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Suppression of Cytomegalovirus Retinitis Utilizing High Dose Intravenous Acyclovir and Oral Zidovudine in Patients With AIDS
This study has been completed.
First Received: November 2, 1999   Last Updated: August 25, 2008   History of Changes
Sponsored by: National Institute of Allergy and Infectious Diseases (NIAID)
Information provided by: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT00000693
  Purpose

To study the use of acyclovir (ACV) and zidovudine (AZT) in the treatment of cytomegalovirus (CMV) retinitis in patients with AIDS who would otherwise be treated with ganciclovir (DHPG) alone. CMV retinitis is one of the most common opportunistic infections in patients with AIDS. DHPG is at present the only drug available for widespread compassionate use in the United States. Although most patients respond to treatment with DHPG, the medication does not cure the infection. Most patients will have a relapse and will require retreatment with DHPG. Because of the large relapse rate, most people treated for CMV retinitis are placed on continuous treatment with DHPG. There are two major problems associated with ongoing use of DHPG: 1) The development of a low white blood cell (WBC) count (leukopenia) which is a known side effect of the drug; and 2) the increased risk for leukopenia when DHPG is given together with AZT, the only antiviral drug currently available for the treatment of HIV infection. Therefore, patients cannot take both AZT and DHPG at the same time because the bone marrow toxicity is made much more severe when the drugs are given together. This has resulted in the difficult decision as to whether to forgo potential life-extending therapy with AZT in order to preserve sight. An effective treatment for CMV retinitis is needed that will allow the patient to also take AZT. ACV is presently the drug of choice for severe herpes virus infections. It has been shown to be effective in suppressing severe CMV disease in patients who have received bone marrow transplants.


Condition Intervention
Cytomegalovirus Retinitis
HIV Infections
Drug: Zidovudine
Drug: Acyclovir

Study Type: Interventional
Study Design: Treatment, Open Label
Official Title: Suppression of Cytomegalovirus Retinitis Utilizing High Dose Intravenous Acyclovir and Oral Zidovudine in Patients With AIDS

Resource links provided by NLM:


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

Estimated Enrollment: 25
Detailed Description:

CMV retinitis is one of the most common opportunistic infections in patients with AIDS. DHPG is at present the only drug available for widespread compassionate use in the United States. Although most patients respond to treatment with DHPG, the medication does not cure the infection. Most patients will have a relapse and will require retreatment with DHPG. Because of the large relapse rate, most people treated for CMV retinitis are placed on continuous treatment with DHPG. There are two major problems associated with ongoing use of DHPG: 1) The development of a low white blood cell (WBC) count (leukopenia) which is a known side effect of the drug; and 2) the increased risk for leukopenia when DHPG is given together with AZT, the only antiviral drug currently available for the treatment of HIV infection. Therefore, patients cannot take both AZT and DHPG at the same time because the bone marrow toxicity is made much more severe when the drugs are given together. This has resulted in the difficult decision as to whether to forgo potential life-extending therapy with AZT in order to preserve sight. An effective treatment for CMV retinitis is needed that will allow the patient to also take AZT. ACV is presently the drug of choice for severe herpes virus infections. It has been shown to be effective in suppressing severe CMV disease in patients who have received bone marrow transplants.

Patients receive ACV intravenously and AZT orally for 12 weeks. Tolerance of the combined administration of ACV and AZT is monitored. AMENDED: AZT dose lowered and inclusion of concurrent medication expanded.

  Eligibility

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

Inclusion Criteria

Prior Medication:

Required:

  • Patients must have successfully completed remission induction therapy with ganciclovir (minimum of 14 days of therapy) for acute cytomegalovirus (CMV) retinitis within the preceding 48 hours. Patients who show no evidence of progressive disease are considered to have met criteria for successful induction.

Amended to allow:

  • Investigational triazoles.
  • Human recombinant erythropoietin (Eprex).
  • Other investigational non-antiviral therapies offered through treatment IND.

Patients must:

  • Have HIV infection as determined by a commercially licensed ELISA test confirmed by a licensed Western blot
  • Have salvageable vision (corrected acuity of 20/100 or better) in at least one eye.
  • Be capable of signing an informed consent.

Exclusion Criteria

Co-existing Condition:

Patients with the following are excluded:

  • Known or suspected allergy to one of the study medications.
  • Inability to maintain adequate hydration status.

Concurrent Medication:

Excluded:

  • Concurrent therapy with nephrotoxic agents.
  • Systemic therapy for another opportunistic infection.
  • Systemic prophylaxis for Pneumocystis carinii pneumonia (PCP).
  • Probenecid.
  • Patients are advised that validity of this trial may be jeopardized by use of other potentially antiviral or immunomodulating treatments.

Patients with the following are excluded:

  • Known or suspected allergy to one of the study medications.
  • Inability to maintain adequate hydration status.

Prior Medication:

Excluded within 2 weeks of study entry:

  • Steroids.
  • Cytotoxic or immunosuppressive drugs.
  • Investigational agents. (Amended to now allow these.) Immunomodulatory drugs (except ganciclovir).

Prior Treatment:

Excluded within 2 weeks of study entry:

  • Radiotherapy.

Risk Behavior:

Excluded:

  • History of unreliable drug intake and inability to cooperate in the testing procedures. Unwilling or unable to give informed consent or unwilling to sign approved consent form.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00000693

Locations
United States, Illinois
Rush Presbyterian - Saint Luke's Med Ctr
Chicago, Illinois, United States, 60612
Northwestern Univ Med School
Chicago, Illinois, United States, 60611
Sponsors and Collaborators
Investigators
Study Chair: HA Kessler
Study Chair: CA Benson
  More Information

Additional Information:
Publications:
Study ID Numbers: ACTG 070
Study First Received: November 2, 1999
Last Updated: August 25, 2008
ClinicalTrials.gov Identifier: NCT00000693     History of Changes
Health Authority: United States: Federal Government

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
Retinitis
Drug Evaluation
Drug Therapy, Combination
Cytomegalovirus Infections
Acyclovir
Acquired Immunodeficiency Syndrome
Zidovudine

Study placed in the following topic categories:
Antimetabolites
Sexually Transmitted Diseases, Viral
Anti-HIV Agents
Eye Diseases
Eye Infections
Acquired Immunodeficiency Syndrome
Cytomegalovirus Retinitis
Retinitis
Zidovudine
Antiviral Agents
Cytomegalovirus
Immunologic Deficiency Syndromes
Reverse Transcriptase Inhibitors
Herpesviridae Infections
Virus Diseases
Acyclovir
Anti-Retroviral Agents
HIV Infections
Sexually Transmitted Diseases
Cytomegalic Inclusion Disease
Cytomegalovirus Infections
DNA Virus Infections
Retroviridae Infections
Retinal Diseases

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

ClinicalTrials.gov processed this record on July 02, 2009