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HIV InfectionsPhase 1NCT00001074

The Safety and Effectiveness of Hydroxyurea and ddI Used Individually or Together in HIV-Infected Patients

A Phase 1 study testing Hydroxyurea and Didanosine in people with HIV Infections, run by National Institute of Allergy and Infectious Diseases (NIAID) at 18 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
HIV Infections
What is being tested?
Hydroxyurea and Didanosine
How many people
140 participants
Where
18 sitesUnited States
Study dates
Start not givento Jan 2000
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Concurrent Medication:
  • Allowed:
  • AS PER AMENDMENT 5/5/97:
  • PCP prophylaxis with trimethoprim/sulfamethoxazole or Dapsone.
  • Patients must have:
  • HIV-1 infection.
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  • 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).

Who cannot join

  • 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.
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  • 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:
  • hydralazine, disulfiram, nitrofurantoin, cisplatinum, diethyldithiocarbamate, gold, rifampin, chloramphenicol, clioquinol, ethambutol, ethionamide, glutethimide, sodium cyanate, and thalidomide.
  • Patients with any of the prior conditions are excluded:
  • History of transfusion dependent anemia, defined as any history of repeated transfusion with two or more units of red blood cells.
  • At the discretion of the investigator, history of pancreatitis.
  • Prior Medication:
  • Excluded:
  • More than 2 weeks prior treatment with ddI.
  • AS PER AMENDMENT 5/5/97:
  • Other antiretrovirals must be discontinued at least 14 days prior to randomization.
  • Prior hydroxyurea.
  • Any candidate HIV vaccine or agent with potential immune modulating effects within the past 30 days.
  • Any colony stimulating factor or erythropoietin within the past 60 days.
  • Prior Treatment:
  • Excluded:
  • Transfusion with red blood cells within the past 60 days.
  • Risk Behavior:
  • Excluded:
  • At the investigator's discretion, any active substance abuse, including alcohol abuse interfering with compliance.

Trial locations and contacts

18 sites in 1 country.

18 sites in 1 country

United States18 sites

  • Johns Hopkins Hosp

    Baltimore, Maryland, 21287

  • Univ of North Carolina

    Chapel Hill, North Carolina, 275997215

  • Univ of Cincinnati

    Cincinnati, Ohio, 452670405

  • Case Western Reserve Univ

    Cleveland, Ohio, 44106

  • MetroHealth Med Ctr

    Cleveland, Ohio, 441091998

  • Univ of Colorado Health Sciences Ctr

    Denver, Colorado, 80262

  • Duke Univ Med Ctr

    Durham, North Carolina, 27710

  • Beth Israel Med Ctr

    New York, New York, 10003

  • Bellevue Hosp / New York Univ Med Ctr

    New York, New York, 10016

  • Mount Sinai Med Ctr

    New York, New York, 10029

  • Univ of Pennsylvania at Philadelphia

    Philadelphia, Pennsylvania, 19104

  • Thomas Jefferson Univ Hosp

    Philadelphia, Pennsylvania, 191075098

  • Univ of California / San Diego Treatment Ctr

    San Diego, California, 921036325

  • Stanford at Kaiser / Kaiser Permanente Med Ctr

    San Francisco, California, 94115

  • Univ of Washington

    Seattle, Washington, 981224304

  • Stanford Univ Med Ctr

    Stanford, California, 943055107

  • Harbor UCLA Med Ctr

    Torrance, California, 90502

  • Julio Arroyo

    West Columbia, South Carolina, 29169

Other trials in United States

About this study

Official title: 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

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.

Read the 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.
Conditions
HIV Infections
Being tested
Hydroxyurea, Didanosine
Keywords
Didanosine, Drug Therapy, Combination, Antiviral Agents, Hydroxyurea
Medical subject headings
HIV Infections

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • HydroxyureaDrug

  • DidanosineDrug

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted31 Aug 2001 (estimated)
  2. Study completionJan 2000

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Enrolment
140 participants
IDs, dates and publications
ClinicalTrials.gov ID
NCT00001074
Sponsor's protocol ID
ACTG 307
Other IDs
11282
Status last verified
Oct 2021
First submitted
2 Nov 1999
Last updated
1 Nov 2021
Results posted
No

Publications

  • 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)

  • Frank 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.

    PubMed 15597521

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Hydroxyurea and Didanosine in people with HIV Infections, run by National Institute of Allergy and Infectious Diseases (NIAID) at 18 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 10 inclusion and 33 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 1 Nov 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 18 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00001074, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Nov 2021.

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