Clinical trial NCT00000726: Foscarnet Treatment of Serious CMV Retinitis Infection in Patients With Acquired Immunodeficiency Syndrome
Official title: Foscarnet Treatment of Serious CMV Retinitis Infection in Patients With Acquired Immunodeficiency Syndrome
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Cytomegalovirus Retinitis
HIV Infections
Keywords: Retinitis
AIDS-Related Opportunistic Infections
Foscarnet
Cytomegalovirus Infections
Acquired Immunodeficiency Syndrome
Antiviral Agents
Lead sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor class: NIH
First posted: 2001-08-31
Enrollment: 53
Sex: ALL
Minimum age (years): 13
Maximum age (years): 65
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Primary purpose: TREATMENT

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).

Eligibility 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.

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Los Angeles County - USC Med Ctr
state: California
city: Los Angeles
country: United States
facility: USC School of Medicine / Norris Cancer Hosp
state: California
city: Los Angeles
country: United States
facility: UCLA CARE Ctr
state: California
city: San Francisco
country: United States
facility: San Francisco AIDS Clinic / San Francisco Gen Hosp
state: California
city: New York
country: United States
facility: Mem Sloan - Kettering Cancer Ctr
state: New York
Study officials:
name: Jacobson M
role: STUDY_CHAIR
References:
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. doi: 10.1128/AAC.38.5.1190.
citation: 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. doi: 10.1128/AAC.33.5.742.
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. doi: 10.1128/AAC.33.5.736.
citation: 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.
citation: 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. doi: 10.1093/infdis/168.2.444.
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)
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)