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HIV InfectionsNCT00000718

A Clinical Trial of Alternating and Intermittent Regimens of 2',3'-Dideoxycytidine and 3'-Azido-3'-Deoxythymidine in the Treatment of Patients With AIDS and Advanced ARC

A study testing Zidovudine and Zalcitabine in people with HIV Infections, run by National Institute of Allergy and Infectious Diseases (NIAID) at 1 site 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 if alternating zidovudine (AZT) and zalcitabine (dideoxycytidine; ddC) (first one and then the other) or intermittent therapy (1 week of drug then 1 week off) will lessen the toxic effects of either drug alone, while still inhibiting HIV (the AIDS virus) in patients with AIDS or AIDS related complex. Read more about this study

Who is it for?
Ages 13 years and older
Conditions the study is for
HIV Infections
What is being tested?
Zidovudine and Zalcitabine
How many people
112 participants
Where
1 siteUnited States
Study dates
Start not givento Sep 1991
Phase
Interventional
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 13 years and older
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • Concurrent Medication:
  • Encouraged though not required:
  • Inhaled pentamidine as prophylaxis for Pneumocystis carinii pneumonia (PCP).
  • Allowed:
  • AL-721 use is discouraged but not prohibited.
  • Use of aspirin, acetaminophen, and nonsteroidal anti-inflammatory agents should be minimized, with continuous use for > 72 hours discouraged.
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  • Acute therapy (7 days) with oral acyclovir.
  • Acute therapy with ketoconazole.
  • Concurrent Treatment:
  • Allowed:
  • Up to 4 units of packed red blood cells for hemoglobin toxicity.
  • All patients must have the following:
  • A consistently positive serum HIV p24 antigen = or > 70 pg/ml, defined by the Abbott HIV antigen test, on two occasions. The tests must be within 1 month of study entry, separated by at least 72 hours, and the last must be within 2 weeks of starting therapy. Any negative antigen test during the period will exclude the patient from the study.
  • A positive antibody to HIV confirmed by any federally licensed ELISA test kit.
  • Patients in group A must have AIDS related complex (ARC) as defined by the documented presence of at least one of the following:
  • Recurrent oral candidiasis.
  • Hairy leukoplakia.
  • History of herpes zoster.
  • Temperature > 38.5 degrees C with or without night sweats, persisting for > 14 consecutive days or > 15 days in a 30-day interval prior to study entry.
  • Weight loss of > 15 lbs. or 10 percent of body weight noted in a 120-day period prior to study entry.
  • Diarrhea defined as = or > 3 liquid stools per day, persisting for > 30 days prior to study entry without definable cause.
  • Patients in group B must have CDC-defined AIDS not requiring systemic maintenance chemotherapy.

Who cannot join

  • Co-existing Condition:
  • Patients with the following conditions or symptoms are excluded:
  • Transfusion dependence requiring 2 units of blood more than once per month.
  • Significant malabsorption (> 10 percent weight loss within the past 3 months with serum carotene < 75 IU/ml or vitamin A < 74 IU/ml).
  • Significant cardiac or liver disease.
  • Significant neurologic abnormalities defined by any one of the following:
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  • A significant abnormality on the ddC Neuropathy Targeted Symptom Questionnaire defined as a symptom score > 4 (moderate severity) in any one of six categories or a score > 2 (mild severity) in any two of six categories.
  • Moderate abnormalities on standardized neurologic exam.
  • Any severe abnormality (a value = or > 4.0) on standardized 4-arm quantitative sensory testing of vibration threshold.
  • Diabetes, renal failure, or alcoholism.
  • Dose-limiting or transfusion-requiring toxicity during a previous course of zidovudine therapy.
  • History of idiopathic thrombocytopenic purpura.
  • Requirement for prolonged acyclovir therapy. Patients in group A must not have the following:
  • Opportunistic infection or malignancy fulfilling the CDC definition of AIDS.
  • Neoplasms other than basal cell carcinoma of the skin or in situ carcinoma of the cervix. Patients in group B must not have the following:
  • Active opportunistic infection or AIDS-defining opportunistic infection requiring ongoing systemic therapy and/or prophylaxis other than inhaled pentamidine for Pneumocystis carinii pneumonia prophylaxis.
  • Symptomatic visceral Kaposi's sarcoma (KS), progression of KS within the month prior to study entry.
  • Concurrent neoplasms other than KS, basal cell carcinoma of the skin or in situ carcinoma of the cervix.
  • Concurrent Medication:
  • Excluded:
  • Neurotoxic drugs.
  • Prolonged acyclovir therapy.
  • Antineoplastic therapy.
  • Systemic therapy and/or prophylaxis for an AIDS-defining opportunistic infection, other than inhaled pentamidine for Pneumocystis carinii pneumonia (PCP) prophylaxis.
  • Other antiretroviral agents, immunomodulators, or systemic corticosteroids.
  • Other experimental medication.
  • Concurrent Treatment:
  • Excluded:
  • Transfusion dependency (requiring 2 units of blood more than once per month).
  • Prior Medication:
  • Excluded:
  • Antiretroviral agents within 60 days of study entry.
  • Biologic modifiers or corticosteroids within 30 days prior to study entry.
  • Dideoxycytidine (ddC).
  • Prior Treatment:
  • Excluded:
  • Blood transfusion within 2 weeks of entry.
  • Any negative HIV p24 antigen test during the month prior to entry will exclude the patient from the study.
  • Active drug or alcohol abuse.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Northwestern University CRS

    Chicago, Illinois, 60611

Other trials in United States

About this study

To determine if alternating zidovudine (AZT) and zalcitabine (dideoxycytidine; ddC) (first one and then the other) or intermittent therapy (1 week of drug then 1 week off) will lessen the toxic effects of either drug alone, while still inhibiting HIV (the AIDS virus) in patients with AIDS or AIDS related complex.

AZT extends the survival of some patients with AIDS, and both AZT and ddC are known to inhibit the growth of HIV. When AZT or ddC is given continuously over a prolonged period of time, toxic effects occur that are not found when the drugs are given for 4 - 6 weeks. It is hoped that by alternating the drugs or by giving one drug intermittently, the toxic effects can be decreased without lowering the therapeutic effectiveness of the drugs.

Read the detailed description

AZT extends the survival of some patients with AIDS, and both AZT and ddC are known to inhibit the growth of HIV. When AZT or ddC is given continuously over a prolonged period of time, toxic effects occur that are not found when the drugs are given for 4 - 6 weeks. It is hoped that by alternating the drugs or by giving one drug intermittently, the toxic effects can be decreased without lowering the therapeutic effectiveness of the drugs.

Patients will be assigned to 1 of 7 treatment groups. Both AZT and ddC will be given by mouth every 4 hours. One group will take AZT continuously for 52 weeks. One group will alternate 1 week of AZT with a week with no drug for 48 weeks and another group will alternate 1 week of ddC with a week of no drug for 48 weeks. Other groups will alternate AZT and either low-dose or high-dose ddC on a weekly basis or a monthly basis for 48 weeks. Patients will be seen weekly for the first 8 weeks of study and less often thereafter. Blood samples will be withdrawn frequently and evaluated for possible changes in the immune system, toxic effects, and possible changes in the amount of HIV in the blood. Lumbar punctures and skin biopsies will also be performed.

AMENDED: All patients receiving continuous AZT will be switched to a lower dose of AZT if they have not already been switched. This is in accordance with results of NIAID ACTG 002, 016, and 019 which demonstrate that this dose of AZT delays progression of HIV symptoms.

Conditions
HIV Infections
Being tested
Zidovudine, Zalcitabine
Keywords
Zalcitabine, Dose-Response Relationship, Drug, Acquired Immunodeficiency Syndrome, AIDS-Related Complex, Zidovudine
Medical subject headings
HIV Infections, Acquired Immunodeficiency Syndrome, 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 completionSep 1991

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 N/A
Primary purpose
Treatment
Masking
None (open label)
Enrolment
112 participants
IDs, dates and publications
ClinicalTrials.gov ID
NCT00000718
Sponsor's protocol ID
ACTG 047
Other IDs
11021
Status last verified
Oct 2021
First submitted
2 Nov 1999
Last updated
3 Nov 2021
Results posted
No

Publications

  • Lathey JL, Marschner IC, Kabat B, Spector SA. Deterioration of detectable human immunodeficiency virus serum p24 antigen in samples stored for batch testing. J Clin Microbiol. 1997 Mar;35(3):631-5. doi: 10.1128/jcm.35.3.631-635.1997.

    PubMed 9041402

  • Gries JM, Troconiz IF, Verotta D, Jacobson M, Sheiner LB. A pooled analysis of CD4 response to zidovudine and zalcitabine treatment in patients with AIDS and AIDS-related complex. Clin Pharmacol Ther. 1997 Jan;61(1):70-82. doi: 10.1016/S0009-9236(97)90183-1.

    PubMed 9024175

  • Merigan TC. Treatment of AIDS with combinations of antiretroviral agents. Am J Med. 1991 Apr 10;90(4A):8S-17S. doi: 10.1016/0002-9343(91)90405-m.

    PubMed 1850192

  • Skowron G, Merigan TC. Alternating and intermittent regimens of zidovudine (3'-azido-3'-deoxythymidine) and dideoxycytidine (2',3'-dideoxycytidine) in the treatment of patients with acquired immunodeficiency syndrome (AIDS) and AIDS-related complex. Am J Med. 1990 May 21;88(5B):20S-23S. doi: 10.1016/0002-9343(90)90417-c.

    PubMed 2159705

  • Skowron G, Bozzette SA, Lim L, Pettinelli CB, Schaumburg HH, Arezzo J, Fischl MA, Powderly WG, Gocke DJ, Richman DD, Pottage JC, Antoniskis D, McKinley GF, Hyslop NE, Ray G, Simon G, Reed N, LoFaro ML, Uttamchandani RB, Gelb LD, Sperber SJ, Murphy RL, Leedom JM, Grieco MH, Zachary J, Hirsch MS, Spector SA, Bigley J, Soo W, Merigan TC. Alternating and intermittent regimens of zidovudine and dideoxycytidine in patients with AIDS or AIDS-related complex. Ann Intern Med. 1993 Mar 1;118(5):321-30. doi: 10.7326/0003-4819-118-5-199303010-00001.

    PubMed 8094279

  • Fitzgibbon JE, Howell RM, Schwartzer TA, Gocke DJ, Dubin DT. In vivo prevalence of azidothymidine (AZT) resistance mutations in an AIDS patient before and after AZT therapy. AIDS Res Hum Retroviruses. 1991 Mar;7(3):265-9. doi: 10.1089/aid.1991.7.265.

    PubMed 2064825

Questions about this trial

What is this clinical trial studying?

A study testing Zidovudine and Zalcitabine in people with HIV Infections, run by National Institute of Allergy and Infectious Diseases (NIAID) at 1 site 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 22 inclusion and 39 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 3 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 1 site 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.

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 NCT00000718, 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 3 Nov 2021.

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