Clinical trial NCT00001067: The Effectiveness of Three Anti-HIV Drug Combinations in HIV-Infected Patients Who Have Never Used Anti-HIV Drugs
Official title: A Phase II Randomized Study of the Virologic and Immunologic Effects of Zidovudine Plus Lamivudine (3TC) Versus d4T Versus Zidovudine Plus d4T in HIV-Infected Patients With CD4 Cell Counts Between 300-600/mm3 and No Previous Nucleoside Experience
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: HIV Infections
Keywords: Drug Therapy, Combination
AIDS-Related Complex
Zidovudine
Stavudine
Lamivudine
Lead sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor class: NIH
First posted: 2001-08-31
Enrollment: 105
Sex: ALL
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Primary purpose: TREATMENT

Brief summary: To determine drug efficacy and safety in HIV-infected patients treated with zidovudine ( AZT ) versus stavudine ( d4T ) versus both drugs. Also, to compare short- and long-term changes in magnitude of HIV RNA over time.

Asymptomatic patients with CD4 counts over 300 cells/mm3 are more likely to tolerate any of the nucleoside analogs. d4T, with a favorable toxicity profile and demonstrated anti-HIV activity in previous studies, provides an additional therapeutic option.

Detailed description: Asymptomatic patients with CD4 counts over 300 cells/mm3 are more likely to tolerate any of the nucleoside analogs. d4T, with a favorable toxicity profile and demonstrated anti-HIV activity in previous studies, provides an additional therapeutic option.

Patients are randomized to receive d4T alone, AZT alone, or both in combination for at least 12 weeks. After week 12, 3TC is added to the combination arm. Treatment continues for up to 48 weeks (was a total of 48 weeks, amended 3/26/96).

Eligibility criteria: Inclusion Criteria

Concurrent Medication:

Required:

* TMP / SMX, aerosolized pentamidine, or dapsone for PCP prophylaxis.

Allowed:

* Atovaquone.
* IV pentamidine.
* TMP / SMX.
* Trimetrexate.
* Trimethoprim-dapsone.
* Clindamycin-primaquine.
* Topical antifungals.
* Clotrimazole.
* Ketoconazole.
* Fluconazole.
* Amphotericin B.
* Itraconazole.
* Rifabutin.
* Isoniazid.
* Pyrazinamide.
* Clofazimine.
* Clarithromycin.
* Azithromycin.
* Ethambutol.
* Amikacin.
* Ciprofloxacin.
* Ofloxacin.
* Pyrimethamine.
* Sulfadiazine.
* Clindamycin.
* Filgrastim ( G-CSF ).
* Up to 1000 mg/day acyclovir.
* Erythropoietin.
* Antibiotics.
* Antipyretics.
* Analgesics.
* Antiemetics.
* Rifampin.

Concurrent Treatment:

Allowed:

* Local radiation therapy.

Patients must have:

* HIV infection.
* CD4 count 300 - 600 cells/mm3.
* NO history of AIDS.
* NO active opportunistic infection.
* NO prior nucleoside therapy.
* Life expectancy at least 2 years.

Exclusion Criteria

Co-existing Condition:

Patients with the following symptoms or conditions are excluded:

* Serious underlying medical condition other than HIV such that life expectancy is less than 2 years.
* Malignancy requiring systemic cytotoxic chemotherapy.
* Active grade 2 or worse peripheral neuropathy.

Concurrent Medication:

Excluded:

* Antiretrovirals other than study drugs.
* Systemic cytotoxic chemotherapy.
* Foscarnet.

Patients with the following prior conditions are excluded:

* Chronic diarrhea defined as three or more stools per day for 15 days, within 30 days prior to study entry.
* Unexplained temperature \>= 38.5 C for any 7 days within 30 days prior to study entry.
* Active participation in other experimental therapy within 30 days prior to study entry.

Prior Medication:

Excluded:

* Prior nucleoside antiretrovirals of 1 week or longer duration.
* Any antiretroviral within 90 days prior to study entry.
* Non-nucleoside reverse transcriptase inhibitors and protease inhibitors within 30 days prior to study entry.
* Biologic response modifiers such as IL-2 and interferon within 30 days prior to study entry.

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Alabama Therapeutics CRS
state: Alabama
city: Palo Alto
country: United States
facility: Stanford CRS
state: California
city: San Diego
country: United States
facility: Ucsd, Avrc Crs
state: California
city: Washington
country: United States
facility: Howard University Hosp., Div. of Infectious Diseases, ACTU
state: District of Columbia
city: Atlanta
country: United States
facility: The Ponce de Leon Ctr. CRS
state: Georgia
city: Baltimore
country: United States
facility: Johns Hopkins Adult AIDS CRS
state: Maryland
city: Saint Louis
country: United States
facility: Washington U CRS
state: Missouri
city: Saint Louis
country: United States
facility: St. Louis ConnectCare, Infectious Diseases Clinic
state: Missouri
city: New York
country: United States
facility: Beth Israel Med. Ctr. (Mt. Sinai)
state: New York
city: New York
country: United States
facility: NYU Med. Ctr., Dept. of Medicine
state: New York
city: Chapel Hill
country: United States
facility: Unc Aids Crs
state: North Carolina
city: Columbus
country: United States
facility: The Ohio State Univ. AIDS CRS
state: Ohio
city: San Juan
country: Puerto Rico
facility: Puerto Rico-AIDS CRS
Study officials:
name: Havlir D
role: STUDY_CHAIR
name: Pollard R
role: STUDY_CHAIR
name: Richman D
role: STUDY_CHAIR
name: Friedland G
role: STUDY_CHAIR
References:
citation: Cadman J. 2, 4, 6, 8, who's afraid to phosphorylate? GMHC Treat Issues. 1998 Feb;12(2):6-8.
citation: Havlir DV, Friedland G, Pollard R, Tierney C, Smeaton L, Fox L, Richman DD. Combination zidovudine (ZDV) and stavudine (d4T) therapy versus other nucleosides: report of two randomized trials (ACTG 290 and 298). Conf Retroviruses Opportunistic Infect. 1998 Feb 1-5;5th:79 (abstract no 2)
citation: Pollard RB, Tierney C, Havlir D, Tebas P, Fox L, Smeaton L, Richman D, Friedland GH. A phase II randomized study of the virologic and immunologic effect of zidovudine + stavudine versus stavudine alone and zidovudine + lamivudine in patients with >300 CD4 cells who were antiretroviral naive (ACTG 298). AIDS Res Hum Retroviruses. 2002 Jul 1;18(10):699-704. doi: 10.1089/088922202760072311.