A Multicenter, Double Blind, Comparative Study of Zidovudine Alone Versus Zidovudine and Acyclovir as Treatment for HIV-Infected Patients With CD4+ Counts Less Than 200 Cells/mm3

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT00000712
First received: November 2, 1999
Last updated: March 15, 2012
Last verified: March 2012
  Purpose

Original design: The study's purpose is to compare the effects of zidovudine (AZT) alone to the combination of AZT and acyclovir (ACV) to determine if AZT/ACV is associated with a lower death rate and fewer AIDS related opportunistic infections compared to AZT alone, and to investigate the effect of these treatment plans on cytomegalovirus (CMV) and Epstein-Barr virus (EBV) infections. The study evaluates two doses of AZT used alone versus two doses of AZT combined with ACV. Per 12/11/92 amendment: Another antiretroviral agent may be substituted for AZT.

AZT has been shown to increase the life span of patients with AIDS or advanced AIDS related complex and patients being treated for Pneumocystis carinii pneumonia. Drugs that increase the effectiveness of AZT against HIV may also decrease the need for high doses of AZT. This might reduce some of the negative effects of AZT while not reducing the positive effects.


Condition Intervention Phase
HIV Infections
Drug: Zidovudine
Drug: Acyclovir
Phase 2

Study Type: Interventional
Study Design: Intervention Model: Parallel Assignment
Primary Purpose: Treatment
Official Title: A Multicenter, Double Blind, Comparative Study of Zidovudine Alone Versus Zidovudine and Acyclovir as Treatment for HIV-Infected Patients With CD4+ Counts Less Than 200 Cells/mm3

Resource links provided by NLM:


Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Estimated Enrollment: 400
Study Completion Date: November 1994
Detailed Description:

AZT has been shown to increase the life span of patients with AIDS or advanced AIDS related complex and patients being treated for Pneumocystis carinii pneumonia. Drugs that increase the effectiveness of AZT against HIV may also decrease the need for high doses of AZT. This might reduce some of the negative effects of AZT while not reducing the positive effects.

AMENDED: Patients are randomly assigned to one of two treatment regimens. They receive AZT (or other antiretroviral agent) with or without ACV. Treatment Plan 1: AZT along with placebo at the same time. Treatment Plan 2: AZT and ACV. Therapy is for 104 weeks with an optional extension of 24 weeks or until the end of the study whichever comes first. The maximum duration of therapy for any patient will be 128 weeks. Medication is dispensed on a biweekly basis for the first 4 weeks, then every other month for the remainder of the study. Original design: Patients are randomly assigned to one of four treatment plans to receive AZT alone or AZT and ACV. Medications are given every 4 hours (q4h) orally (PO) while awake (WA). A total of 5 doses/day are given. The per dose schedule for the four plans are: Treatment plan 1: AZT plus placebo (an inactive medication) substituting for ACV. Treatment plan 2: AZT and AZT placebo along with an ACV placebo. Treatment plan 3: AZT and ACV. Treatment plan 4: AZT and AZT placebo and ACV.

  Eligibility

Ages Eligible for Study:   13 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria

Concurrent Medication:

Allowed:

  • Methadone maintenance. Therapies available through expanded access or treatment IND programs unless specifically excluded.
  • Allowed within 30 days of study entry:
  • Systemic steroids only if given for treatment of Pneumocystis carinii pneumonia.
  • Recommended:
  • PCP prophylaxis.

Patient must have:

  • Recovered from first episode of histologically proven Pneumocystis carinii pneumonia (PCP) or microbiologically proven AIDS-defining opportunistic infection as defined in Centers for Disease Control HIV classification group IV.
  • C-1.
  • Study entry must be within 120 days of AIDS-defining diagnosis.
  • Written documentation of positive antibody to HIV by any federally licensed ELISA test kit. This test should be confirmed by another method, for example, Western blot, radioimmunoassay (RIA), HIV culture.
  • Patients cannot be transfusion dependent (requiring blood transfusion more than once per month). The last transfusion must be > 2 weeks before entry.
  • AMENDED 90-08-27 to include HIV positive patients with CD4+ count < 200 cells/mm3.

Prior Medication:

Allowed:

  • Zidovudine (AZT) for < 365 days prior to study entry.

Exclusion Criteria

Co-existing Condition:

Patients with the following are excluded:

  • Symptomatic visceral or progressive Kaposi's sarcoma (KS) (defined by > 10 new lesions in the 30 days prior to entry).
  • Other concurrent neoplasms other than basal cell carcinoma of skin (patients who have been in complete remission for 1 year for a malignancy may be enrolled).
  • Malabsorption as defined by persistent diarrhea > 6 stools/day for > 4 weeks. Patients whose sole AIDS-defining condition is constitutional disease as defined in CDC's HIV group IV-A or neurologic disease as defined in CDC's HIV group IV-B or AIDS-associated malignancies as defined in CDC's HIV group IV-C.

Concurrent Medication:

Excluded:

  • Acyclovir (ACV) prophylaxis or frequent (> once per month) repeated courses of ACV therapy for herpes simplex virus infection.
  • Any concomitant medicine unless required.
  • Systemic therapy/prophylaxis/maintenance for AIDS-defining opportunistic infection other than prophylaxis for Pneumocystis carinii pneumonia (PCP).
  • Acetaminophen for > 72 hours. Cimetidine.
  • Flurazepam.
  • Indomethacin.
  • Ranitidine.
  • Probenecid (if receiving AZT).
  • Rifampin.
  • Rifampin-related drugs.

Patients with the following are excluded:

  • Active opportunistic infections.
  • Symptomatic visceral or progressive Kaposi's sarcoma (KS) (defined by > 10 new lesions in the 30 days prior to entry).
  • Other concurrent neoplasms other than basal cell carcinoma of skin (patients who have been in complete remission for 1 year for a malignancy may be enrolled).
  • Malabsorption as defined by persistent diarrhea > 6 stools/day for > 4 weeks.
  • Patients whose sole AIDS-defining condition is constitutional disease as defined in CDC's HIV group IV-A or neurologic disease as defined in CDC's HIV group IV-B or AIDS-associated malignancies as defined in CDC's HIV group IV-C.

Prior Medication:

Excluded:

  • Zidovudine (AZT) for > 365 days prior to study entry.
  • Excluded within 14 days of study entry:
  • Systemic acyclovir (ACV) therapy.
  • Excluded within 30 days of study entry:
  • Antiretroviral therapy (other than AZT per above).
  • Immunomodulating agents.
  • Biologic response modifiers.

Excluded within 60 days of study entry:

  • Ribavirin.

Prior Treatment:

Excluded within 30 days of study entry:

  • Cytotoxic chemotherapy or radiation therapy for Kaposi's sarcoma.

Active substance abuse that would impair compliance with study procedure.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00000712

Locations
United States, Massachusetts
Beth Israel Deaconess Med. Ctr., ACTG CRS
Boston, Massachusetts, United States, 02215
Beth Israel Deaconess - East Campus A0102 CRS
Boston, Massachusetts, United States, 02215
Bmc Actg Crs
Boston, Massachusetts, United States, 02118
Massachusetts General Hospital ACTG CRS
Worcester, Massachusetts, United States, 01655
United States, Minnesota
University of Minnesota, ACTU
Minneapolis, Minnesota, United States, 55455
United States, North Carolina
Unc Aids Crs
Chapel Hill, North Carolina, United States, 27599
Regional Center for Infectious Disease, Wendover Medical Center CRS
Greensboro, North Carolina, United States, 27401
United States, Washington
University of Washington AIDS CRS
Seattle, Washington, United States, 98122
Sponsors and Collaborators
Investigators
Study Chair: Collier AC
Study Chair: Hirsch M
Study Chair: Corey L
  More Information

Additional Information:
Publications:
Collier AC, Schoenfeld DA, Bourland D, Hirsch M, Davis LG, Corey L. Prospective comparative study of acyclovir (ACV) and zidovudine (ZDV) versus ZDV alone in patients with AIDS. Natl Conf Hum Retroviruses Relat Infect (2nd). 1995 Jan 29-Feb 2;125

Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT00000712     History of Changes
Other Study ID Numbers: ACTG 063, 11037
Study First Received: November 2, 1999
Last Updated: March 15, 2012
Health Authority: United States: Federal Government

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
AIDS-Related Opportunistic Infections
Herpesviridae Infections
Drug Evaluation
Drug Therapy, Combination
Herpesvirus 4, Human
Cytomegalovirus Infections
Acyclovir
Acquired Immunodeficiency Syndrome
Antiviral Agents
Zidovudine

Additional relevant MeSH terms:
HIV Infections
Acquired Immunodeficiency Syndrome
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Slow Virus Diseases
Acyclovir
Zidovudine
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Anti-Retroviral Agents
Anti-HIV Agents

ClinicalTrials.gov processed this record on August 27, 2014