CMV Cytomegalovirus Retinitis, HIV Infections
Conditions
Brief summary
To test and evaluate the efficacy and safety of intravenous cidofovir (Vistide, previously known as HPMPC) for the treatment of retinitis.
Detailed description
CMV (cytomegalovirus) retinitis is the most common intraocular infection in patients with AIDS and is estimated to affect 35 percent to 40 percent of patients with AIDS. Untreated CMV (cytomegalovirus) retinitis is a progressive disorder, the end result of which is total retinal destruction and blindness. As of September 1997, drugs approved by the United States Food and Drug Administration (FDA) for the treatment of CMV (cytomegalovirus)retinitis were ganciclovir (Cytovene), foscarnet (Foscavir), and cidofovir (Vistide). Cidofovir has a prolonged duration of effect permitting intermittent administration. All systemically administered anti-CMV drugs are given in a similar fashion consisting of initial 2-week high-dose treatment (induction) to control the infection followed by long-term lower dose treatment (maintenance) to prevent relapse. Cidofovir is administered as an intravenous infusion once weekly for induction therapy and once every 2 weeks as maintenance therapy. The HPCRT evaluated the efficacy and safety of cidofovir therapy. The HPCRT was a multicenter, randomized, controlled clinical trial of cidofovir for the treatment of CMV (cytomegalovirus) retinitis. Patients with small peripheral CMV (cytomegalovirus) retinitis lesions (i.e., not at risk of immediate loss of visual acuity) were randomized to immediate treatment with cidofovir or deferred therapy until the retinitis had progressed. Patients randomized to immediate therapy received either 1) low-dose cidofovir at 5 mg/kg once weekly induction for 2 weeks, followed by 3 mg/kg once every 2 weeks for maintenance or 2) high-dose cidofovir at 5 mg/kg once weekly induction for 2 weeks followed by 5 mg/kg once every 2 weeks for maintenance. Patients whose retinitis progressed were given treatment according to best medical judgement, and those assigned to deferral were generally treated with cidofovir. Outcomes in this trial included retinitis progression, loss of retinal area, and morbidity.
Interventions
DRUGCidofovir
Three groups: 1. the deferral group, treatment deferred until retinitis progressed 2. Low-dose cidofovir group, 5 mg/kg of body weight once weekly for two weeks, then maintenance therapy with cidofovir, 3mg/kg once every 2 weeks. 3. High-dose cidofovir group, 5mg/kg once weekly for 2 weeks, then maintenance therapy with cidofovir, 5mg/kg once every two weeks.
Sponsors
Baylor College of Medicine
Johns Hopkins University
Louisiana State University Health Sciences Center in New Orleans
Icahn School of Medicine at Mount Sinai
New Jersey Medical School
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 North Carolina, Chapel Hill
University of South Florida
Johns Hopkins Bloomberg School of Public Health
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
13 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* diagnosis of AIDS according to the Centers for Disease Control and Prevention (CDC) * 13 years or older * Diagnosis of CMV (cytomegalovirus) retinitis as determined by a SOCA-certified Ophthalmologist. * At least one lesion whose size is one-quarter disc area or more that can be photographed. * Visual acuity in an affected eye of 3 or more lines on the (ETDRS) Early Treatment Diabetic Retinopathy Study chart at 1 meter distance (Snellen equivalent 8/200). * score of 60 or more on the Karnofsky scale. * Serum creatinine of 1.5mg/dL or less * less than 1+ proteinuria on urinalysis * Total bilirubin of 3.0 mg/dL or less * Hepatic transaminase levels that do not exceed 5 times the normal levels * Absolute neutrophil count of 750 cells/µL or greater * Platelet count of 50,000 cells/µL or greater * Hemoglobin of 7.5 g/dL or greater * Negative pregnancy test (females of childbearing potential) * All men/women of childbearing potential should practice birth control to prevent pregnancy while on study and for 3 months afterwards * Willingness/ability, with the assistance of a caregiver if necessary to comply with treatment and follow-up procedures * Signed consent statement
Exclusion criteria
* Evidence of a CMV (cytomegalovirus) retinitis lesion within zone 1. A lesion less than 1,500 µ from the margin of the optic disc or less than 3,000 µ from the center of the fovea in either eye excludes a patient. * Evidence of a CMV retinitis lesions that involves 25% or more of the retinal area regardless of location. * Previous or ongoing therapy for CMV (cytomegalovirus) disease with ganciclovir, foscarnet, CMV hyperimmune immunoglobulin, or other investigational agents solely as prophylaxis are eligible for enrollment. * Retinal detachment(s) in the affected eye(s) * media opacity that precludes visualization of the fundus of both eyes. * patients with a diagnosis of extraocular CMV (cytomegalovirus) disease. * Patients with history of clinically significant renal disease or renal dialysis. * Patients with history of clinically significant cardiac disease, including symptoms of ischemia, congestive heart failure, or arrhythmia. * pregnant or lactating * patients with active medical problems including drug or alcohol abuse which could hinder compliance with treatment or follow-up procedures. * patients receiving therapy within the previous 7 days with nephrotoxic drugs, including: Amphotericin B, Vidarabine, Aminoglycoside antibiotics, Intravenous pentamidine. Patients receiving any of these drugs must discontinue the drug(s) at least one week prior to the time of enrollment, and for the duration of the trial period. * history of clinically significant probenecid allergy.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Survival | All patients enrolled will be followed until a common study closing date |
Participant flow
Recruitment details
April 1994
Participants by arm
| Arm | Count |
|---|---|
| Treatment Deferral IV (in the vein) treatment deferred until retinitis progressed, either:
5 mg/kg IV (in the vein) of body weight once weekly for two weeks, then maintenance therapy with cidofovir, 3mg/kg once every 2 weeks, or
5mg/kg IV (in the vein) once weekly for 2 weeks, then maintenance therapy with cidofovir, 5mg/kg once every two weeks.
Cidofovir: Three groups:
1. the deferral group, treatment deferred until retinitis progressed
2. Low-dose cidofovir group, 5 mg/kg of body weight once weekly for two weeks, then maintenance therapy with cidofovir, 3mg/kg once every 2 weeks.
3. High-dose cidofovir group, 5mg/kg once weekly for 2 weeks, then maintenance therapy with cidofovir, 5mg/kg once every two weeks. | 26 |
| Cidofovir (Low Dose) 5 mg/kg IV (in the vein) of body weight once weekly for two weeks, then maintenance therapy with cidofovir, 3mg/kg once every 2 weeks
Cidofovir: Three groups:
1. the deferral group, treatment deferred until retinitis progressed
2. Low-dose cidofovir group, 5 mg/kg of body weight once weekly for two weeks, then maintenance therapy with cidofovir, 3mg/kg once every 2 weeks.
3. High-dose cidofovir group, 5mg/kg once weekly for 2 weeks, then maintenance therapy with cidofovir, 5mg/kg once every two weeks. | 26 |
| Cidofovir (High Dose) 5mg/kg IV (in the vein) once weekly for 2 weeks, then maintenance therapy with cidofovir, 5mg/kg once every two weeks.
Cidofovir: Three groups:
1. the deferral group, treatment deferred until retinitis progressed
2. Low-dose cidofovir group, 5 mg/kg of body weight once weekly for two weeks, then maintenance therapy with cidofovir, 3mg/kg once every 2 weeks.
3. High-dose cidofovir group, 5mg/kg once weekly for 2 weeks, then maintenance therapy with cidofovir, 5mg/kg once every two weeks. | 12 |
| Total | 64 |
Baseline characteristics
| Characteristic | Treatment Deferral | Cidofovir (Low Dose) | Cidofovir (High Dose) | 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 | 26 Participants | 26 Participants | 12 Participants | 64 Participants |
| Sex: Female, Male Female | 2 Participants | 2 Participants | 1 Participants | 5 Participants |
| Sex: Female, Male Male | 24 Participants | 24 Participants | 11 Participants | 59 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 | 0 / 26 | 2 / 26 | 2 / 12 |
| serious Total, serious adverse events | 3 / 26 | 13 / 26 | 8 / 12 |
Outcome results
Primary
Survival
Time frame: All patients enrolled will be followed until a common study closing date
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Treatment Deferral | Survival | progression | 20 participants |
| Treatment Deferral | Survival | mortality | 6 participants |
| Treatment Deferral | Survival | va loss of 15 letters | 4 participants |
| Cidofovir (Low Dose) | Survival | progression | 17 participants |
| Cidofovir (Low Dose) | Survival | mortality | 7 participants |
| Cidofovir (Low Dose) | Survival | va loss of 15 letters | 6 participants |
| Cidofovir (High Dose) | Survival | mortality | 3 participants |
| Cidofovir (High Dose) | Survival | va loss of 15 letters | 2 participants |
| Cidofovir (High Dose) | Survival | progression | 5 participants |