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

History of Changes

Tracking Information

First Received Date ^ICMJE

November 2, 1999

Last Updated Date

March 28, 2012

Start Date ^ICMJE

Not Provided

Primary Completion Date

Not Provided

Current Primary Outcome Measures ^ICMJE

Not Provided

Original Primary Outcome Measures ^ICMJE

Not Provided

Change History

Complete list of historical versions of study NCT00000726 on ClinicalTrials.gov Archive Site

Current Secondary Outcome Measures ^ICMJE

Not Provided

Original Secondary Outcome Measures ^ICMJE

Not Provided

Current Other Outcome Measures ^ICMJE

Not Provided

Original Other Outcome Measures ^ICMJE

Not Provided

Descriptive Information

Brief Title ^ICMJE

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

Official Title ^ICMJE

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

Brief 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.

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).

Study Type ^ICMJE

Interventional

Study Phase

Phase 1

Study Design ^ICMJE

Endpoint Classification: Pharmacokinetics Study
Masking: Open Label
Primary Purpose: Treatment

Condition ^ICMJE

Cytomegalovirus Retinitis
HIV Infections

Intervention ^ICMJE

Drug: Foscarnet sodium

Study Arm (s)

Not Provided

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)

* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.

Recruitment Information

Recruitment Status ^ICMJE

Completed

Enrollment ^ICMJE

Completion Date

February 1992

Primary Completion Date

Not Provided

Eligibility Criteria ^ICMJE

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.

Gender

Both

Ages

13 Years to 65 Years

Accepts Healthy Volunteers

Contacts ^ICMJE

Contact information is only displayed when the study is recruiting subjects

Location Countries ^ICMJE

United States

Administrative Information

NCT Number ^ICMJE

NCT00000726

Other Study ID Numbers ^ICMJE

ACTG 015, FDA 20D, 10991

Has Data Monitoring Committee

Not Provided

Responsible Party

National Institute of Allergy and Infectious Diseases (NIAID)

Study Sponsor ^ICMJE

National Institute of Allergy and Infectious Diseases (NIAID)

Collaborators ^ICMJE

Not Provided

Investigators ^ICMJE

Study Chair:

Jacobson M

Information Provided By

National Institute of Allergy and Infectious Diseases (NIAID)

Verification Date

March 2012

^ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP

To Top