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

HIV Infections Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00000726
• Other study ID #: ACTG 015
• Secondary ID: FDA 20D10991
• Status: Completed
• Phase: Phase 1
• Est. completion date: February 1992

Study information

• Verified date: October 2021
• Source: National Institute of Allergy and Infectious Diseases (NIAID)
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 53
• Est. completion date: February 1992
• Accepts healthy volunteers: No
• Gender: All
• Age group: 13 Years to 65 Years

Eligibility

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.

Related Conditions & MeSH terms

• Acquired Immunodeficiency Syndrome
• Communicable Diseases
• Cytomegalovirus Retinitis
• HIV Infections
• Immunologic Deficiency Syndromes
• Infections
• Retinitis

Intervention

Drug:
• Foscarnet sodium

Locations

Country	Name	City	State
United States	Los Angeles County - USC Med Ctr	Los Angeles	California
United States	UCLA CARE Ctr	Los Angeles	California
United States	USC School of Medicine / Norris Cancer Hosp	Los Angeles	California
United States	Mem Sloan - Kettering Cancer Ctr	New York	New York
United States	San Francisco AIDS Clinic / San Francisco Gen Hosp	San Francisco	California

Sponsors (1)

Lead Sponsor	Collaborator
National Institute of Allergy and Infectious Diseases (NIAID)

Country where clinical trial is conducted

United States, 

References & Publications (7)

Aweeka F, Gambertoglio J, Mills J, Jacobson MA. Pharmacokinetics of intermittently administered intravenous foscarnet in the treatment of acquired immunodeficiency syndrome patients with serious cytomegalovirus retinitis. Antimicrob Agents Chemother. 1989 May;33(5):742-5. — View Citation

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)

Jacobson MA, Causey D, Polsky B, Hardy D, Chown M, Davis R, O'Donnell JJ, Kuppermann BD, Heinemann MH, Holland GN, et al. A dose-ranging study of daily maintenance intravenous foscarnet therapy for cytomegalovirus retinitis in AIDS. J Infect Dis. 1993 Aug;168(2):444-8. — View Citation

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, Crowe S, Levy J, Aweeka F, Gambertoglio J, McManus N, Mills J. Effect of Foscarnet therapy on infection with human immunodeficiency virus in patients with AIDS. J Infect Dis. 1988 Oct;158(4):862-5. — View Citation

Jacobson MA, O'Donnell JJ, Mills J. Foscarnet treatment of cytomegalovirus retinitis in patients with the acquired immunodeficiency syndrome. Antimicrob Agents Chemother. 1989 May;33(5):736-41. — View Citation

Jacobson MA, Polsky B, Causey D, Davis R, Tong W, O'Donnell JJ, Kuppermann BD, Heinemann MH, Feinberg J, Lizak P, et al. Pharmacodynamic relationship of pharmacokinetic parameters of maintenance doses of foscarnet and clinical outcome of cytomegalovirus retinitis. Antimicrob Agents Chemother. 1994 May;38(5):1190-3. — View Citation