The Safety and Effectiveness of Hydroxyurea and ddI Used Individually or Together in HIV-Infected Patients
- Conditions
- HIV Infections
- Registration Number
- NCT00001074
- Brief Summary
To determine the safety and tolerability of hydroxyurea at two doses alone and in combination with didanosine (ddI). To compare the short term antiviral effect of ddI monotherapy versus hydroxyurea plus ddI, as measured by plasma RNA levels at 8 weeks of therapy. \[AS PER AMENDMENT 10/1/97: Accrual to arms involving hydroxyurea alone has been closed.\] Current antiviral therapies for HIV-1 are limited by a few choices, and the lack of sustained clinical benefit from the drugs. The mechanisms that account for the lack of prolonged inhibition of viral replication by these agents are not fully understood. The activity of RT inhibitors might be potentiated by inhibiting host cellular enzymes essential for efficient HIV reverse transcription. Based on this information, comparisons of the antiviral effects of ddI monotherapy and hydroxyurea plus ddI, with the cellular enzyme ribonucleotide reductase as a potential target, should be done.
- Detailed Description
Current antiviral therapies for HIV-1 are limited by a few choices, and the lack of sustained clinical benefit from the drugs. The mechanisms that account for the lack of prolonged inhibition of viral replication by these agents are not fully understood. The activity of RT inhibitors might be potentiated by inhibiting host cellular enzymes essential for efficient HIV reverse transcription. Based on this information, comparisons of the antiviral effects of ddI monotherapy and hydroxyurea plus ddI, with the cellular enzyme ribonucleotide reductase as a potential target, should be done.
This is a 24-week study, with two 12-week treatment periods. Patients are randomized to one of five treatment arms based upon a patient's history of antiretroviral therapy (naive vs. experienced). The five treatment arms are:
1. ddI plus hydroxyurea placebo.
2. hydroxyurea (lower dose) plus ddI placebo for 4 weeks; then hydroxyurea (higher dose) plus ddI.
3. hydroxyurea (higher dose) plus ddI placebo for 4 weeks; then hydroxyurea (higher dose) plus ddI.
4. hydroxyurea (lower dose) plus ddI.
5. hydroxyurea (higher dose) plus ddI. After the completion of week 12, patients on combination therapy remain on their current therapy and patients on ddI plus placebo have hydroxyurea replace the placebo at 1 of 2 assigned doses (1:1 randomization). AS PER AMENDMENT 5/5/97: If after the 24-week treatment period, a patient has an RNA level less than or equal to 5,000 copies/ml or less than 20,000 copies/ml with a greater than 1 log10 decline from baseline, she has the option to continue therapy open-label ddI plus hydroxyurea for an additional 24 weeks.
AS PER AMENDMENT 10/1/97: Accrual to the arms involving hydroxyurea alone has been closed. Patients are randomized to one of the three treatment arms, as follows:
1. hydroxyurea placebo plus ddI.
2. hydroxyurea (lower dose) plus ddI.
3. hydroxyurea (higher dose) plus ddI.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 140
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method
Trial Locations
- Locations (18)
Julio Arroyo
🇺🇸West Columbia, South Carolina, United States
Johns Hopkins Hosp
🇺🇸Baltimore, Maryland, United States
Univ of Colorado Health Sciences Ctr
🇺🇸Denver, Colorado, United States
Beth Israel Med Ctr
🇺🇸New York, New York, United States
Univ of North Carolina
🇺🇸Chapel Hill, North Carolina, United States
Duke Univ Med Ctr
🇺🇸Durham, North Carolina, United States
Univ of Cincinnati
🇺🇸Cincinnati, Ohio, United States
Case Western Reserve Univ
🇺🇸Cleveland, Ohio, United States
Univ of Pennsylvania at Philadelphia
🇺🇸Philadelphia, Pennsylvania, United States
Thomas Jefferson Univ Hosp
🇺🇸Philadelphia, Pennsylvania, United States
Univ of Washington
🇺🇸Seattle, Washington, United States
Mount Sinai Med Ctr
🇺🇸New York, New York, United States
MetroHealth Med Ctr
🇺🇸Cleveland, Ohio, United States
Harbor UCLA Med Ctr
🇺🇸Torrance, California, United States
Stanford at Kaiser / Kaiser Permanente Med Ctr
🇺🇸San Francisco, California, United States
Stanford Univ Med Ctr
🇺🇸Stanford, California, United States
Univ of California / San Diego Treatment Ctr
🇺🇸San Diego, California, United States
Bellevue Hosp / New York Univ Med Ctr
🇺🇸New York, New York, United States