A Randomized, Unblinded Trial of Zidovudine Versus ddC in the Treatment of Patients Status Post PCP Who Received Long-Term Zidovudine Therapy in Protocol ACTG 002

Study Description

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Brief Summary:

To evaluate the efficacy of AZT versus ddC in terms of survival, antiviral effects, neurological status, and health status in patients post Pneumocystis carinii pneumonia (PCP) who received long-term AZT therapy in ACTG protocol 002 While treatment with AZT has been found to be effective in prolonging survival and reducing the numbers of opportunistic infections in patients with AIDS, during the second year of administration of AZT an acceleration in mortality has been observed. The reasons for this are not known at this time. The study of what may be an AZT-resistant strain of HIV may benefit patients who have been and are still receiving AZT or another drug used in treating HIV ddC. It is hoped that the comparison of the effectiveness of AZT and ddC will benefit in the treatment of these patients.

Condition or disease	Intervention/treatment	Phase
HIV Infections	Drug: Zidovudine; Drug: Zalcitabine	Phase 3

Detailed Description:

While treatment with AZT has been found to be effective in prolonging survival and reducing the numbers of opportunistic infections in patients with AIDS, during the second year of administration of AZT an acceleration in mortality has been observed. The reasons for this are not known at this time. The study of what may be an AZT-resistant strain of HIV may benefit patients who have been and are still receiving AZT or another drug used in treating HIV ddC. It is hoped that the comparison of the effectiveness of AZT and ddC will benefit in the treatment of these patients.

Following tests to evaluate their health, patients are chosen at random to receive either AZT or ddC. AZT is given by mouth at the patients' current dose. ddC is given by mouth every 8 hours. Treatment continues for up to 12 months. Patients are required to visit the clinic every 2 weeks up to week 12 and then once a month. Blood samples are taken to monitor the safety and effectiveness of treatment.

Study Design

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Study Type :	Interventional (Clinical Trial)
Enrollment :	120 participants
Allocation:	Randomized
Primary Purpose:	Treatment
Official Title:	A Randomized, Unblinded Trial of Zidovudine Versus ddC in the Treatment of Patients Status Post PCP Who Received Long-Term Zidovudine Therapy in Protocol ACTG 002
Actual Study Completion Date :	September 1992

Arms and Interventions

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Outcome Measures

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Eligibility Criteria

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Ages Eligible for Study:	12 Years and older (Child, Adult, Senior)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria

Required:

• Prior zidovudine (AZT) therapy for 9 months.

Concurrent Medication:

Allowed:

• Chemoprophylaxis for Pneumocystis carinii pneumonia (PCP) with aerosolized pentamidine of 300 mg every 4 weeks through the Respirgard II nebulizer.
• Maintenance treatment with pyrimethamine, sulfadiazine, amphotericin, fluconazole, ketoconazole, acyclovir, or inhaled pentamidine for subjects who have recovered from toxoplasmosis, cryptococcosis, candidiasis, herpes infection, or PCP.
• Dapsone for PCP.
• Pyrimethamine-sulfadoxine for toxoplasmosis.
• Ganciclovir (DHPG) for maintenance only for cytomegalovirus (CMV) retinitis.
• Note: Any approved medications can be used to treat an opportunistic infection. All concurrent medications should be kept to a minimum and recorded.

Patients must be positive for HIV by ELISA test and must have been receiving zidovudine (AZT) therapy for at least 9 months and have received AZT within 90 days prior to entry into the study.

Patients may be transfusion dependent as long as no more than 3 units of blood are needed in a 21-day period and the hemoglobin does not fall below 6.4 g/dl on two consecutive occasions despite the transfusions.

Exclusion Criteria

Concurrent Medication:

Excluded:

• Antiretroviral study medications other than zidovudine (AZT) and biologic response modifiers.
• Corticosteroids and chronic aspirin.
• Cimetidine.
• Flurazepam.
• Indomethacin.
• Ranitidine.
• Probenecid.
• Other experimental medications.

Patients will be excluded from the study for the following reasons:

• Removal from zidovudine (AZT) during treatment on ACTG protocol 002 for recurrent grade 4 toxicity.
• Removal from prior dideoxycytidine (ddC) therapy for peripheral neuropathy = or > grade 3.
• Visceral or extensive Kaposi's sarcoma requiring therapy or another malignancy requiring therapy.
• Toxicity grades according to NIAID Recommendations for Grading Acute and Subacute Toxic Effects (Adults).

Prior Medication:

Excluded:

• Antiretroviral study medications other than zidovudine (AZT) and biologic response modifiers.
• Patients may not have visceral or extensive Kaposi's sarcoma requiring therapy or another malignancy requiring therapy.

Contacts and Locations

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Locations

United States, California
USC CRS
Los Angeles, California, United States, 90033
Ucsd, Avrc Crs
San Diego, California, United States, 92103
United States, Florida
Univ. of Miami AIDS CRS
Miami, Florida, United States, 33136
United States, Maryland
Johns Hopkins Adult AIDS CRS
Baltimore, Maryland, United States, 21287
United States, Pennsylvania
Pitt CRS
Pittsburgh, Pennsylvania, United States

Sponsors and Collaborators

National Institute of Allergy and Infectious Diseases (NIAID)

Investigators

Study Chair:	Fischl M
Study Chair:	Richman D
Study Chair:	Murray H

More Information

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Publications:

Henry K, Tierney C, Kahn J, Balfour H, Jiang Q, Kmack A, Fischl M. A randomized, double-blind, placebo-controlled study comparing combination nucleoside and triple therapy for the treatment of advanced HIV disease (CD4 less than or equal to 50/mm(3)). Conf Retroviruses Opportunistic Infect. 1997 Jan 22-26;4th:207 (abstract no LB6)

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.

Responsible Party:	National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:	NCT00000682 History of Changes
Other Study ID Numbers:	ACTG 112; 11087 ( Registry Identifier: DAIDS ES Registry Number )
First Posted:	August 31, 2001
Last Update Posted:	March 29, 2012
Last Verified:	March 2012

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

AIDS-Related Opportunistic Infections; Pneumonia, Pneumocystis carinii; Zalcitabine; Acquired Immunodeficiency Syndrome; Zidovudine

Additional relevant MeSH terms:

HIV Infections; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Immunologic Deficiency Syndromes; Immune System Diseases; Zidovudine	Zalcitabine; Antimetabolites; Molecular Mechanisms of Pharmacological Action; Reverse Transcriptase Inhibitors; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Anti-Retroviral Agents; Antiviral Agents; Anti-Infective Agents; Anti-HIV Agents