Clinical trial NCT00002437: The Safety and Effectiveness of Cidofovir in the Treatment of Cytomegalovirus (CMV) of the Eyes in Patients With AIDS
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Cytomegalovirus Retinitis
HIV Infections
Keywords: Retinitis
Probenecid
Drug Therapy, Combination
Cytomegalovirus Infections
Acquired Immunodeficiency Syndrome
Antiviral Agents
cidofovir
Lead sponsor: NIH AIDS Clinical Trials Information Service
Sponsor class: INDUSTRY
First posted: 2001-08-31
Enrollment: 48
Sex: ALL
Minimum age (years): 13
Maximum age (years): 60
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: 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.

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Los Angeles County - USC Med Ctr
state: California
city: Orange
country: United States
facility: UCI Med Ctr
state: California
city: San Francisco
country: United States
facility: Mount Zion Med Ctr
state: California
city: Boston
country: United States
facility: Beth Israel Hosp
state: Massachusetts
city: Princeton
country: United States
facility: Besselaar Associates
state: New Jersey
city: Rochester
country: United States
facility: Univ of Rochester Med Ctr
state: New York
city: Chapel Hill
country: United States
facility: Univ of North Carolina Hosps
state: North Carolina
city: San Antonio
country: United States
facility: Audie L Murphy Veterans Administration Hosp
state: Texas
city: London SW 10
country: United Kingdom
facility: Charing Cross and Westminster Med School
Study officials:
References:
citation: 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