A Comparison of Zidovudine (AZT) Used Alone or in Combination With Didanosine (ddI) or Dideoxycytidine (ddC) in HIV-Infected Patients

NCT ID: NCT00001022

Last Updated: 2021-11-04

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

1200 participants

Study Classification

INTERVENTIONAL

Study Completion Date

1995-12-31

Brief Summary

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Primary: To compare the efficacy of zidovudine ( AZT ) given alone versus AZT plus didanosine ( ddI ) versus AZT plus zalcitabine ( dideoxycytidine; ddC ) in delaying the occurrence of AIDS-related conditions in HIV-infected patients.

Secondary: To compare the frequency and severity of adverse experiences in the three regimens. To compare the mortality rates in the three regimens. To compare the effects of antiretroviral regimens on CD4+ cell levels.

Studies have indicated that maintenance therapy with AZT over extended periods may be limited by dose-dependent toxicity, primarily myelosuppression, and by the emergence of drug-resistant HIV strains. It is anticipated that the combination of AZT with either ddI or ddC may promote higher antiviral efficacy, with acceptable toxicity and less likelihood of development of drug-resistant strains, than AZT alone.

Detailed Description

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Studies have indicated that maintenance therapy with AZT over extended periods may be limited by dose-dependent toxicity, primarily myelosuppression, and by the emergence of drug-resistant HIV strains. It is anticipated that the combination of AZT with either ddI or ddC may promote higher antiviral efficacy, with acceptable toxicity and less likelihood of development of drug-resistant strains, than AZT alone.

Approximately 1200 patients are randomized in a 2:1:1:2 ratio to one of the following four treatment arms: AZT plus ddI, AZT plus ddI placebo, AZT plus ddC placebo, and AZT plus ddC. Average follow-up is 2 years.

Conditions

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HIV Infections

Keywords

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Zalcitabine Didanosine Drug Therapy, Combination Acquired Immunodeficiency Syndrome AIDS-Related Complex Zidovudine

Study Design

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Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Interventions

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Zidovudine

Intervention Type DRUG

Zalcitabine

Intervention Type DRUG

Didanosine

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

Required:

* Documented HIV infection OR working diagnosis of HIV OR evidence of idiopathic suppression with an AIDS-defining opportunistic infection or malignancy (except Kaposi's sarcoma).
* CD4+ cell count = or \< 200/mm3 or = or \< 15 percent of total lymphocyte count within previous 90 days OR history of AIDS-defining opportunistic infection.
* Current PCP prophylaxis.

Exclusion Criteria

Co-existing Condition:

Patients with the following symptoms and conditions are excluded:

* Symptoms of pancreatitis or peripheral neuropathy of grade 2 or worse.
* Requirement for acute therapy for any active AIDS-defining opportunistic infection or systemic chemotherapy for malignancy.
* Stage 2 or worse (moderate) AIDS Dementia Complex.
* Other disorders or conditions for which the study drugs are contraindicated or that may prevent adequate compliance with study therapy.

Concurrent Medication:

Excluded:

* Acute therapy for active AIDS-defining opportunistic infection.
* Systemic chemotherapy for malignancy.
* Antiretroviral therapy other than that provided by this study.

Patients with the following prior conditions are excluded:

* History of pancreatitis or peripheral neuropathy of grade 2 or worse.
* History of intolerance to the study drugs at entry doses and/or frequencies.
* History of phenylketonuria.
Minimum Eligible Age

13 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Institute of Allergy and Infectious Diseases (NIAID)

NIH

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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L Saravolatz

Role: STUDY_CHAIR

D Winslow

Role: STUDY_CHAIR

Locations

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Community Consortium of San Francisco

San Francisco, California, United States

Site Status

Denver CPCRA / Denver Public Hlth

Denver, Colorado, United States

Site Status

Hill Health Corp

New Haven, Connecticut, United States

Site Status

Wilmington Hosp / Med Ctr of Delaware

Wilmington, Delaware, United States

Site Status

Veterans Administration Med Ctr / Regional AIDS Program

Washington D.C., District of Columbia, United States

Site Status

AIDS Research Consortium of Atlanta

Atlanta, Georgia, United States

Site Status

AIDS Research Alliance - Chicago

Chicago, Illinois, United States

Site Status

Louisiana Comm AIDS Rsch Prog / Tulane Univ Med

New Orleans, Louisiana, United States

Site Status

Comprehensive AIDS Alliance of Detroit

Detroit, Michigan, United States

Site Status

Henry Ford Hosp

Detroit, Michigan, United States

Site Status

North Jersey Community Research Initiative

Newark, New Jersey, United States

Site Status

Addiction Research and Treatment Corp

Brooklyn, New York, United States

Site Status

Clinical Directors Network of Region II

New York, New York, United States

Site Status

Harlem AIDS Treatment Group / Harlem Hosp Ctr

New York, New York, United States

Site Status

Portland Veterans Adm Med Ctr / Rsch & Education Grp

Portland, Oregon, United States

Site Status

Richmond AIDS Consortium

Richmond, Virginia, United States

Site Status

Countries

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United States

References

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New trials reach same conclusion: two drugs are better than AZT alone. AIDS Alert. 1995 Nov;10(11):133-6.

Reference Type BACKGROUND
PMID: 11362921 (View on PubMed)

Saravolatz LD, Collins G, Hodges D, Winslow D, Pettinelli C. A randomized, comparative trial of ZDV versus ZDV plus ddI versus ZDV plus ddC in persons with CD4 cell counts of less than 200/mm3. Int Conf AIDS. 1996 Jul 7-12;11(1):21 (abstract no MoB291)

Reference Type BACKGROUND

Ethnicity and treatment. Proj Inf Perspect. 1997 Jul;(22):15-6.

Reference Type BACKGROUND
PMID: 11364573 (View on PubMed)

Besch CL, Morse E, Simon P, Hodges J, Franchino B. Preliminary results of a compliance study within CPCRA 007 combination nucleoside study (NuCombo). Conf Retroviruses Opportunistic Infect. 1997 Jan 22-26;4th:111 (abstract no 254)

Reference Type BACKGROUND

Mayers D, Saravolatz L, Winslow D, Jagodzinski L, Collins G, Hodges D, Pettinelli C, Weislow O, Stein D. Viral burden measurements in CPCRA 007. Int Conf AIDS. 1996 Jul 7-12;11(Program Supplement):16 (abstract no ThB911)

Reference Type BACKGROUND

Kumi J, Collins G, Saravolatz L. Does ethnicity influence the efficacy and toxicity of combination versus monotherapy with nucleosides in AIDS patients? Conf Retroviruses Opportunistic Infect. 1997 Jan 22-26;4th:166 (abstract no 547)

Reference Type BACKGROUND

James JS. AZT, ddI, and ddC combinations at FDA advisory hearing. Food and Drug Administration. AIDS Treat News. 1996 Apr 5;(no 244):6.

Reference Type BACKGROUND
PMID: 11363307 (View on PubMed)

Researchers are rethinking role of AZT in drug therapy. AIDS Policy Law. 1995 Oct 6;10(18):11.

Reference Type BACKGROUND
PMID: 11362821 (View on PubMed)

Saravolatz LD, Winslow DL, Collins G, Hodges JS, Pettinelli C, Stein DS, Markowitz N, Reves R, Loveless MO, Crane L, Thompson M, Abrams D. Zidovudine alone or in combination with didanosine or zalcitabine in HIV-infected patients with the acquired immunodeficiency syndrome or fewer than 200 CD4 cells per cubic millimeter. Investigators for the Terry Beirn Community Programs for Clinical Research on AIDS. N Engl J Med. 1996 Oct 10;335(15):1099-106. doi: 10.1056/NEJM199610103351503.

Reference Type BACKGROUND
PMID: 8813040 (View on PubMed)

Randall P. CPCRA 007: preliminary results of combination antiretroviral study. NIAID AIDS Agenda. 1996 Mar:2.

Reference Type BACKGROUND
PMID: 11363796 (View on PubMed)

Niu F, Zheng C, Liu L. Exploring causal mechanisms and quantifying direct and indirect effects using a joint modeling approach for recurrent and terminal events. Stat Med. 2023 Sep 30;42(22):4028-4042. doi: 10.1002/sim.9846. Epub 2023 Jul 17.

Reference Type DERIVED
PMID: 37461207 (View on PubMed)

Other Identifiers

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11559

Identifier Type: REGISTRY

Identifier Source: secondary_id

CPCRA 007

Identifier Type: -

Identifier Source: org_study_id