AzTrials
AzTrials

HIV InfectionsPhase 2NCT00001063

The Effectiveness of Three Drug Combinations in HIV-Infected Patients Who Have Taken Zidovudine for More Than 12 Weeks

A Phase 2 study testing Stavudine, Zidovudine and Didanosine in people with HIV Infections, run by National Institute of Allergy and Infectious Diseases (NIAID) at 33 sites in 2 countries.

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 compare the effect of stavudine (d4T) alone or with zidovudine (AZT) versus didanosine (ddI) alone or with AZT on CD4 counts, HIV RNA levels, and viral load in HIV-infected patients [AS PER AMENDMENT 3/21/97: To compare the effects of d4T alone versus ddI alone versus AZT plus ddI]. Read more about this study

Who is it for?
Ages 12 years and older
Conditions the study is for
HIV Infections
What is being tested?
Stavudine, Zidovudine and Didanosine
How many people
200 participants
Where
33 sitesin 2 countries
Study dates
Start not givento Nov 1997
Phase
Phase 2
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 12 years and older
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • Concurrent Medication:
  • Required for patients whose CD4 count falls below 200 cells/mm3:
  • PCP prophylaxis with TMP/SMX, aerosolized pentamidine, or dapsone.
  • Allowed:
  • Atovaquone, IV pentamidine, trimethoprim-dapsone, clindamycin-primaquine, trimetrexate, or TMP/SMX for acute PCP.
  • Topical antifungals, clotrimazole, ketoconazole, fluconazole, and amphotericin B for mucosal and esophageal candidiasis.
Show all 43Show fewer
  • Itraconazole.
  • Amphotericin B.
  • Rifabutin.
  • Isoniazid.
  • Pyrazinamide.
  • Clofazimine.
  • Clarithromycin.
  • Azithromycin.
  • Ethambutol.
  • Amikacin.
  • Ciprofloxacin.
  • Ofloxacin.
  • Pyrimethamine.
  • Sulfadiazine.
  • Clindamycin.
  • Ganciclovir.
  • G-CSF.
  • Acyclovir (up to 1000 mg/day).
  • Erythropoietin.
  • Antibiotics for bacterial infections.
  • Antipyretics.
  • Analgesics.
  • Antiemetics.
  • Rifampin.
  • Concurrent Treatment:
  • Allowed:
  • Local radiation therapy.
  • Patients must have:
  • HIV infection.
  • CD4 count 300-600 cells/mm3.
  • More than 12 weeks (was 24 weeks, AMENDED 3/31/96) of total prior AZT ( > 500 mg/day without serious adverse event). Subjects must be actively taking ZDV for at least 4 continuous weeks up to the time of study entry.
  • No prior or current history of AIDS.
  • No active opportunistic infection.
  • Life expectancy of at least 2 years.
  • Consent of patient and parent or guardian if less than 18 years of age.
  • NOTE:
  • Protocol is approved for prisoner enrollment.

Who cannot join

  • Co-existing Condition:
  • Patients with the following symptoms or conditions are excluded:
  • Malignancy requiring systemic cytotoxic chemotherapy.
  • Serious underlying medical condition other than HIV that would reduce life expectancy to < 2 years.
  • Concurrent Medication:
  • Excluded:
Show all 20Show fewer
  • Antiretrovirals other than study drugs.
  • Foscarnet.
  • Patients with the following prior conditions are excluded:
  • Unexplained temperature >= 38.5 C for 7 days or chronic diarrhea (>= three stools daily) for 15 days, if occurring within 30 days prior to study entry.
  • History of acute or chronic pancreatitis.
  • History of grade 2 or higher peripheral neuropathy.
  • History of grade 3 or worse intolerance to 500-600 mg/day AZT.
  • Prior Medication:
  • Excluded:
  • (within 30 days prior to study entry)
  • Prior ddI, ddC, 3TC or d4T (more than 2 weeks total).
  • Non-nucleoside reverse transcriptase inhibitor or protease inhibitor.
  • Biologic response modifiers such as interferon and IL-2.
  • Other experimental therapy.

Trial locations and contacts

33 sites in 2 countries.

33 sites in 2 countries

United States31 sites

  • University of Colorado Hospital CRS

    Aurora, Colorado, 80262

  • Massachusetts General Hospital ACTG CRS

    Boston, Massachusetts, 02114

  • Bmc Actg Crs

    Boston, Massachusetts, 02118

  • Beth Israel Deaconess Med. Ctr., ACTG CRS

    Boston, Massachusetts, 02215

  • SUNY Downstate Med. Ctr., Children's Hosp. at Downstate NICHD CRS

    Brooklyn, New York, 11203

  • SUNY - Buffalo, Erie County Medical Ctr.

    Buffalo, New York, 14215

  • Northwestern University CRS

    Chicago, Illinois, 60611

  • Cook County Hosp. CORE Ctr.

    Chicago, Illinois, 60612

  • Rush Univ. Med. Ctr. ACTG CRS

    Chicago, Illinois, 60612

  • Weiss Memorial Hosp.

    Chicago, Illinois

  • Univ. of Cincinnati CRS

    Cincinnati, Ohio

  • The Ohio State Univ. AIDS CRS

    Columbus, Ohio, 43210

  • Univ. of Hawaii at Manoa, Leahi Hosp.

    Honolulu, Hawaii, 96816

  • Indiana Univ. School of Medicine, Infectious Disease Research Clinic

    Indianapolis, Indiana, 46202

  • Indiana Univ. School of Medicine, Wishard Memorial

    Indianapolis, Indiana, 46202

  • Methodist Hosp. of Indiana

    Indianapolis, Indiana, 46202

  • Univ. of Florida Jacksonville NICHD CRS

    Jacksonville, Florida, 32209

  • UCLA CARE Center CRS

    Los Angeles, California, 90095

  • Univ. of Miami AIDS CRS

    Miami, Florida, 33136

  • Hennepin County Med. Ctr., Div. of Infectious Diseases

    Minneapolis, Minnesota, 55415

  • University of Minnesota, ACTU

    Minneapolis, Minnesota

  • Tulane Hemophilia Treatment Ctr.

    New Orleans, Louisiana, 70112

  • Stanford CRS

    Palo Alto, California, 94115

  • Univ. of Rochester ACTG CRS

    Rochester, New York, 14642

  • Ucsd, Avrc Crs

    San Diego, California, 92103

  • Ucsf Aids Crs

    San Francisco, California, 94110

  • University of Washington AIDS CRS

    Seattle, Washington, 98122

  • St. Louis ConnectCare, Infectious Diseases Clinic

    St Louis, Missouri, 63112

  • Washington U CRS

    St Louis, Missouri

  • Harbor-UCLA Med. Ctr. CRS

    Torrance, California, 90502

  • Children's National Med. Ctr., ACTU

    Washington D.C., District of Columbia, 20010

Other trials in United States

Puerto Rico2 sites

  • San Juan City Hosp. PR NICHD CRS

    San Juan, 00936

  • Puerto Rico-AIDS CRS

    San Juan

Other trials in Puerto Rico

About this study

Official title: A Phase II Randomized Study of the Virologic and Immunologic Effects of d4T vs Zidovudine Plus d4T vs Zidovudine Plus Ddl in HIV-Infected Patients With CD4 Cell Counts Between 300-600/mm3 and Greater Than 12 Weeks Zidovudine Experience

To compare the effect of stavudine (d4T) alone or with zidovudine (AZT) versus didanosine (ddI) alone or with AZT on CD4 counts, HIV RNA levels, and viral load in HIV-infected patients [AS PER AMENDMENT 3/21/97: To compare the effects of d4T alone versus ddI alone versus AZT plus ddI]. To compare the safety of d4T/AZT. AS PER AMENDMENT 3/21/97: To evaluate the pharmacokinetic interactions of AZT and d4T both at an extracellular and intracellular level.

Although AZT and ddI can delay the advancement of HIV disease, the benefit of either of these drugs has proven to be only temporary. d4T, a new nucleoside analog with a favorable toxicity profile and demonstrated activity against HIV, offers an additional therapeutic option. It is reasonably assumed that the benefit of an antiretroviral agent in terms of delaying clinical disease progression is directly related to its ability to achieve and sustain viral suppression; thus, this study measures effects on viral load and CD4 count.

Read the detailed description

Although AZT and ddI can delay the advancement of HIV disease, the benefit of either of these drugs has proven to be only temporary. d4T, a new nucleoside analog with a favorable toxicity profile and demonstrated activity against HIV, offers an additional therapeutic option. It is reasonably assumed that the benefit of an antiretroviral agent in terms of delaying clinical disease progression is directly related to its ability to achieve and sustain viral suppression; thus, this study measures effects on viral load and CD4 count.

Patients are randomized in a blinded fashion to receive AZT or placebo in combination with open-label d4T or ddI for up to 48 weeks. AS PER AMENDMENT 3/21/97: The study is now composed of three arms: open-label d4T versus open-label ddI plus blinded AZT placebo versus blinded AZT plus open-label ddI. Patients originally assigned to the d4T + AZT arm, which was closed 10/96, will be given the option of discontinuing AZT and remaining on d4T monotherapy or discontinuing all study drugs. In addition, all study participants will be asked to participate in a pharmacology substudy.

Conditions
HIV Infections
Being tested
Stavudine, Zidovudine, Didanosine
Keywords
Didanosine, Drug Therapy, Combination, AIDS-Related Complex, Zidovudine, Stavudine
Medical subject headings
HIV Infections, AIDS-Related Complex

What participants receive

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

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 completionNov 1997

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 2
Primary purpose
Treatment
Enrolment
200 participants
IDs, dates and publications
ClinicalTrials.gov ID
NCT00001063
Sponsor's protocol ID
ACTG 290
Other IDs
11266
Status last verified
Oct 2021
First submitted
2 Nov 1999
Last updated
4 Nov 2021
Results posted
No

Publications

  • d4T+AZT--unexpected CD4 drop seen in study. AIDS Treat News. 1996 Dec 20;(No 261):1.

    PubMed 11364024

  • Shaefer M, Hardy WD, Shaker-Irwin L, Williams V, Maude C, Thommes J, Graham N. HIV viral load response in subjects switched from zidovudine (ZDV)-containing to stavudine (D4T)-containing regimens in the Pacific Oaks Population Study (POPS). Int Conf AIDS. 1998;12:57 (abstract no 12228)

  • Havlir DV, Friedland G, Pollard R, Tierney C, Smeaton L, Fox L, Richman DD. Combination zidovudine (ZDV) and stavudine (d4T) therapy versus other nucleosides: report of two randomized trials (ACTG 290 and 298). Conf Retroviruses Opportunistic Infect. 1998 Feb 1-5;5th:79 (abstract no 2)

  • Cadman J. 2, 4, 6, 8, who's afraid to phosphorylate? GMHC Treat Issues. 1998 Feb;12(2):6-8.

    PubMed 11365218

  • Havlir DV, Tierney C, Friedland GH, Pollard RB, Smeaton L, Sommadossi JP, Fox L, Kessler H, Fife KH, Richman DD. In vivo antagonism with zidovudine plus stavudine combination therapy. J Infect Dis. 2000 Jul;182(1):321-5. doi: 10.1086/315683. Epub 2000 Jul 6.

    PubMed 10882616

  • Sommadossi JP, Zhou XJ, Moore J, Havlir DV, Friedland G, Tierney C, Smeaton L, Fox L, Richman D, Pollard R. Impairment of stavudine (d4T) phosphorylation in patients receiving a combination of zidovudine (ZDV) and d4T (ACTG 290). Conf Retroviruses Opportunistic Infect. 1998 Feb 1-5;5th:79 (abstract no 3)

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Stavudine, Zidovudine and Didanosine in people with HIV Infections, run by National Institute of Allergy and Infectious Diseases (NIAID) at 33 sites in 2 countries.

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 43 inclusion and 20 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 4 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 33 sites in United States, Puerto Rico. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

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 NCT00001063, which also lists 6 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 4 Nov 2021.

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