The Safety and Effectiveness of Cidofovir in the Treatment of Cytomegalovirus (CMV) of the Eyes in Patients With AIDS

HIV Infections Clinical Trial

Official title:

A Phase II/III Study of the Safety and Efficacy of 1-(S)-(3-Hydroxy-2-Phosphonylmethoxypropyl)Cytosine Dihydrate (Cidofovir; HPMPC) for the Treatment of Peripheral Cytomegalovirus Retinitis in Patients With AIDS

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00002437
• Other study ID #: 216A
• Secondary ID: GS-93-106
• Status: Completed
• Phase: Phase 2
• First received: November 2, 1999
• Last updated: June 23, 2005

Study information

• Verified date: November 1994
• Source: NIH AIDS Clinical Trials Information Service
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

To determine whether cidofovir (HPMPC) therapy administered by intravenous infusion can extend the time to progression of peripheral cytomegalovirus (CMV) retinitis in AIDS patients. To evaluate the safety and tolerance of HPMPC therapy when administered by intravenous infusion in AIDS patients with CMV retinitis that is not immediately sight-threatening. To evaluate the virologic effects of intravenous HPMPC therapy on CMV shedding in urine, blood, and/or semen. To evaluate the impact of HPMPC therapy on visual acuity.

Description:

Patients are randomized to one of two treatment arms. Group A receives HPMPC by IV infusion weekly for 2 consecutive weeks (induction) and then every other week (maintenance) with oral probenecid and IV hydration. Group B receives no treatment until the time of retinitis progression (deferred treatment), at which time they receive the same regimen as Group A, provided retinitis progression is not immediately sight-threatening.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 48
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 13 Years to 60 Years

Eligibility

Inclusion Criteria

Concurrent Medication:

Allowed:

• Antiretroviral agents.

• Oral trimethoprim/sulfamethoxazole.

• Aerosolized pentamidine.

• Dapsone.

• Fluconazole.

• Rifabutin.

• Filgrastim (G-CSF).

• p24 vaccine.

Patients must have:

• Diagnosis of AIDS by CDC criteria.

• Diagnosis of peripheral (not immediately sight-threatening) CMV retinitis.

• Visual acuity in the affected eye of >= three lines on the ETDRS (Early Treatment Diabetic Retinopathy Study) chart at 1 m distance.

• Life expectancy of at least 3 months.

• Consent of parent or guardian in patients less than 18 years of age.

Prior Medication:

Allowed:

• Acyclovir.

• Prior ganciclovir, foscarnet, or CMV hyperimmune immunoglobulin if given solely as prophylaxis.

Exclusion Criteria

Co-existing Condition:

Patients with the following symptoms or conditions are excluded:

• Media opacity that precludes visualization of the fundus of both eyes.

• Retinal detachment.

• Clinically significant cardiac disease, including symptoms of ischemia, congestive heart failure, or arrhythmia.

• Active medical problems considered sufficient to hinder study compliance.

• Known clinically significant allergy to probenecid.

Concurrent Medication:

Excluded:

• Acyclovir (may be reinstituted following development of herpetic lesions).

• Ganciclovir.

• Foscarnet.

• Amphotericin B.

• Diuretics.

• Aminoglycoside antibiotics.

• CMV hyperimmune immunoglobulin.

• Intravenous pentamidine.

• Other nephrotoxic agents.

• Other investigational drugs with potential nephrotoxicity.

Prior Medication:

Excluded:

• Prior ganciclovir, foscarnet, or CMV hyperimmune immunoglobulin as therapy for CMV disease (although permitted if previously received solely as prophylaxis).

Excluded within 1 week prior to study entry:

• Amphotericin B.

• Vidarabine.

• Other nephrotoxic agents.

• Aminoglycoside antibiotics.

• Intravenous pentamidine. Drug or alcohol abuse.

Study Design

Endpoint Classification: Safety Study, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Cytomegalovirus Retinitis
• HIV Infections
• Retinitis

Intervention

Drug:
• Cidofovir

• Probenecid

Locations

Country	Name	City	State
United Kingdom	Charing Cross and Westminster Med School	London SW 10
United States	Beth Israel Hosp	Boston	Massachusetts
United States	Univ of North Carolina Hosps	Chapel Hill	North Carolina
United States	Los Angeles County - USC Med Ctr	Los Angeles	California
United States	UCI Med Ctr	Orange	California
United States	Besselaar Associates	Princeton	New Jersey
United States	Univ of Rochester Med Ctr	Rochester	New York
United States	Audie L Murphy Veterans Administration Hosp	San Antonio	Texas
United States	Mount Zion Med Ctr	San Francisco	California

Sponsors (1)

Lead Sponsor	Collaborator
Gilead Sciences

Countries where clinical trial is conducted

United States,  United Kingdom, 

References & Publications (1)

Lalezari J, et al. A phase II/III randomized study of immediate versus deferred intravenous (IV) cidofovir (CDV, HPMPC) for the treatment of peripheral CMV retinitis (CMV-R) in patients with AIDS. Natl Conf Hum Retroviruses Relat Infect (2nd). 1995 Jan 29-Feb 2:170