HIV Infections, Acquired Immunodeficiency Syndrome, Cytomegalovirus Retinitis
Conditions
Brief summary
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
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.
Interventions
DRUGGanciclovir
intravenous ganciclovir induction at 5 mg/kg twice daily for 2 weeks followed by maintenance at 10 mg/kg/day
DRUGFoscarnet
intravenous foscarnet induction at 90 mg/kg twice daily for 2 weeks, followed by maintenance therapy at 120 mg/kg/day
Sponsors
National Eye Institute (NEI)
National Institute of Allergy and Infectious Diseases (NIAID)
Johns Hopkins University
University of Wisconsin, Madison
Baylor College of Medicine
Tulane University School of Medicine
Icahn School of Medicine at Mount Sinai
New York Presbyterian Hospital
New York University
Northwestern University
University of California, Los Angeles
University of California, San Francisco
University of California, San Diego
University of Miami
University of North Carolina, Chapel Hill
Memorial Sloan Kettering Cancer Center
Johns Hopkins Bloomberg School of Public Health
Study design
Allocation
RANDOMIZED
Intervention model
FACTORIAL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Morbidity | Patients will be seen at baseline, monthly for six months, and then every three months until death or termination of the trial | To determine the best therapeutic regimen, using currently approved drugs, for treatment of relapsed cytomegalovirus (CMV) retinitis. |
Participant flow
Recruitment details
December 1992
Participants by arm
| Arm | Count |
|---|---|
| Intravenous Foscarnet intravenous foscarnet reinduction at 90 mg/kg twice daily for 2 weeks, followed by maintenance therapy at 120 mg/kg/day
Foscarnet: intravenous foscarnet induction at 90 mg/kg twice daily for 2 weeks, followed by maintenance therapy at 120 mg/kg/day | 89 |
| Intravenous Ganciclovir intravenous ganciclovir reinduction at 5 mg/kg twice daily for 2 weeks followed by maintenance at 10 mg/kg/day
Ganciclovir: intravenous ganciclovir induction at 5 mg/kg twice daily for 2 weeks followed by maintenance at 10 mg/kg/day | 94 |
| Combination Therapy 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.
Ganciclovir: intravenous ganciclovir induction at 5 mg/kg twice daily for 2 weeks followed by maintenance at 10 mg/kg/day
Foscarnet: intravenous foscarnet induction at 90 mg/kg twice daily for 2 weeks, followed by maintenance therapy at 120 mg/kg/day | 96 |
| Total | 279 |
Baseline characteristics
| Characteristic | Intravenous Foscarnet | Intravenous Ganciclovir | Combination Therapy | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 89 Participants | 94 Participants | 96 Participants | 279 Participants |
| Region of Enrollment United States | 89 participants | 94 participants | 96 participants | 279 participants |
| Sex: Female, Male Female | 7 Participants | 6 Participants | 10 Participants | 23 Participants |
| Sex: Female, Male Male | 82 Participants | 88 Participants | 86 Participants | 256 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 7 / 88 | 7 / 93 | 10 / 93 |
| serious Total, serious adverse events | 32 / 88 | 41 / 93 | 51 / 93 |
Outcome results
Primary
Morbidity
To determine the best therapeutic regimen, using currently approved drugs, for treatment of relapsed cytomegalovirus (CMV) retinitis.
Time frame: Patients will be seen at baseline, monthly for six months, and then every three months until death or termination of the trial
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Intravenous Foscarnet | Morbidity | 88 participants |
| Intravenous Ganciclovir | Morbidity | 93 participants |
| Combination Therapy | Morbidity | 93 participants |