Clinical trial NCT00000700: A Multi-Center Clinical Trial To Evaluate Azidothymidine (AZT) in the Treatment of Human Immunodeficiency Virus (HIV) Infection in Patients With AIDS Post First Episode PCP
Official title: A Multi-Center Clinical Trial To Evaluate Azidothymidine (AZT) in the Treatment of Human Immunodeficiency Virus (HIV) Infection in Patients With AIDS Post First Episode PCP
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: HIV Infections
Keywords: United States
AIDS-Related Opportunistic Infections
Pneumonia, Pneumocystis carinii
Acquired Immunodeficiency Syndrome
Zidovudine
Lead sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor class: NIH
First posted: 2001-08-31
Enrollment: 482
Sex: ALL
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: To examine the dose of zidovudine (AZT) that was used in the first placebo-controlled study of AZT in AIDS patients as well as a lower dose of AZT in order to determine if the lower dose results in less harmful side effects while still being effective. Previous studies have shown the effectiveness of AZT in AIDS therapy. AZT has been effective in test tube studies at varying doses. There is a need to see if lower doses result in effective therapy with less harmful side effects.

Detailed description: Previous studies have shown the effectiveness of AZT in AIDS therapy. AZT has been effective in test tube studies at varying doses. There is a need to see if lower doses result in effective therapy with less harmful side effects.

Patients are assigned at random to one of two treatment programs: (1) 1 dose of AZT given orally (PO) for 6 doses per day; (2) 2 doses of AZT PO for 4 weeks followed by 1 dose PO for the remainder of the trial.

Eligibility criteria: Inclusion Criteria

Concurrent Medication:

Allowed:

* All concomitant medication to minimum and record.
* Any approved medications can be used to treat an opportunistic infection.
* Dapsone may be used for Pneumocystis carinii pneumonia (PCP).
* Pyrimethamine - sulfadoxine may be used for toxoplasmosis.
* Ganciclovir for cytomegalovirus may be used for maintenance only.
* Prophylactic therapy for PCP.

Concurrent Treatment:

Allowed:

* Local, limited radiation therapy to isolated Kaposi's sarcoma lesions provided total area is \< 5 x 5 cm and a 6-MeV electron beam or 90 kV x-ray = or \< 3000 rads total is used.

Patients must have:

* HIV seropositivity as confirmed by any federally licensed ELISA test kit.
* Allowed:
* Malignancy in past which has been in complete remission for 1 year without therapy.

Exclusion Criteria

Co-existing Condition:

Patients with active opportunistic infections will be excluded.

Concurrent Medication:

Excluded:

* Aspirin on a regular basis or beyond 72 hours without contacting investigator.
* Cimetidine.
* Flurazepam.
* Indomethacin.
* Ranitidine.
* Probenecid.

Patients with the following are excluded:

* Status post-Pneumocystis carinii pneumonia with symptomatic visceral Kaposi's sarcoma (KS) or progression of KS within the month prior to study entry.
* Other concurrent neoplasms other than basal cell carcinoma of the skin.
* Requiring blood transfusions \> once per month. Last transfusion cannot have been given within 7 days of entry.
* Active substance abuse. Unwilling to sign informed consent or to be followed at medical center where enrolled for duration of study and follow-up if necessary.

Prior Medication:

Excluded within 2 weeks of study entry:

* Treatment for acute Pneumocystis carinii pneumonia (PCP).
* Excluded within 30 days of study entry:
* Other antiretroviral agents, immunomodulating agents, or corticosteroids.

Prior Treatment:

Excluded within 30 days of study entry:

* Radiation therapy or cytotoxic chemotherapy for Kaposi's sarcoma.

Required:

* Patients must be at least 2 weeks post- therapy status for acute Pneumocystis carinii pneumonia (PCP).

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: Miami
country: United States
facility: Univ of Miami School of Medicine
state: Florida
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: Boston
country: United States
facility: Beth Israel Deaconess - West Campus
state: Massachusetts
city: Boston
country: United States
facility: Beth Israel Deaconess Med Ctr
state: Massachusetts
city: Minneapolis
country: United States
facility: Univ of Minnesota
state: Minnesota
city: Bronx
country: United States
facility: Bronx Municipal Hosp Ctr/Jacobi Med Ctr
state: New York
city: Bronx
country: United States
facility: Jack Weiler Hosp / Bronx Municipal Hosp
state: New York
city: Bronx
country: United States
facility: Montefiore Med Ctr / Bronx Municipal Hosp
state: New York
city: Bronx
country: United States
facility: Bronx Veterans Administration / Mount Sinai Hosp
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: 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
city: Pittsburgh
country: United States
facility: Univ of Pittsburgh Med School
state: Pennsylvania
city: Seattle
country: United States
facility: Univ of Washington
state: Washington
Study officials:
name: Fischl M
role: STUDY_CHAIR
References:
citation: Fischl M, Parker CB, Pettinelli C, Wulfsohn M, Rasheed S. The efficacy and safety of a lower dose of zidovudine in the treatment of patients with AIDS-associated PCP. Int Conf AIDS. 1990 Jun 20-23;6(1):138 (abstract no ThB20)
citation: De Gruttola V, Wulfsohn M, Fischl MA, Tsiatis A. Modeling the relationship between survival and CD4 lymphocytes in patients with AIDS and AIDS-related complex. J Acquir Immune Defic Syndr (1988). 1993 Apr;6(4):359-65.
citation: McMahon DK, Winkelstein A, Armstrong JA, Pazin GJ, Hawk H, Ho M. Zidovudine therapy is associated with an increased capacity of phytohemagglutinin-stimulated cells to express interleukin-2 receptors. Pittsburgh AIDS Clinical Trial Unit. AIDS. 1991 May;5(5):491-6. doi: 10.1097/00002030-199105000-00003.
citation: Richman DD, Grimes JM, Lagakos SW. Effect of stage of disease and drug dose on zidovudine susceptibilities of isolates of human immunodeficiency virus. J Acquir Immune Defic Syndr (1988). 1990;3(8):743-6.
citation: Wulfsohn M, Fischl M, Tsiatis A. Predictors of survival among patients with AIDS receiving zidovudine. Int Conf AIDS. 1992 Jul 19-24;8(2):C314 (abstract no PoC 4419)
citation: Rinaldo C, Huang XL, Piazza P, Armstrong J, Rappocciolo G, Pazin G, McMahon D, Gupta P, Fan Z, Zhang Z, et al. Augmentation of cellular immune function during the early phase of zidovudine treatment of AIDS patients. J Infect Dis. 1991 Oct;164(4):638-45. doi: 10.1093/infdis/164.4.638.
citation: Fischl MA, Parker CB, Pettinelli C, Wulfsohn M, Hirsch MS, Collier AC, Antoniskis D, Ho M, Richman DD, Fuchs E, et al. A randomized controlled trial of a reduced daily dose of zidovudine in patients with the acquired immunodeficiency syndrome. The AIDS Clinical Trials Group. N Engl J Med. 1990 Oct 11;323(15):1009-14. doi: 10.1056/NEJM199010113231501.
citation: Unadkat JD, Collier AC, Crosby SS, Cummings D, Opheim KE, Corey L. Pharmacokinetics of oral zidovudine (azidothymidine) in patients with AIDS when administered with and without a high-fat meal. AIDS. 1990 Mar;4(3):229-32. doi: 10.1097/00002030-199003000-00008.
citation: Coombs RW, Collier AC, Allain JP, Nikora B, Leuther M, Gjerset GF, Corey L. Plasma viremia in human immunodeficiency virus infection. N Engl J Med. 1989 Dec 14;321(24):1626-31. doi: 10.1056/NEJM198912143212402.