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.

Condition	Treatment or Intervention	Phase
HIV Infections	Drug: Zidovudine  Drug: Zalcitabine	Phase III

Further Study Details: 

Expected Total Enrollment:  750

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.

Ages Eligible for Study:  13 Years and above,  Genders Eligible for Study:  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.

California
      Univ of California / San Diego Treatment Ctr, San Diego,  California,  921036325,  United States
      UCSD Med Ctr / Pediatrics / Clinical Sciences, La Jolla,  California,  920930672,  United States
      Sepulveda Veterans Adm Med Ctr / Olive View Med Ctr, Sylmar,  California,  91342,  United States
      Stanford at Kaiser / Kaiser Permanente Med Ctr, San Francisco,  California,  94115,  United States
      Palo Alto Veterans Adm Med Ctr / Stanford Univ, Palo Alto,  California,  94304,  United States
      Stanford Private Practice, Redwood City,  California,  United States
      UCLA CARE Ctr, Los Angeles,  California,  90095,  United States
      Univ of Southern California / LA County USC Med Ctr, Los Angeles,  California,  900331079,  United States
      Harbor UCLA Med Ctr, Torrance,  California,  90502,  United States
      Olive View Med Ctr, Sylmar,  California,  91342,  United States
Colorado
      Univ Hosp / Univ of Colorado Health Sci Ctr, Denver,  Colorado,  80262,  United States
District of Columbia
      George Washington Univ Med Ctr, Washington,  District of Columbia,  20037,  United States
Florida
      Univ of Miami School of Medicine, Miami,  Florida,  331361013,  United States
Indiana
      Indiana Univ Hosp, Indianapolis,  Indiana,  462025250,  United States
Maryland
      Johns Hopkins Hosp, Baltimore,  Maryland,  21287,  United States
Massachusetts
      Harvard (Massachusetts Gen Hosp), Boston,  Massachusetts,  02114,  United States
      Beth Israel Deaconess Med Ctr, Boston,  Massachusetts,  02215,  United States
      Beth Israel Deaconess - West Campus, Boston,  Massachusetts,  02215,  United States
      Boston Med Ctr, Boston,  Massachusetts,  02118,  United States
      Children's Hosp of Boston, Boston,  Massachusetts,  021155724,  United States
      Baystate Med Ctr of Springfield, Springfield,  Massachusetts,  01199,  United States
Minnesota
      Univ of Minnesota, Minneapolis,  Minnesota,  55455,  United States
Missouri
      St Louis Regional Hosp / St Louis Regional Med Ctr, St. Louis,  Missouri,  63112,  United States
New Jersey
      Univ of Medicine & Dentistry of New Jersey / Univ Hosp, Newark,  New Jersey,  071032714,  United States
New York
      Nassau County Med Ctr, East Meadow,  New York,  11554,  United States
      SUNY - Stony Brook, Stony Brook,  New York,  117948153,  United States
      Bellevue Hosp / New York Univ Med Ctr, New York,  New York,  10016,  United States
      Mem Sloan - Kettering Cancer Ctr, New York,  New York,  10021,  United States
      Mount Sinai Med Ctr, New York,  New York,  10029,  United States
      Jack Weiler Hosp / Bronx Municipal Hosp, Bronx,  New York,  10465,  United States
      Cornell Univ Med Ctr, New York,  New York,  10021,  United States
      Saint Luke's - Roosevelt Hosp Ctr, New York,  New York,  10025,  United States
      Bronx Municipal Hosp Ctr/Jacobi Med Ctr, Bronx,  New York,  10461,  United States
      Montefiore Med Ctr / Bronx Municipal Hosp, Bronx,  New York,  10467,  United States
      Bronx Veterans Administration / Mount Sinai Hosp, Bronx,  New York,  10468,  United States
      SUNY / Erie County Med Ctr at Buffalo, Buffalo,  New York,  14215,  United States
      Beth Israel Med Ctr, New York,  New York,  10003,  United States
      City Hosp Ctr at Elmhurst / Mount Sinai Hosp, Elmhurst,  New York,  11373,  United States
      North Central Bronx Hosp / Bronx Municipal Hosp, Bronx,  New York,  10467,  United States
North Carolina
      Univ of North Carolina, Chapel Hill,  North Carolina,  275997215,  United States
      Moses H Cone Memorial Hosp, Greensboro,  North Carolina,  27401,  United States
      Duke Univ Med Ctr, Durham,  North Carolina,  27710,  United States
      Bowman Gray School of Medicine / Wake Forest Univ, Winston Salem,  North Carolina,  27103,  United States
Ohio
      Case Western Reserve Univ, Cleveland,  Ohio,  44106,  United States
      Univ of Cincinnati, Cincinnati,  Ohio,  452670405,  United States
      Ohio State Univ Hosp Clinic, Columbus,  Ohio,  432101228,  United States
      Columbus Children's Hosp, Columbus,  Ohio,  432052696,  United States
      Med College of Ohio, Toledo,  Ohio,  43699,  United States
Pennsylvania
      Univ of Pittsburgh, Pittsburgh,  Pennsylvania,  15213,  United States
South Carolina
      Julio Arroyo, West Columbia,  South Carolina,  29169,  United States
Washington
      Univ of Washington, Seattle,  Washington,  981224304,  United States

Study chairs or principal investigators

M Fischl,  Study Chair
A Collier,  Study Chair

Study ID Numbers:  ACTG 155
Record last reviewed:  January 2003
Last Updated:  April 7, 2005
Record first received:  November 2, 1999
ClinicalTrials.gov Identifier:  NCT00000651
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08