Studies of the Ocular Complications of AIDS (SOCA)--HPMPC Peripheral CMV Retinitis Trial (HPCRT) (HPCRT)

• ClinicalTrials.gov Identifier: NCT00000142
• Recruitment Status: Completed
• First Posted: September 24, 1999
• Results First Posted: November 17, 2015
• Last Update Posted: November 17, 2015
• Sponsor: Johns Hopkins Bloomberg School of Public Health
• Collaborators: 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
• Information provided by (Responsible Party): Johns Hopkins Bloomberg School of Public Health

Study Description

Brief Summary:

To test and evaluate the efficacy and safety of intravenous cidofovir (Vistide, previously known as HPMPC) for the treatment of retinitis.

Condition or disease	Intervention/treatment	Phase
HIV Infections; CMV Cytomegalovirus Retinitis	Drug: Cidofovir	Phase 2; Phase 3

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 64 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Studies of the Ocular Complications of AIDS (SOCA)--HPMPC Peripheral CMV Retinitis Trial (HPCRT)
• Study Start Date: April 1994
• Actual Primary Completion Date: February 1996
• Actual Study Completion Date: February 1996

Arms and Interventions

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.	Drug: Cidofovir; Three groups: the deferral group, treatment deferred until retinitis progressed; 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.; High-dose cidofovir group, 5mg/kg once weekly for 2 weeks, then maintenance therapy with cidofovir, 5mg/kg once every two weeks.; Other Name: Vistide
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	Drug: Cidofovir; Three groups: the deferral group, treatment deferred until retinitis progressed; 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.; High-dose cidofovir group, 5mg/kg once weekly for 2 weeks, then maintenance therapy with cidofovir, 5mg/kg once every two weeks.; Other Name: Vistide
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.	Drug: Cidofovir; Three groups: the deferral group, treatment deferred until retinitis progressed; 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.; High-dose cidofovir group, 5mg/kg once weekly for 2 weeks, then maintenance therapy with cidofovir, 5mg/kg once every two weeks.; Other Name: Vistide

Outcome Measures

Primary Outcome Measures :

1. Survival [ Time Frame: All patients enrolled will be followed until a common study closing date ]

Eligibility Criteria

• Ages Eligible for Study: 13 Years and older (Child, Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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.

Contacts and Locations

Sponsors and Collaborators

Johns Hopkins Bloomberg School of Public Health

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

Investigators

• Study Chair: Douglas Jabs, MD; Icahn School of Medicine at Mount Sinai

More Information

Publications:

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.

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.

Jabs DA, Meinert CL, Lalezari JP. Letter to the Editor (response) regarding cidofovir for cytomegalovirus retinitis (HPCRT). Ann Int Med. 1997;127:490-491.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: Johns Hopkins Bloomberg School of Public Health
• ClinicalTrials.gov Identifier: NCT00000142 History of Changes
• Other Study ID Numbers: NEI-41
• First Posted: September 24, 1999
• Results First Posted: November 17, 2015
• Last Update Posted: November 17, 2015
• Last Verified: July 2015

Additional relevant MeSH terms:

Cytomegalovirus Retinitis; Retinitis; Virus Diseases; Retinal Diseases; Eye Diseases; Cytomegalovirus Infections; Herpesviridae Infections; DNA Virus Infections; Eye Infections, Viral; Eye Infections; Cidofovir; Antiviral Agents; Anti-Infective Agents; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action