Safety and Effectiveness of Combining Hydroxyurea (HU) With Didanosine (ddI) and Stavudine (d4T) for Treatment of HIV-Infected Adults

HIV Infections Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00002427
• Other study ID #: 304A
• Secondary ID: RIGHT 702
• Status: Completed
• Phase: Phase 1
• First received: November 2, 1999
• Last updated: June 23, 2005
• Start date: May 1999

Study information

• Verified date: August 2000
• Source: NIH AIDS Clinical Trials Information Service
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 225
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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.

Study Design

Endpoint Classification: Safety Study, Intervention Model: Factorial Assignment, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Acquired Immunodeficiency Syndrome
• HIV Infections

Intervention

Drug:
• Hydroxyurea

• Stavudine

• Didanosine

Locations

Country	Name	City	State
United States	Albany Med College	Albany	New York
United States	IDC Research Initiative	Altamonte Springs	Florida
United States	AIDS Research Consortium of Atlanta Inc	Atlanta	Georgia
United States	New England Med Ctr	Boston	Massachusetts
United States	Univ of Texas Southwestern Med Ctr of Dallas	Dallas	Texas
United States	Univ of Texas Med Branch	Galveston	Texas
United States	Montrose Clinic	Houston	Texas
United States	Boulevard Comprehensive Care Ctr	Jacksonville	Florida
United States	AIDS Healthcare Foundation	Los Angeles	California
United States	Coastal Carolina Research Ctr	Mount Pleasant	South Carolina
United States	Mt Vernon Hosp	Mt. Vernon	New York
United States	Thomas Jefferson Univ	Philadelphia	Pennsylvania
United States	Univ of Pennsylvania Med Ctr	Philadelphia	Pennsylvania
United States	San Francisco VA Med Ctr	San Francisco	California
United States	Swedish Med Ctr	Seattle	Washington
United States	Gary Blick MD	Stamford	Connecticut
United States	Center for Quality Care	Tampa	Florida
United States	Dr Bruce Rashbaum	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
Research Institute for Genetic and Human Therapy

Country where clinical trial is conducted

United States,