Clinical Trials Logo

Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT00000708
Other study ID # ACTG 059
Secondary ID Protocol 159Proj
Status Completed
Phase N/A
First received November 2, 1999
Last updated March 11, 2011

Study information

Verified date July 1991
Source National Institute of Allergy and Infectious Diseases (NIAID)
Contact n/a
Is FDA regulated No
Health authority United States: Federal Government
Study type Interventional

Clinical Trial Summary

To compare the safety and effectiveness of fluconazole (FCZ) and amphotericin B (AMB), alone or in combination with flucytosine (FLC), as treatment for acute cryptococcal meningitis in patients who have not been treated previously or who have relapsed after a previous successful treatment.

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.


Description:

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.


Recruitment information / eligibility

Status Completed
Enrollment 120
Est. completion date
Est. primary completion date July 1991
Accepts healthy volunteers No
Gender Both
Age group 18 Years and older
Eligibility Inclusion Criteria

Concurrent Medication:

Allowed:

- 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:

Allowed:

- Radiation therapy for mucocutaneous Kaposi's sarcoma.

Patients must have:

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

- 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 B.

Allowed:

- Immunosuppressant therapy.

- Antiviral therapy.

- Prophylaxis for Pneumocystis carinii pneumonia.

Exclusion Criteria

Co-existing Condition:

Excluded:

- 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:

Excluded:

- 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:

Excluded:

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.

Study Design

Intervention Model: Parallel Assignment, Primary Purpose: Treatment


Related Conditions & MeSH terms


Intervention

Drug:
Flucytosine

Fluconazole

Amphotericin B


Locations

Country Name City State
United States Bronx Municipal Hosp Ctr/Jacobi Med Ctr Bronx New York
United States Univ of North Carolina Chapel Hill North Carolina
United States Univ of Miami School of Medicine Miami Florida
United States Tulane Univ School of Medicine New Orleans Louisiana
United States Mem Sloan - Kettering Cancer Ctr New York New York
United States Julio Arroyo West Columbia South Carolina

Sponsors (1)

Lead Sponsor Collaborator
National Institute of Allergy and Infectious Diseases (NIAID)

Country where clinical trial is conducted

United States, 

References & Publications (3)

Powderly WG, Cloud GA, Dismukes WE, Saag MS. Measurement of cryptococcal antigen in serum and cerebrospinal fluid: value in the management of AIDS-associated cryptococcal meningitis. Clin Infect Dis. 1994 May;18(5):789-92. — View Citation

Powderly WG. Recent advances in the management of cryptococcal meningitis in patients with AIDS. Clin Infect Dis. 1996 May;22 Suppl 2:S119-23. Review. — View Citation

Saag MS, Powderly WG, Cloud GA, Robinson P, Grieco MH, Sharkey PK, Thompson SE, Sugar AM, Tuazon CU, Fisher JF, et al. Comparison of amphotericin B with fluconazole in the treatment of acute AIDS-associated cryptococcal meningitis. The NIAID Mycoses Study Group and the AIDS Clinical Trials Group. N Engl J Med. 1992 Jan 9;326(2):83-9. — View Citation

See also
  Status Clinical Trial Phase
Completed NCT05454514 - Automated Medication Platform With Video Observation and Facial Recognition to Improve Adherence to Antiretroviral Therapy in Patients With HIV/AIDS N/A
Completed NCT03760458 - The Pharmacokinetics, Safety, and Tolerability of Abacavir/Dolutegravir/Lamivudine Dispersible and Immediate Release Tablets in HIV-1-Infected Children Less Than 12 Years of Age Phase 1/Phase 2
Completed NCT03141918 - Effect of Supplementation of Bioactive Compounds on the Energy Metabolism of People Living With HIV / AIDS N/A
Completed NCT03067285 - A Phase IV, Open-label, Randomised, Pilot Clinical Trial Designed to Evaluate the Potential Neurotoxicity of Dolutegravir/Lamivudine/Abacavir in Neurosymptomatic HIV Patients and Its Reversibility After Switching to Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide. DREAM Study Phase 4
Recruiting NCT04579146 - Coronary Artery Disease (CAD) in Patients HIV-infected
Completed NCT06212531 - Papuan Indigenous Model of Male Circumcision N/A
Active, not recruiting NCT03256422 - Antiretroviral Treatment Taken 4 Days Per Week Versus Continuous Therapy 7/7 Days Per Week in HIV-1 Infected Patients Phase 3
Completed NCT03256435 - Retention in PrEP Care for African American MSM in Mississippi N/A
Completed NCT00517803 - Micronutrient Supplemented Probiotic Yogurt for HIV/AIDS and Other Immunodeficiencies N/A
Active, not recruiting NCT03572335 - Systems Biology of Diffusion Impairment in Human Immunodeficiency Virus (HIV)
Completed NCT04165200 - Fecal Microbiota Transplantation as a Therapeutic Strategy for Patients Infected With HIV N/A
Recruiting NCT03854630 - Hepatitis B Virus Vaccination in HIV-positive Patients and Individuals at High Risk for HIV Infection Phase 4
Terminated NCT03275571 - HIV, Computerized Depression Therapy & Cognition N/A
Completed NCT02234882 - Study on Pharmacokinetics Phase 1
Completed NCT01618305 - Evaluating the Response to Two Antiretroviral Medication Regimens in HIV-Infected Pregnant Women, Who Begin Antiretroviral Therapy Between 20 and 36 Weeks of Pregnancy, for the Prevention of Mother-to-Child Transmission Phase 4
Recruiting NCT05043129 - Safety and Immune Response of COVID-19 Vaccination in Patients With HIV Infection
Not yet recruiting NCT05536466 - The Influence of Having Bariatric Surgery on the Pharmacokinetics, Safety and Efficacy of the Novel Non-nucleoside Reverse Transcriptase Inhibitor Doravirine N/A
Recruiting NCT04985760 - Evaluation of Trimer 4571 Therapeutic Vaccination in Adults Living With HIV on Suppressive Antiretroviral Therapy Phase 1
Completed NCT05916989 - Stimulant Use and Methylation in HIV
Terminated NCT02116660 - Evaluation of Renal Function, Efficacy, and Safety When Switching From Tenofovir/Emtricitabine Plus a Protease Inhibitor/Ritonavir, to a Combination of Raltegravir (MK-0518) Plus Nevirapine Plus Lamivudine in HIV-1 Participants With Suppressed Viremia and Impaired Renal Function (MK-0518-284) Phase 2