HIV Infections, Cytomegalovirus Retinitis
Conditions
Brief summary
To evaluate the relative safety and efficacy of ganciclovir and foscarnet as initial treatment of patients with cytomegalovirus (CMV) retinitis.
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. The first two drugs approved by the United States Food and Drug Administration (FDA) for the treatment of CMV retinitis were ganciclovir (Cytovene) and foscarnet (Foscavir). At the time of this trial, both ganciclovir and foscarnet were available only as intravenous formulations. Both drugs were given in a similar two-step fashion: an initial 2-week course of high-dose therapy (induction) to control the infection followed by long-term lower dose therapy to prevent relapse (maintenance). The FGCRT compared foscarnet and ganciclovir as initial therapy for CMV retinitis. The FGCRT was a multicenter, randomized, controlled clinical trial comparing foscarnet and ganciclovir as initial therapy for CMV retinitis. Patients with previously untreated CMV retinitis were randomized to therapy with either intravenous ganciclovir or intravenous foscarnet. The outcome measures of this trial were survival, retinitis progression, loss of visual function (visual acuity and visual field), and morbidity.
Interventions
DRUGFoscarnet
60 mg/kg every 8 hours, 90 mg/kg/day
DRUGGanciclovir
5 mg/kg every 12 hours, 5 mg/kg every 24 hours
Sponsors
National Eye Institute (NEI)
Johns Hopkins University
University of Wisconsin, Madison
Baylor College of Medicine
Louisiana State University Health Sciences Center in New Orleans
New York Presbyterian Hospital
Icahn School of Medicine at Mount Sinai
NYU Langone Health
Northwestern University
University of California, Los Angeles
University of California, San Diego
University of California, San Francisco
University of Miami
University of Massachusetts, Worcester
Memorial Sloan Kettering Cancer Center
Johns Hopkins Bloomberg School of Public Health
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
13 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* CMV retinitis in one or both eyes * At least 1/4 disk are of one CMV lesion photographable * Diagnosis of AIDS as defined by Center for Disease Control criteria or documented HIV infection * Age 13 and greater * Visual acuity ≥ 3/200 in at least one eye diagnosed with CMV retinitis * Absolute neutrophil count ≥ 1,000 cells/µl * Platelet ≥ 25,000 cells/µl * Serum creatinine ≥ 2.0 mg/dl * Karnofsky score ≥ 60 * Informed consent
Exclusion criteria
* Previous treatment of CMV retinitis * Treatment with anti-CMV therapy for an extra-ocular CMV infection currently or in the past 28 days * Known or suspected allergy to study drugs * Pregnant or Lactating
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Mortality | All patients enrolled will be followed until a common study closing date, which was chosen to provide a minimum of 1 year of follow-up for all patients enrolled in the trial. |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Foscarnet The induction dose for foscarnet is 60 mg/kg every 8 hours. Full dose maintenance therapy for foscarnet is 90 mg/kg/day
Foscarnet: 60 mg/kg every 8 hours, 90 mg/kg/day
Ganciclovir: 5 mg/kg every 12 hours, 5 mg/kg every 24 hours | 107 |
| Ganciclovir The induction dose for ganciclovir is 5 mg/kg every 12 hours. Full dose maintenance therapy for ganciclovir is 5 mg/kg every 24 hours, 7 days a week.
Foscarnet: 60 mg/kg every 8 hours, 90 mg/kg/day
Ganciclovir: 5 mg/kg every 12 hours, 5 mg/kg every 24 hours | 127 |
| Total | 234 |
Baseline characteristics
| Characteristic | Foscarnet | Ganciclovir | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 107 Participants | 127 Participants | 234 Participants |
| Region of Enrollment United States | 107 participants | 127 participants | 234 participants |
| Sex: Female, Male Female | 9 Participants | 11 Participants | 20 Participants |
| Sex: Female, Male Male | 98 Participants | 116 Participants | 214 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 107 | 0 / 127 |
| serious Total, serious adverse events | 60 / 107 | 73 / 127 |
Outcome results
Primary
Mortality
Time frame: All patients enrolled will be followed until a common study closing date, which was chosen to provide a minimum of 1 year of follow-up for all patients enrolled in the trial.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Foscarnet | Mortality | 107 participants |
| Ganciclovir | Mortality | 127 participants |