Clinical trial NCT00000682: 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
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: HIV Infections
Keywords: AIDS-Related Opportunistic Infections
Pneumonia, Pneumocystis carinii
Zalcitabine
Acquired Immunodeficiency Syndrome
Zidovudine
Lead sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor class: NIH
First posted: 2001-08-31
Enrollment: 120
Sex: ALL
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Primary purpose: TREATMENT

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.

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.

Eligibility 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.

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: USC CRS
state: California
city: San Diego
country: United States
facility: Ucsd, Avrc Crs
state: California
city: Miami
country: United States
facility: Univ. of Miami AIDS CRS
state: Florida
city: Baltimore
country: United States
facility: Johns Hopkins Adult AIDS CRS
state: Maryland
city: Pittsburgh
country: United States
facility: Pitt CRS
state: Pennsylvania
Study officials:
name: Fischl M
role: STUDY_CHAIR
name: Richman D
role: STUDY_CHAIR
name: Murray H
role: STUDY_CHAIR
References:
citation: 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)
citation: 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.