A Study of AZT Plus Ganciclovir in Patients With AIDS and Cytomegalovirus (CMV) Infection

Phase I Studies of the Combination of AZT and DHPG (Ganciclovir) in Patients With AIDS and Cytomegalovirus Infection

To evaluate the clinical and laboratory toxicity of ganciclovir (GCV) and zidovudine (AZT) when given in combination.

Because recent information has shown AZT to be useful in treating AIDS, it is assumed that most patients with AIDS, and probably with AIDS related complex (ARC), will be receiving AZT. Because AZT is reported not to be active against cytomegalovirus (CMV), it is important to see if it is useful to give GCV along with AZT.

Study Overview

• Status: Completed
• Conditions: HIV Infections; Cytomegalovirus Infections
• Intervention / Treatment: Drug: Zidovudine; Drug: Ganciclovir

Detailed Description

Because recent information has shown AZT to be useful in treating AIDS, it is assumed that most patients with AIDS, and probably with AIDS related complex (ARC), will be receiving AZT. Because AZT is reported not to be active against cytomegalovirus (CMV), it is important to see if it is useful to give GCV along with AZT.

Patients are placed into one of four groups at entry into study according to their previous treatment:

I: Prior treatment with AZT up to the time of developing CMV infection and not requiring dose reduction of AZT for toxicity.

II: Prior treatment with AZT up to the time of developing CMV infection and requiring dose reduction of AZT for toxicity.

III: Prior therapy with GCV for CMV infection. These patients should already be in the maintenance phase, having completed a minimum of 2 weeks of induction therapy.

IV: No prior therapy with either AZT or GCV.

Treatment lasts 24 weeks and consists of two treatment plans:

A: Patients not previously treated with GCV are started on GCV for an additional 22 weeks. GCV is given as a 1-hour infusion. All patients are started on AZT at the lowest dose. B: For patients with chronic CMV disease who are receiving GCV maintenance, GCV is administered as a 1-hour infusion 5 days/week.

AZT is added and treatment with GCV is standardized prior to beginning of the study.

• Study Type: Interventional
• Enrollment: 60
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • California
    • San Diego, California, United States, 921036325
      • Univ of California / San Diego Treatment Ctr
  • New York
    • New York, New York, United States, 10016
      • Bellevue Hosp / New York Univ Med Ctr
    • Rochester, New York, United States, 14642
      • Univ of Rochester Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria

Concurrent Medication:

Allowed:

• Symptomatic therapy such as analgesics, antihistamines, antiemetics, and antidiarrheal agents, or other supportive therapy may be administered as deemed necessary by the responsible investigator. For fever, the following regimens should be used:
• If fever above 39.0 degrees C, antipyretic therapy will be administered employing aspirin, 650 mg orally every 4 hours x 3 doses, or until fever falls below 39.0 degrees C.
• If fever of higher than 39.0 degrees C occurs for 2 consecutive days, the patient may be premedicated with aspirin.

Exclusion Criteria

• Active alcohol or drug abuse.

Co-existing Condition:

Excluded:

• Patients with other life-threatening and uncontrolled opportunistic infections on enrollment.

Patients with the following prior conditions are excluded if they:

• Have other life-threatening and uncontrolled opportunistic infections on enrollment.

Prior Medication:

Excluded within 1 week of study entry:

• Systemic therapy with antimetabolite.
• Cytotoxic drug.
• Interferon.
• Immunologic modulators.
• Corticosteroids.
• Nucleoside analogs other than zidovudine (AZT).
• Excluded within 2 weeks of study entry:
• Therapy for any other opportunistic infections.
• Excluded within 2 months of study entry:
• Ribavirin.

Prior Treatment:

Excluded within 2 weeks of study entry (for treatment group I):

• Blood transfusion.
• Excluded within 1 month of study entry (for treatment groups II and III):
• Blood transfusion.

All patients must be:

• Able to provide informed consent.
• Likely to be available for follow-up for at least 4 months.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Masking: None (Open Label)

Collaborators and Investigators

• Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
• Investigators: Study Chair: Richman D; Study Chair: Reichman RC; Study Chair: Hochster H

Publications and helpful links

General Publications

• Hochster H, Dieterich D, Bozzette S, Reichman RC, Connor JD, Liebes L, Sonke RL, Spector SA, Valentine F, Pettinelli C, et al. Toxicity of combined ganciclovir and zidovudine for cytomegalovirus disease associated with AIDS. An AIDS Clinical Trials Group Study. Ann Intern Med. 1990 Jul 15;113(2):111-7. doi: 10.7326/0003-4819-113-2-111.

Study record dates

Study Major Dates

• Study Completion (Actual): February 1, 1990

Study Registration Dates

• First Submitted: November 2, 1999
• First Submitted That Met QC Criteria: August 30, 2001
• First Posted (Estimate): August 31, 2001

Study Record Updates

• Last Update Posted (Actual): November 4, 2021
• Last Update Submitted That Met QC Criteria: October 28, 2021
• Last Verified: October 1, 2021

More Information

Terms related to this study

• Keywords: Drug Therapy, Combination; Acquired Immunodeficiency Syndrome; AIDS-Related Opportunistic Infections; Drug Evaluation; Zidovudine; Cytomegalovirus Infections; Ganciclovir
• Additional Relevant MeSH Terms: Pathologic Processes; Virus Diseases; Disease Attributes; DNA Virus Infections; Herpesviridae Infections; Infections; Communicable Diseases; Cytomegalovirus Infections; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Reverse Transcriptase Inhibitors; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Antimetabolites; Zidovudine; Ganciclovir; Ganciclovir triphosphate
• Other Study ID Numbers: ACTG 004; 10980 (Other Identifier: Fred Hutch/University of Washington Cancer Consortium)