To compare the newest CMV retinitis drug, cidofovir, with a regimen of the ganciclovir intraocular device plus oral ganciclovir with respect to efficacy in preventing vision loss.

To compare a treatment regimen that incorporates highly active local therapy (ganciclovir device) with a treatment regimen that does not.

Condition	Treatment or Intervention	Phase
Cytomegalovirus Retinitis HIV Infections	Device: Ganciclovir Intraocular Device  Drug: Ganciclovir  Drug: Cidofovir	Phase III

Further Study Details: 

Cytomegalovirus (CMV) is among the most frequently encountered opportunistic infections in patients with AIDS. In the era of prophylaxis for pneumocystic pneumonia, CMV disease is estimated to affect 45 percent of patients with AIDS sometime between the diagnosis of AIDS and death. Retinitis has been estimated to account for up to 85 percent of CMV disease in these patients, making CMV retinitis the most common ocular infection encountered. CMV retinitis is a relatively late-stage manifestation, associated with CD4+ T-cell counts < 100 cells/uL and often < 50 cells/uL.

All currently available treatments for CMV suppress viral replication but do not eliminate the virus from the body. Discontinuation of therapy is associated with a prompt relapse of the retinitis. Despite the use of chronic suppressive therapy, relapse of the retinitis generally occurs, at least with systemically administered anti-CMV drugs.

The first two treatments approved for CMV retinitis were intravenous ganciclovir and intravenous foscarnet. Both are given by daily intravenous infusions and therefore require central venous catheters. The development of newer treatments has focused not only on efficacious treatments, but also on treatments that do not require central venous catheters. Available treatments now include oral ganciclovir, the ganciclovir intraocular device, and intravenous cidofovir.

In vitro data suggest that combination therapies are synergistic in inhibiting viral replication; these therapies include a foscarnet-ganciclovir combination and a cidofovir-ganciclovir combination. In the SOCA--CMV Retinitis Retreatment Trial, the combination of intravenous ganciclovir and foscarnet was more effective than either drug alone for the treatment of relapsed retinitis. Therefore, the combination of intermittent intravenous cidofovir and daily oral ganciclovir may be an attractive therapy for relapsed disease because it may provide synergy for controlling both ocular and visceral disease while not necessitating either a central venous catheter or an intraocular surgical procedure.

The Ganciclovir-Cidofovir CMV Retinitis Trial (GCCRT) is a randomized, multicenter clinical trial. Patients will be assigned to receive one of two regimens: (1) ganciclovir intraocular device plus oral ganciclovir or (2) intravenous cidofovir. The intraocular device will be surgically implanted at baseline and again every 6 to 8 months in eyes with CMV retinitis. Oral ganciclovir is taken at a dose of 1 gram three times daily. Cidofovir will be administered intravenously at 5 mg/kg once weekly for 2 consecutive weeks and once every 2 weeks thereafter. If disease progression occurs in patients receiving cidofovir, patients will be given reinduction therapy, and oral ganciclovir at a dose of 1 gram three times per day will be added to the treatment. If patients assigned to cidofovir are unable to tolerate that regimen, an alternative systemic regimen will be recommended.

Study outcome variables include a decrease of three or more lines from baseline in best corrected visual acuity and rate of visual field loss. The study will also assess other variables including mortality, blood CMV and HIV load, quality of life, and medical costs. Treatment assignment will not be masked to either patients or clinicians; however, reading of fundus photographs to determine both change in retinal involvement and progression will be masked.

Ages Eligible for Study:  13 Years and above,  Genders Eligible for Study:  Both

Criteria

Males and females age 13 years and older with diagnoses of AIDS and active CMV retinitis will be eligible. Patients must have a best corrected visual acuity of greater than or equal to 20/100 in at least one eye affected by CMV retinitis with at least one lesion 750 u or greater that can be photographed.

California
      Jules Stein Eye Institute, University of California, Los Angeles, Los Angeles,  California,  90095-7003,  United States
      Shiley Eye Center Center, 0946, University of California, San Diego, La Jolla,  California,  92093-0946,  United States
      Beckman Vision Center, University of California, San Francisco, San Francisco,  California,  94143,  United States
      LAC/USC Medical Center, 5P21 Rand Schrader Clinic, Los Angeles,  California,  90033,  United States
      Department of Ophthalmology, University of California, Irvine, Irvine,  California,  92697-4375,  United States
Florida
      Bascom Palmer Eye Institute, University of Miami, Miami,  Florida,  33136,  United States
      University of South Florida, MDC Box 21, Tampa,  Florida,  33612-4799,  United States
Georgia
      The Emory Clinic, Emory University, Atlanta,  Georgia,  30322,  United States
Illinois
      Department of Ophthalmology, Northwestern University, Chicago,  Illinois,  60611,  United States
Indiana
      Division of Infectious Diseases, Indiana University, Indianapolis, Indianapolis,  Indiana,  46202-2879,  United States
Louisiana
      LSU Eye Center, Louisiana State University Medical Center, New Orleans,  Louisiana,  70112,  United States
Maryland
      The Wilmer Ophthalmological Institute, The Johns Hopkins University School of Medicine, Baltimore,  Maryland,  21287-9217,  United States
Massachusetts
      Harvard/BCH AIDS Clinical Trials Unit, Massachusetts General Hospital, Boston,  Massachusetts,  02114,  United States
New Jersey
      UMDNJ-New Jersey Medical School, Newark,  New Jersey,  07103-2499,  United States
New York
      Department of Ophthalmology, New York Hospital-Cornell Medical Center, New York,  New York,  10021,  United States
      Department of Ophthalmology, Mount Sinai School of Medicine, New York,  New York,  10029-6574,  United States
      Department of Ophthalmology, New York University Medical Center, New York,  New York,  10016,  United States
North Carolina
      University of North Carolina at Chapel Hill, Chapel Hill,  North Carolina,  27599-7030,  United States
Texas
      Cullen Eye Institute, Baylor College of Medicine, Houston,  Texas,  77030,  United States

Study ID Numbers:  NEI-42
Record last reviewed:  October 2001
Last Updated:  October 13, 2004
Record first received:  September 23, 1999
ClinicalTrials.gov Identifier:  NCT00000143
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08