Studies of the Ocular Complications of AIDS (SOCA)--Cytomegalovirus Retinitis Retreatment Trial (CRRT)

Study Overview
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Brief Summary
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To compare the relative merits of three therapeutic regimens in patients with AIDS and CMV retinitis who have been previously treated but whose retinitis either is nonresponsive or has relapsed. These three therapeutic regimens were (1) foscarnet, (2) high-dose ganciclovir, and (3) combination foscarnet and ganciclovir. To compare two treatment strategies in patients with relapsed or nonresponsive CMV retinitis: (1) continuing the same anti-CMV drug or (2) switching to the alternate drug.

Detailed Description
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CMV retinitis is the most common intraocular infection in patients with AIDS and is estimated to affect 35 to 40 percent of patients with AIDS. Untreated CMV retinitis is a progressive disorder, the end result of which is total retinal destruction and blindness. At the time of this trial, drugs approved by the United States Food and Drug Administration (FDA) for the treatment of CMV retinitis were ganciclovir (Cytovene) and foscarnet (Foscavir). Although most retinitis responds well to initial therapy with systemically administered drugs, given enough time, nearly all patients will suffer a relapse of the retinitis. Relapsed retinitis generally responds to reinduction and maintenance therapy, but the interval between successive relapses progressively shortens. The CRRT addressed the issue of the management of relapsed CMV retinitis. The CRRT was a multicenter, randomized, controlled clinical trial comparing three regimens in patients with relapsed retinitis. Patients with AIDS and CMV retinitis that had relapsed or was nonresponsive to initial therapy were randomized to one of three regimens: (1) intravenous foscarnet reinduction at 90 mg/kg twice daily for 2 weeks, followed by maintenance therapy at 120 mg/kg/day; (2) intravenous ganciclovir reinduction at 5 mg/kg twice daily for 2 weeks followed by maintenance at 10 mg/kg/day; and (3) combination therapy, wherein patients continued their previous therapy and were reinduced with the second drug and then placed on maintenance therapy with foscarnet at 90 mg/kg/day and ganciclovir at 5 mg/kg/day.

Official Title
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Cytomegalovirus Retinitis Retreatment Trial

Conditions
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HIV Infections, Acquired Immunodeficiency Syndrome, Cytomegalovirus Retinitis

Intervention / Treatment
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* Drug: Ganciclovir
* Drug: Foscarnet


Participation Criteria
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Eligibility Criteria
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inclusion criteria: Males and females eligible for the CRRT must have been age 18 years or older and have had AIDS and CMV retinitis. They must have had active CMV despite a minimum of 28 days of previous treatment with an anti-CMV drug. Furthermore, they must have had an absolute neutrophil count greater than or equal to 500 cells/µL, platelet count greater than or equal to 20,000 cells/µL, and a serum creatinine < 2.5 mg/dL in order to tolerate the drug regimens. exclusion criteria: history of intolerance to ganciclovir or foscarnet, history of therapy involving the combination of foscarnet and ganciclovir, unwillingness to practice appropriate birth control, active drug or alcohol abuse, media opacity, retinal detachment not scheduled for surgical repair

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: intravenous foscarnet<br>intravenous foscarnet reinduction at 90 mg/kg twice daily for 2 weeks, followed by maintenance therapy at 120 mg/kg/day | Drug: Foscarnet<br>* intravenous foscarnet induction at 90 mg/kg twice daily for 2 weeks, followed by maintenance therapy at 120 mg/kg/day<br>* Other names: foscavir;|
| Active Comparator: intravenous ganciclovir<br>intravenous ganciclovir reinduction at 5 mg/kg twice daily for 2 weeks followed by maintenance at 10 mg/kg/day | Drug: Ganciclovir<br>* intravenous ganciclovir induction at 5 mg/kg twice daily for 2 weeks followed by maintenance at 10 mg/kg/day<br>* Other names: cytovene;|
| Active Comparator: combination therapy<br>combination therapy, wherein patients continued their previous therapy and were reinduced with the second drug and then placed on maintenance therapy with foscarnet at 90 mg/kg/day and ganciclovir at 5 mg/kg/day. | Drug: Ganciclovir<br>* intravenous ganciclovir induction at 5 mg/kg twice daily for 2 weeks followed by maintenance at 10 mg/kg/day<br>* Other names: cytovene;Drug: Foscarnet<br>* intravenous foscarnet induction at 90 mg/kg twice daily for 2 weeks, followed by maintenance therapy at 120 mg/kg/day<br>* Other names: foscavir;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Morbidity | To determine the best therapeutic regimen, using currently approved drugs, for treatment of relapsed cytomegalovirus (CMV) retinitis. | Patients will be seen at baseline, monthly for six months, and then every three months until death or termination of the trial |