Foscarnet Treatment of Serious CMV Retinitis Infection in Patients With Acquired Immunodeficiency Syndrome

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT00000726
First received: November 2, 1999
Last updated: March 28, 2012
Last verified: March 2012
  Purpose

To explore the safety and usefulness of foscarnet, an antiviral agent, in the treatment of cytomegalovirus (CMV) retinitis. Untreated CMV retinitis is a rapidly progressive, blinding disease in AIDS patients. The manner in which foscarnet breaks down in the body and the effect of increasing periodic intravenous doses are also studied. Foscarnet is active in vitro (test tube) against herpes viruses, including CMV, by inhibiting the virus DNA polymerases, enzymes necessary for virus replication, without affecting cellular DNA polymerases. Opportunistic CMV disease in AIDS is usually seen as retinitis, colitis, esophagitis, hepatitis, pancreatitis, encephalitis, or pneumonia. Ganciclovir has been used to treat AIDS patients with CMV disease but can cause severe neutropenia (very low neutrophil cell counts). Foscarnet does not suppress the production of neutrophils or other leukocytes (myelosuppression) and has shown in vitro activity against HIV.


Condition Intervention Phase
Cytomegalovirus Retinitis
HIV Infections
Drug: Foscarnet sodium
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Pharmacokinetics Study
Masking: Open Label
Primary Purpose: Treatment
Official Title: Foscarnet Treatment of Serious CMV Retinitis Infection in Patients With Acquired Immunodeficiency Syndrome

Resource links provided by NLM:


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

Estimated Enrollment: 53
Study Completion Date: February 1992
Detailed Description:

Foscarnet is active in vitro (test tube) against herpes viruses, including CMV, by inhibiting the virus DNA polymerases, enzymes necessary for virus replication, without affecting cellular DNA polymerases. Opportunistic CMV disease in AIDS is usually seen as retinitis, colitis, esophagitis, hepatitis, pancreatitis, encephalitis, or pneumonia. Ganciclovir has been used to treat AIDS patients with CMV disease but can cause severe neutropenia (very low neutrophil cell counts). Foscarnet does not suppress the production of neutrophils or other leukocytes (myelosuppression) and has shown in vitro activity against HIV.

Treatment is given for a total of 10 weeks with a 2-week induction regimen followed by randomization to daily maintenance foscarnet for 8 weeks. If induction therapy is tolerated without unexpected toxicity, patients are allowed to self-administer foscarnet at home via central venous catheter and may receive up to 11 days of induction therapy by self-administration on an outpatient basis. Foscarnet will be administered in open-label fashion so that both investigator and patient will know the dose. Within the study, there are 8 patients who upon entering the 2nd week of maintenance foscarnet therapy are treated with zidovudine (AZT).

  Eligibility

Ages Eligible for Study:   13 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Exclusion Criteria

Concurrent Medication:

Excluded:

  • Acyclovir.
  • Zidovudine (AZT).
  • Any potentially nephrotoxic agent, especially aminoglycosides, pentamidine, or amphotericin B.

Prior Medication:

Excluded:

  • Ganciclovir.
  • Foscarnet.
  • Excluded within 7 days of study entry:
  • Any potentially nephrotoxic agent.
  • Excluded within 14 days of study entry:
  • Cytomegalovirus hyperimmune globulin in therapeutic doses.
  • Immunomodulators.
  • Biologic response modifiers.
  • Investigational agents.
  • Amphotericin B maintenance for a systemic mycosis.

Known allergy to foscarnet.

Active AIDS-defining opportunistic infection other than cytomegalovirus (CMV) including systemic mycosis, pulmonary or neurologic impairment (comatose).

Patient must be diagnosed as having:

  • AIDS CDC Group IV.C.
  • Cytomegalovirus (CMV) retinitis as identified by its characteristic ophthalmoscopic appearance and verified by fundus photography.
  • One pending culture for CMV from blood and urine prior to study entry.
  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: NCT00000726

Locations
United States, California
UCLA CARE Ctr
Los Angeles, California, United States, 90095
Los Angeles County - USC Med Ctr
Los Angeles, California, United States, 90033
USC School of Medicine / Norris Cancer Hosp
Los Angeles, California, United States, 90033
San Francisco AIDS Clinic / San Francisco Gen Hosp
San Francisco, California, United States, 941102859
United States, New York
Mem Sloan - Kettering Cancer Ctr
New York, New York, United States, 10021
Sponsors and Collaborators
Investigators
Study Chair: Jacobson M
  More Information

Publications:
Jacobson MA, Causey D, Polsky B, Hardy D, Feinberg JE, O'Donnell JJ, Kuppermann BD, Heinemann MH, Holland G, Mills J. Dose-ranging study of daily intravenous (IV) maintenance foscarnet (PFA) therapy (Rx) for cytomegalovirus (CMV) retinitis in AIDS patients (ACTG protocol 015/915). Int Conf AIDS. 1990 Jun 20-23;6(2):113 (abstract no FB96)
Jacobson MA, Causey D, Hardy D, Polsky B, Mills J, Feinberg JE. Tolerance and efficacy of daily intravenous (IV) maintenance foscarnet (PFA) therapy for cytomegalovirus (CMV) retinitis in AIDS patients (ACTG protocol 015). Int Conf AIDS. 1989 Jun 4-9;5:242 (abstract no MBP123)

Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT00000726     History of Changes
Other Study ID Numbers: ACTG 015, FDA 20D, 10991
Study First Received: November 2, 1999
Last Updated: March 28, 2012
Health Authority: United States: Federal Government

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
Retinitis
AIDS-Related Opportunistic Infections
Foscarnet
Cytomegalovirus Infections
Acquired Immunodeficiency Syndrome
Antiviral Agents

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

ClinicalTrials.gov processed this record on August 19, 2014