Clinical trial NCT00002427: Safety and Effectiveness of Combining Hydroxyurea (HU) With Didanosine (ddI) and Stavudine (d4T) for Treatment of HIV-Infected Adults
Official title: A Phase I/II Study of the Safety and Antiretroviral Activity of Nine Hydroxyurea Regimens in Combination With ddI and d4T in Subjects With HIV Infection
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: HIV Infections
Keywords: Didanosine
Dose-Response Relationship, Drug
Drug Therapy, Combination
Stavudine
Hydroxyurea
Reverse Transcriptase Inhibitors
Anti-HIV Agents
Lead sponsor: NIH AIDS Clinical Trials Information Service
Sponsor class: INDUSTRY
First posted: 2001-08-31
Enrollment: 225
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Intervention model: FACTORIAL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to compare the safety and effectiveness of 9 doses of HU in order to find the best dose of HU to use with ddI and d4T in fighting HIV infection.

HU plus ddI plus d4T appears to be a suitable anti-HIV drug combination for long-term control of HIV. This combination can sharply decrease viral load (level of HIV in the body) with few side effects, making it easy to take.

Detailed description: The combination of HU plus ddI plus d4T appears to be suitable for long-term control of HIV in that it: (1) has a novel resistance/rebound profile demonstrating virus suppression even in the presence of ddI-resistant mutants; (2) can produce a pronounced fall in viral load; and (3) is well tolerated (over 200 patients have been treated for up to 3 years with minimal side effects).

Patients are stratified by antiretroviral experience: naive (no more than 2 weeks of therapy) versus experienced (more than 2 weeks). Patients must discontinue all antiretroviral therapy for at least 28 days prior to randomization to 1 of 9 HU treatment arms. Treatment arms are divided into 3 HU dose categories: very low, low, and medium. Within each category HU is administered daily on 3 different dosing schedules. Depending on viral load, patients on the very low and low dose arms may have the opportunity to intensify their HU dose at any time beyond Week 12, provided no Grade 3 or 4 HU-related toxicity is present (these patients are monitored for an additional 8 weeks following intensification). All patients receive ddI and d4T at the same doses every day. When 50% of patients have completed 24 weeks of treatment, an analysis is made to determine whether or not to continue the 52-week study without modifications. Patients are monitored periodically for changes in plasma HIV RNA, CD4 cell counts, weight, and symptoms.

Eligibility criteria: Inclusion Criteria

Patients may be eligible for this study if they:

* Are HIV-positive.
* Have a viral load of 5,000 to 100,000 copies/ml.
* Are willing to stop all anti-HIV medications for at least 28 days before receiving study drugs.
* Are at least 18 years old.

Exclusion Criteria

Patients will not be eligible for this study if they:

* Have a history of opportunistic (AIDS-related) infection.
* Have a history of pancreatitis or other serious condition.
* Have any cancer that will require chemotherapy within the next 24 weeks.
* Are allergic to ddI or d4T.
* Have received an HIV vaccine within 28 days of study entry.
* Have received a red blood cell transfusion within the past 60 days, or have had repeated transfusions at any time in the past.
* Abuse alcohol or drugs.
* Have received certain medications.

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: AIDS Healthcare Foundation
state: California
city: San Francisco
country: United States
facility: San Francisco VA Med Ctr
state: California
city: Stamford
country: United States
facility: Gary Blick MD
state: Connecticut
city: Washington
country: United States
facility: Dr Bruce Rashbaum
state: District of Columbia
city: Altamonte Springs
country: United States
facility: IDC Research Initiative
state: Florida
city: Jacksonville
country: United States
facility: Boulevard Comprehensive Care Ctr
state: Florida
city: Tampa
country: United States
facility: Center for Quality Care
state: Florida
city: Atlanta
country: United States
facility: AIDS Research Consortium of Atlanta Inc
state: Georgia
city: Boston
country: United States
facility: New England Med Ctr
state: Massachusetts
city: Albany
country: United States
facility: Albany Med College
state: New York
city: Mt. Vernon
country: United States
facility: Mt Vernon Hosp
state: New York
city: Philadelphia
country: United States
facility: Univ of Pennsylvania Med Ctr
state: Pennsylvania
city: Philadelphia
country: United States
facility: Thomas Jefferson Univ
state: Pennsylvania
city: Mount Pleasant
country: United States
facility: Coastal Carolina Research Ctr
state: South Carolina
city: Dallas
country: United States
facility: Univ of Texas Southwestern Med Ctr of Dallas
state: Texas
city: Galveston
country: United States
facility: Univ of Texas Med Branch
state: Texas
city: Houston
country: United States
facility: Montrose Clinic
state: Texas
city: Seattle
country: United States
facility: Swedish Med Ctr
state: Washington
Study officials:
name: Franco Lori
role: STUDY_CHAIR
name: Julianna Lisziewicz
role: STUDY_CHAIR
References: