Foscarnet Treatment of Serious CMV Retinitis Infection in Patients With Acquired Immunodeficiency Syndrome - Full Text View

Sponsored by:	National Institute of Allergy and Infectious Diseases (NIAID)
Information provided by:	National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:	NCT00000726

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 I

MedlinePlus related topics: AIDS Cytomegalovirus Infections

Drug Information available for: Foscarnet Foscarnet sodium Fosfonet sodium Phosphonoacetic acid

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Open Label, Pharmacokinetics Study
Official Title:	Foscarnet Treatment of Serious CMV Retinitis Infection in Patients With Acquired Immunodeficiency Syndrome

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

Estimated Enrollment:

53

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

Please refer to this study by its ClinicalTrials.gov identifier: NCT00000726

Locations

United States, California
San Francisco AIDS Clinic / San Francisco Gen Hosp
San Francisco, California, United States, 941102859
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
United States, New York
Mem Sloan - Kettering Cancer Ctr
New York, New York, United States, 10021

Sponsors and Collaborators

National Institute of Allergy and Infectious Diseases (NIAID)

Investigators

Study Chair:

Jacobson M

More Information

Publications:

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.

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.

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.

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. No abstract available.

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.

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)

Study ID Numbers:	ACTG 015, FDA 20D
Study First Received:	November 2, 1999
Last Updated:	June 23, 2005
ClinicalTrials.gov Identifier:	NCT00000726
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

Study placed in the following topic categories:

Opportunistic Infections
Phosphonoacetic Acid
Sexually Transmitted Diseases, Viral
Eye Diseases
Eye Infections
Acquired Immunodeficiency Syndrome
Cytomegalovirus Retinitis
Retinitis
Cytomegalovirus
Immunologic Deficiency Syndromes
Herpesviridae Infections

Cytomegalovirus retinitis
Virus Diseases
HIV Infections
AIDS-Related Opportunistic Infections
Sexually Transmitted Diseases
Cytomegalovirus Infections
DNA Virus Infections
Foscarnet
Cytomegalic inclusion disease
Retroviridae Infections
Retinal Diseases

Additional relevant MeSH terms:

Communicable Diseases
Anti-Infective Agents
RNA Virus Infections
Slow Virus Diseases
Disease
Molecular Mechanisms of Pharmacological Action
Immune System Diseases
Eye Infections, Viral
Enzyme Inhibitors
Infection

Antiviral Agents
Pharmacologic Actions
Reverse Transcriptase Inhibitors
Pathologic Processes
Anti-Retroviral Agents
Syndrome
Therapeutic Uses
Lentivirus Infections
Nucleic Acid Synthesis Inhibitors

ClinicalTrials.gov processed this record on January 15, 2009