- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00000142
Studies of the Ocular Complications of AIDS (SOCA)--HPMPC Peripheral CMV Retinitis Trial (HPCRT) (HPCRT)
Study Overview
Status
Conditions
Intervention / Treatment
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.
Study Type
Enrollment (Actual)
Phase
- Phase 2
- Phase 3
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: 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. |
Three groups:
Other Names:
|
Experimental: 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
|
Three groups:
Other Names:
|
Experimental: 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.
|
Three groups:
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Survival
Time Frame: All patients enrolled will be followed until a common study closing date
|
All patients enrolled will be followed until a common study closing date
|
Collaborators and Investigators
Collaborators
Investigators
- Study Chair: Douglas Jabs, MD, Icahn School of Medicine at Mount Sinai
Publications and helpful links
General Publications
- Holland GN, Van Natta ML, Goldenberg DT, Ritts R Jr, Danis RP, Jabs DA; Studies of Ocular Complications of AIDS Research Group. Relationship Between Opacity of Cytomegalovirus Retinitis Lesion Borders and Severity of Immunodeficiency Among People With AIDS. Invest Ophthalmol Vis Sci. 2019 May 1;60(6):1853-1862. doi: 10.1167/iovs.18-26517.
- Parenteral cidofovir for cytomegalovirus retinitis in patients with AIDS: the HPMPC peripheral cytomegalovirus retinitis trial. A randomized, controlled trial. Studies of Ocular complications of AIDS Research Group in Collaboration with the AIDS Clinical Trials Group. Ann Intern Med. 1997 Feb 15;126(4):264-74. doi: 10.7326/0003-4819-126-4-199702150-00002.
- Long-term follow-up of patients with AIDS treated with parenteral cidofovir for cytomegalovirus retinitis: the HPMPC Peripheral Cytomegalovirus Retinitis Trial. The Studies of Ocular Complications of AIDS Research Group in collaboration with the AIDS Clinical Trials Group. AIDS. 2000 Jul 28;14(11):1571-81.
- Kravcik S. Cidofovir for cytomegalovirus retinitis. Ann Intern Med. 1997 Sep 15;127(6):490-1. doi: 10.7326/0003-4819-127-6-199709150-00015. No abstract available.
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Virus Diseases
- Infections
- Eye Diseases
- Retinal Diseases
- DNA Virus Infections
- Herpesviridae Infections
- Eye Infections
- Eye Infections, Viral
- Cytomegalovirus Infections
- Retinitis
- Cytomegalovirus Retinitis
- Molecular Mechanisms of Pharmacological Action
- Anti-Infective Agents
- Antiviral Agents
- Enzyme Inhibitors
- Cidofovir
Other Study ID Numbers
- NEI-41
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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