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A Randomized, Double Blind, Comparative Study of Dideoxycytidine (ddC) Alone or ddC/AZT Combination Versus Zidovudine (ZDV) Alone in Patients With HIV Infection Who Have Received Prior ZDV Therapy

Information source: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: HIV Infections

Intervention: Zidovudine (Drug); Zalcitabine (Drug)

Phase: Phase 3

Status: Completed

Sponsored by: National Institute of Allergy and Infectious Diseases (NIAID)

Official(s) and/or principal investigator(s):
M Fischl, Study Chair
A Collier, Study Chair

Summary

To evaluate the safety of zalcitabine (dideoxycytidine; ddC) alone and in combination with zidovudine (AZT) versus AZT alone when administered to asymptomatic patients with a CD4 count = or < 200 cells/mm3 and symptomatic patients with a CD4 count = or < 300 cells/mm3. To compare the effectiveness of ddC alone and in combination with AZT versus AZT alone. ddC has been shown to demonstrate an antiviral effect. AZT has been shown to significantly decrease mortality and reduce the frequency of opportunistic infections in patients with AIDS or advanced ARC. After 1 year of AZT therapy, the effectiveness tends to diminish and patients progress with more opportunistic infections and higher mortality rates. Because of the demonstrated antiviral activity, absence of hematologic toxicity, and lack of cross tolerance in laboratory studies of ddC, a study to investigate the long-term effectiveness of ddC in patients with HIV infection who have received AZT therapy is warranted.

Clinical Details

Official title: A Randomized, Double Blind, Comparative Study of Dideoxycytidine (ddC) Alone or ddC/AZT Combination Versus Zidovudine (ZDV) Alone in Patients With HIV Infection Who Have Received Prior ZDV Therapy

Study design: Masking: Double-Blind, Primary Purpose: Treatment

Detailed description: ddC has been shown to demonstrate an antiviral effect. AZT has been shown to significantly decrease mortality and reduce the frequency of opportunistic infections in patients with AIDS or advanced ARC. After 1 year of AZT therapy, the effectiveness tends to diminish and patients progress with more opportunistic infections and higher mortality rates. Because of the demonstrated antiviral activity, absence of hematologic toxicity, and lack of cross tolerance in laboratory studies of ddC, a study to investigate the long-term effectiveness of ddC in patients with HIV infection who have received AZT therapy is warranted. Patients are randomly assigned to 1 of 3 treatment groups. In study arm 1, patients receive AZT plus ddC placebo. In study arm 2, patients receive ddC plus AZT placebo capsules. In study arm 3, patients receive ddC plus AZT. Patients are seen every other week for first 8 weeks and monthly thereafter. Patients are stratified by HIV disease status, length of time receiving AZT, and systemic or local Pneumocystis carinii pneumonia (PCP) prophylaxis. Patients who reach a clinical AIDS-defining endpoint are offered open-label combination therapy.

Eligibility

Minimum age: 13 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

Inclusion Criteria Concurrent Medication: Required:

- Zidovudine (AZT) = or > 300 mg/day for 6 weeks prior to study entry.

Allowed:

- Chemoprophylaxis for Pneumocystis carinii pneumonia (PCP), candidiasis, and herpes.

- 21 day course of adjuvant systemic corticosteroids for moderate to severe PCP.

- Maintenance treatment with pyrimethamine, sulfadiazine, amphotericin, fluconazole,

ketoconazole, acyclovir, ganciclovir, or medications for tuberculosis or Mycobacterium avium for patients who have recovered from toxoplasmosis, cryptococcosis, candidiasis, herpes virus infections, cytomegalovirus infections, tuberculosis or Mycobacterium avium intracellulare.

- 14 day course of metronidazole.

- Erythropoietin and megace if clinically indicated.

- Isoniazid if patient has no peripheral neuropathy at entry and is taking pyridoxine =

or > 50 mg/day concomitantly.

- Phenytoin if patient has < grade 2 peripheral neuropathy at entry and has been stable

on phenytoin = or > 3 months. Patients must have:

- Ability and willingness to give informed consent.

- Written informed consent from a parent or guardian if < 18 years old.

- Been tolerating zidovudine (AZT) therapy.

- Diagnosis of HIV infection.

Exclusion Criteria Co-existing Condition: Patients with the following conditions or symptoms are excluded:

- Kaposi's sarcoma or other malignancy requiring therapy.

- Active opportunistic infections.

- Peripheral neuropathy as manifested by complaints of moderate pain, burning,

numbness, or tingling in hands/arms or feet/legs; moderate sensory deficit in the upper or lower extremities; or motor weakness in the upper or lower extremities. Concurrent Medication: Excluded:

- Other experimental medications.

- Other anti-HIV drugs.

- Biologic response modifiers.

- Cytotoxic chemotherapy.

- Drugs that could cause peripheral neuropathy including phenytoin not specifically

allowed, hydralazine, nitrofurantoin, vincristine, cisplatinum, dapsone, disulfiram, and diethyldithiocarbamate. Concurrent Treatment: Excluded:

- Radiation therapy.

Patients with the following are excluded:

- Active opportunistic infection. Must have ended acute therapy at least 14 days prior

to study entry.

- Peripheral neuropathy = or > grade 2.

- History of intolerance to 500 to 600 mg/day of zidovudine (AZT) as manifested by the

same recurrent grade 3 toxicity requiring dose interruptions and dose reductions to < 500 mg/day or any prior grade 4 toxicity.

- Prior development of peripheral neuropathy on ddI = or > grade 2.

Prior Medication: Excluded:

- Dideoxycytidine (ddC).

Required:

- Zidovudine (AZT) for total of at least 24 weeks; and included within that time

period, AZT = or > 300 mg/day for 6 weeks prior to the study entry.

Locations and Contacts

UCLA CARE Center CRS, Los Angeles, California 90095, United States

USC CRS, Los Angeles, California 90033, United States

UCSD Maternal, Child, and Adolescent HIV CRS, San Diego, California 92103, United States

Ucsd, Avrc Crs, San Diego, California, United States

Ucsf Aids Crs, San Francisco, California, United States

Harbor-UCLA Med. Ctr. CRS, Torrance, California 90502, United States

University of Colorado Hospital CRS, Aurora, Colorado, United States

Univ. of Miami AIDS CRS, Miami, Florida 33136, United States

Northwestern University CRS, Chicago, Illinois, United States

Rush Univ. Med. Ctr. ACTG CRS, Chicago, Illinois, United States

Indiana Univ. School of Medicine, Infectious Disease Research Clinic, Indianapolis, Indiana 46202, United States

Tulane Hemophilia Treatment Ctr., New Orleans, Louisiana, United States

Tulane Med. Ctr. - Charity Hosp. of New Orleans, ACTU, New Orleans, Louisiana, United States

Johns Hopkins Adult AIDS CRS, Baltimore, Maryland 21287, United States

Beth Israel Deaconess - East Campus A0102 CRS, Boston, Massachusetts 02215, United States

Beth Israel Deaconess Med. Ctr., ACTG CRS, Boston, Massachusetts 02215, United States

Bmc Actg Crs, Boston, Massachusetts 02118, United States

Brigham and Women's Hosp., Div. of Infectious Disease, Boston, Massachusetts, United States

HMS - Children's Hosp. Boston, Div. of Infectious Diseases, Boston, Massachusetts 02115, United States

Massachusetts General Hospital ACTG CRS, Boston, Massachusetts 02114, United States

University of Minnesota, ACTU, Minneapolis, Minnesota 55455, United States

St. Louis ConnectCare, Infectious Diseases Clinic, St Louis, Missouri, United States

Washington U CRS, St Louis, Missouri, United States

NJ Med. School CRS, Newark, New Jersey 07103, United States

SUNY - Buffalo, Erie County Medical Ctr., Buffalo, New York 14215, United States

Beth Israel Med. Ctr. (Mt. Sinai), New York, New York 10029, United States

Cornell University A2201, New York, New York 10021, United States

Memorial Sloan-Kettering Cancer Ctr., New York, New York 10021, United States

NY Univ. HIV/AIDS CRS, New York, New York, United States

NYU Med. Ctr., Dept. of Medicine, New York, New York 10016, United States

Univ. of Rochester ACTG CRS, Rochester, New York, United States

Unc Aids Crs, Chapel Hill, North Carolina 27599, United States

Carolinas HealthCare System, Carolinas Med. Ctr., Charlotte, North Carolina, United States

Duke Univ. Med. Ctr. Adult CRS, Durham, North Carolina 27710, United States

Regional Center for Infectious Disease, Wendover Medical Center CRS, Greensboro, North Carolina, United States

Univ. of Cincinnati CRS, Cincinnati, Ohio 45267, United States

Case CRS, Cleveland, Ohio 44106, United States

The Ohio State Univ. AIDS CRS, Columbus, Ohio 43210, United States

Pitt CRS, Pittsburgh, Pennsylvania 15213, United States

University of Washington AIDS CRS, Seattle, Washington 98122, United States

Additional Information

Click here for more information about Zidovudine

Related publications:

Blum AS, Dal Pan GJ, Feinberg J, Raines C, Mayjo K, Cornblath DR, McArthur JC. Low-dose zalcitabine-related toxic neuropathy: frequency, natural history, and risk factors. Neurology. 1996 Apr;46(4):999-1003.

Fichtenbaum CJ, Clifford DB, Powderly WG. Risk factors for dideoxynucleoside-induced toxic neuropathy in patients with the human immunodeficiency virus infection. J Acquir Immune Defic Syndr Hum Retrovirol. 1995 Oct 1;10(2):169-74.

Fischl M, Collier A, Stanley K, Ardunio JM, Kazial K, Stein D. The safety and efficacy of zidovudine (ZDV) and zalcitabine (ddC) or ddC alone versus ZDV. ACTG 155 Team of the NIAID. Int Conf AIDS. 1993 Jun 6-11;9(1):68 (abstract no WS-B25-1)

Keruly J, Kendig N, Feinberg J, Cotton S, Biggs M, Benjamin Y, Francis H, Wade W, Coplin M, Bartlett J. A model for conducting AIDS clinical trials in a state correctional system. Int Conf AIDS. 1992 Jul 19-24;8(2):B236 (abstract no PoB 3873)

Johnson VA. Combination therapy: more effective control of HIV type 1? AIDS Res Hum Retroviruses. 1994 Aug;10(8):907-12. Review.

Fischl MA, Stanley K, Collier AC, Arduino JM, Stein DS, Feinberg JE, Allan JD, Goldsmith JC, Powderly WG. Combination and monotherapy with zidovudine and zalcitabine in patients with advanced HIV disease. The NIAID AIDS Clinical Trials Group. Ann Intern Med. 1995 Jan 1;122(1):24-32.

Spino C, Kahn JO, Dolin R, Phair JP. Predictors of survival in HIV-infected persons with 50 or fewer CD4 cells/mm3. J Acquir Immune Defic Syndr Hum Retrovirol. 1997 Aug 15;15(5):346-55.

Zackin RA, Clark RA, Currier JS, Mildvan D. Predictive markers of HIV-related weight loss and determination of differences between populations with weight loss stratified by opportunistic processes. J Acquir Immune Defic Syndr. 1999 Oct 1;22(2):189-93.


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Page last updated: August 23, 2015

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