Clinical trial NCT00000994: A Study of AZT in HIV-Infected Patients With AIDS-Related Kaposi's Sarcoma
Official title: A Placebo-Controlled Trial To Evaluate Azidothymidine (AZT) in the Treatment of Human Immunodeficiency Virus (HIV) Infection in Patients With AIDS-Associated Kaposi's Sarcoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: HIV Infections
Keywords: AIDS-Related Opportunistic Infections
Sarcoma, Kaposi
Acquired Immunodeficiency Syndrome
Zidovudine
Lead sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor class: NIH
First posted: 2001-08-31
Enrollment: 240
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Primary purpose: TREATMENT

Brief summary: To determine whether taking zidovudine (AZT) will change the natural course of HIV infection in patients with AIDS-associated Kaposi's sarcoma (KS) and whether administering AZT at a similar dose but at different intervals will reduce toxicity in a more manageable treatment plan.

Patients infected with AIDS can benefit from therapy with an effective anti-AIDS virus agent. AZT is a drug that is effective in inhibiting the effects of HIV infection. The study will show whether toxicity of AZT can be reduced in a more manageable treatment plan, and whether AZT therapy will delay the development of opportunistic infections and/or KS lesions.

Detailed description: Patients infected with AIDS can benefit from therapy with an effective anti-AIDS virus agent. AZT is a drug that is effective in inhibiting the effects of HIV infection. The study will show whether toxicity of AZT can be reduced in a more manageable treatment plan, and whether AZT therapy will delay the development of opportunistic infections and/or KS lesions.

Patients are divided into two treatment groups, the first receiving AZT for 5 doses a day, and the second receiving AZT for 3 doses per day. A placebo group is divided into two to match the two treatment groups. Study patients are stratified according to whether they have (a) 10 or fewer cutaneous lesions without oral lesions or (b) more extensive cutaneous lesions or oral lesions. Patients are seen on an outpatient basis weekly for the first 2 months, every other week for the next 2 months, and monthly thereafter.

Eligibility criteria: Inclusion Criteria

Concurrent Medication:

Allowed:

* Acute treatment for mucocutaneous candidiasis, localized cutaneous herpes simplex, or localized or disseminated zoster infections.

Concurrent Treatment:

Allowed:

* Blood transfusion for treatment of Grade 3 hemoglobin toxicity if the patient's cardiovascular status is compromised or if the hemoglobin fails to show signs of recovery following withdrawal from the study drug. Toxicity grades according to NIAID Recommendations for Grading Acute and Subacute Toxic Effects (Adults).

Patients must have:

* HIV-related, biopsy-proven Kaposi's sarcoma mucocutaneous lesions without constitutional symptoms.

Exclusion Criteria

Co-existing Condition:

Patients with the following conditions will be excluded:

* Symptomatic, visceral Kaposi's sarcoma.
* Lymphedema.
* HIV neurologic disease as determined by a standard neurologic examination and neuropsychological questionnaire.

Concurrent Medication:

Excluded:

* Aspirin or acetaminophen on a regular basis or for longer than 72 hours without approval of investigator.
* Cimetidine.
* Flurazepam.
* Indomethacin.
* Ranitidine.
* Probenecid.
* Drugs causing anemia, neutropenia, or significant risk of nephrotoxicity.
* Prophylaxis or chronic suppression of herpes simplex.
* Treatment of herpes simplex virus cutaneous disease more often than once a month for 5 - 7 days.

Concurrent Treatment:

Excluded:

* Radiation therapy for treatment of Kaposi's sarcoma lesions.

The following patients will be excluded from the study:

* Patients with a history of any AIDS-defining opportunistic infection.
* Patients with any of the following constitutional symptoms with no etiology established:
* Temperature more than 38 degrees and/or drenching night sweats for more than 1 month; watery diarrhea for 2 or more weeks; weight loss of more than 10 percent.
* Patients with a history of other systemic malignancies or lymphomas.

Prior Medication:

Excluded:

* Systemic antineoplastic chemotherapy.
* Zidovudine (AZT).
* Excluded within 30 days of study entry:
* Antiretroviral agents.
* Immunomodulating agents.
* Prophylaxis for Pneumocystis carinii pneumonia.
* Prophylaxis for herpes simplex virus infections.
* Any other experimental therapy.

Prior Treatment:

Excluded within 30 days of study entry:

* Any experimental therapy.
* Active substance abuse.

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Los Angeles County - USC Med Ctr
state: California
city: Los Angeles
country: United States
facility: UCLA CARE Ctr
state: California
city: San Diego
country: United States
facility: Univ of California / San Diego Treatment Ctr
state: California
city: San Francisco
country: United States
facility: San Francisco AIDS Clinic / San Francisco Gen Hosp
state: California
city: San Francisco
country: United States
facility: Stanford at Kaiser / Kaiser Permanente Med Ctr
state: California
city: Stanford
country: United States
facility: Stanford Univ School of Medicine
state: California
city: New Orleans
country: United States
facility: Charity Hosp / Tulane Univ Med School
state: Louisiana
city: New Orleans
country: United States
facility: Louisiana State Univ Med Ctr / Tulane Med School
state: Louisiana
city: New Orleans
country: United States
facility: Tulane Univ School of Medicine
state: Louisiana
city: Baltimore
country: United States
facility: Johns Hopkins Hosp
state: Maryland
city: Boston
country: United States
facility: Harvard (Massachusetts Gen Hosp)
state: Massachusetts
city: Minneapolis
country: United States
facility: Univ of Minnesota
state: Minnesota
city: Bronx
country: United States
facility: Bronx Veterans Administration / Mount Sinai Hosp
state: New York
city: Buffalo
country: United States
facility: SUNY / Erie County Med Ctr at Buffalo
state: New York
city: Elmhurst
country: United States
facility: City Hosp Ctr at Elmhurst / Mount Sinai Hosp
state: New York
city: New York
country: United States
facility: Beth Israel Med Ctr / Peter Krueger Clinic
state: New York
city: New York
country: United States
facility: Bellevue Hosp / New York Univ Med Ctr
state: New York
city: New York
country: United States
facility: Mem Sloan - Kettering Cancer Ctr
state: New York
city: New York
country: United States
facility: Mount Sinai Med Ctr
state: New York
city: Rochester
country: United States
facility: Univ of Rochester Medical Center
state: New York
city: Syracuse
country: United States
facility: SUNY / State Univ of New York
state: New York
city: Durham
country: United States
facility: Duke Univ Med Ctr
state: North Carolina
Study officials:
name: Valentine FT
role: STUDY_CHAIR
References:
citation: Chaisson RE, Fuchs E, Stanton DL, Quinn TC, Hendricksen C, Bartlett JG, Farzadegan H. Racial heterogeneity of HIV antigenemia in people with HIV infection. AIDS. 1991 Feb;5(2):177-80. doi: 10.1097/00002030-199102000-00007.