The Safety and Effectiveness of Hydroxyurea and ddI Used Individually or Together in HIV-Infected Patients
A Phase I/II Dosing Study of the Safety and Antiretroviral Activity of Hydroxyurea Alone and in Combination With ddI Compared With ddI Alone in Subjects With HIV Infection
2 other identifiers
interventional
140
1 country
18
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1 hiv-infections
18 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
November 2, 1999
CompletedStudy Completion
Last participant's last visit for all outcomes
January 1, 2000
CompletedFirst Posted
Study publicly available on registry
August 31, 2001
CompletedNovember 1, 2021
October 1, 2021
November 2, 1999
October 28, 2021
Conditions
Keywords
Interventions
Eligibility Criteria
You may qualify if:
- Concurrent Medication:
- Allowed:
- AS PER AMENDMENT 5/5/97:
- PCP prophylaxis with trimethoprim/sulfamethoxazole or Dapsone.
- Patients must have:
- HIV-1 infection.
- AS PER AMENDMENT 5/5/97:
- CD4 count of 200 - 700 cells/mm3 within 60 days prior to study entry.
- AS PER AMENDMENT 10/1/97:
- HIV RNA plasma level \< 20,000 copies/ml within 60 days of enrollment (obtained at a laboratory certified to perform the Roche Monitor assay).
You may not qualify if:
- Co-existing Condition:
- Patients with any of the following symptoms or conditions are excluded:
- CMV, MAC, toxoplasmosis, or disseminated fungal infection requiring acute or chronic therapy.
- Significant medical illness as determined by investigator.
- Active diagnosis of any malignancy, including visceral Kaposi's sarcoma or extensive cutaneous Kaposi's sarcoma for which systemic chemotherapy is anticipated within the next 24 weeks.
- Current Grade 2 or greater peripheral neuropathy.
- Concurrent Medication:
- Excluded:
- Acute or chronic therapy for CMV, MAC, toxoplasmosis, or disseminated fungal infection.
- AS PER AMENDMENT 5/5/97:
- All antiretroviral medications other than those provided on study.
- Systemic chemotherapy for active malignancies, including systemic treatment for KS.
- Agents with myelosuppressive potential, including tegretol, carboplatin, carmustine, cyclophosphamide and fluorouracil.
- Granulocyte colony stimulating factor (G-CSF) except while hydroxyurea or matching placebo is held.
- Drugs associated with peripheral neuropathy, including:
- +18 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (18)
Univ of California / San Diego Treatment Ctr
San Diego, California, 921036325, United States
Stanford at Kaiser / Kaiser Permanente Med Ctr
San Francisco, California, 94115, United States
Stanford Univ Med Ctr
Stanford, California, 943055107, United States
Harbor UCLA Med Ctr
Torrance, California, 90502, United States
Univ of Colorado Health Sciences Ctr
Denver, Colorado, 80262, United States
Johns Hopkins Hosp
Baltimore, Maryland, 21287, United States
Beth Israel Med Ctr
New York, New York, 10003, United States
Bellevue Hosp / New York Univ Med Ctr
New York, New York, 10016, United States
Mount Sinai Med Ctr
New York, New York, 10029, United States
Univ of North Carolina
Chapel Hill, North Carolina, 275997215, United States
Duke Univ Med Ctr
Durham, North Carolina, 27710, United States
Univ of Cincinnati
Cincinnati, Ohio, 452670405, United States
Case Western Reserve Univ
Cleveland, Ohio, 44106, United States
MetroHealth Med Ctr
Cleveland, Ohio, 441091998, United States
Univ of Pennsylvania at Philadelphia
Philadelphia, Pennsylvania, 19104, United States
Thomas Jefferson Univ Hosp
Philadelphia, Pennsylvania, 191075098, United States
Julio Arroyo
West Columbia, South Carolina, 29169, United States
Univ of Washington
Seattle, Washington, 981224304, United States
Related Publications (2)
Frank I, Boucher H, Fiscus S, Flexner C, Valentine F, Gulick R, Fox L, Eron J. Phase I/II dosing study of once-daily hydroxyurea (HU) alone vs didanosine (ddI) alone vs ddI + HU. Conf Retroviruses Opportunistic Infect. 1999 Jan 31-Feb 4;6th:143 (abstract no 402)
RESULTFrank I, Bosch RJ, Fiscus S, Valentine F, Flexner C, Segal Y, Ruan P, Gulick R, Wood K, Estep S, Fox L, Nevin T, Stevens M, Eron JJ Jr; ACTG 307 Protocol Team. Activity, safety, and immunological effects of hydroxyurea added to didanosine in antiretroviral-naive and experienced HIV type 1-infected subjects: a randomized, placebo-controlled trial, ACTG 307. AIDS Res Hum Retroviruses. 2004 Sep;20(9):916-26. doi: 10.1089/aid.2004.20.916.
PMID: 15597521RESULT
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- STUDY CHAIR
Ian Frank, MD
Division of Infectious Diseases, University of Pennsylvania
- STUDY CHAIR
Joseph Eron, MD
University of North Carolina
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Purpose
- TREATMENT
- Sponsor Type
- NIH
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
November 2, 1999
First Posted
August 31, 2001
Study Completion
January 1, 2000
Last Updated
November 1, 2021
Record last verified: 2021-10