase > 2 x upper limit of normal.

- Comatose patients.

Concurrent Medication:


- Drugs with low therapeutic ratios that undergo hepatic metabolism may not be used
with fluconazole until possible drug interactions have been clarified.

- Coumarin-type anticoagulants.

- Oral hypoglycemics.

- Barbiturates.

- Immunostimulants.

- Investigational drugs or approved (licensed) drugs for investigational indications.

- Systemic antifungal agent other than the assigned study drug.

Concurrent Treatment:


Lymphocyte replacement.

Prior Medication:

Excluded within 4 weeks of study entry:

- More than 1 mg/kg/week amphotericin B.

Patients unlikely to survive more than 2 weeks.

Type of Study:


Study Design:

Intervention Model: Parallel Assignment, Primary Purpose: Treatment

Principal Investigator

Armstrong D

Investigator Role:

Study Chair


United States: Federal Government

Study ID:

ACTG 059



Start Date:

Completion Date:

Related Keywords:

  • Meningitis, Cryptococcal
  • HIV Infections
  • AIDS-Related Opportunistic Infections
  • Meningitis
  • Injections, Intravenous
  • Cryptococcus neoformans
  • Cryptococcosis
  • Drug Therapy, Combination
  • Fluconazole
  • Administration, Oral
  • Acquired Immunodeficiency Syndrome
  • Amphotericin B
  • HIV Infections
  • Acquired Immunodeficiency Syndrome
  • Meningitis
  • Meningitis, Cryptococcal



Mem Sloan - Kettering Cancer Ctr New York, New York  10021
Julio Arroyo West Columbia, South Carolina  29169
Univ of Miami School of Medicine Miami, Florida  331361013
Tulane Univ School of Medicine New Orleans, Louisiana  70112
Bronx Municipal Hosp Ctr/Jacobi Med Ctr Bronx, New York  10461
Univ of North Carolina Chapel Hill, North Carolina  275997215