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

National Institute of Allergy and Infectious Diseases (NIAID)

Status and phase: Completed; Phase 1

Conditions: Cytomegalovirus Retinitis; HIV Infections

Treatments: Drug: Foscarnet sodium

Study type: Interventional

Funder types: NIH

Identifiers

NCT00000726

10991 (Registry Identifier)

FDA 20D

ACTG 015

Details and patient eligibility

About

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.

Full 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).

Sex: All

Ages: 13 to 65 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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.