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

Primary Purpose

HIV Infections, CMV Cytomegalovirus Retinitis

Status
Completed
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
Cidofovir
Sponsored by
Johns Hopkins Bloomberg School of Public Health
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for HIV Infections

Eligibility Criteria

13 Years - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm 3

    Arm Type

    Experimental

    Experimental

    Experimental

    Arm Label

    treatment deferral

    Cidofovir (low dose)

    Cidofovir (high dose)

    Arm Description

    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.

    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

    5mg/kg IV (in the vein) once weekly for 2 weeks, then maintenance therapy with cidofovir, 5mg/kg once every two weeks.

    Outcomes

    Primary Outcome Measures

    Survival

    Secondary Outcome Measures

    Full Information

    First Posted
    September 23, 1999
    Last Updated
    October 14, 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
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    1. Study Identification

    Unique Protocol Identification Number
    NCT00000142
    Brief Title
    Studies of the Ocular Complications of AIDS (SOCA)--HPMPC Peripheral CMV Retinitis Trial (HPCRT)
    Acronym
    HPCRT
    Official Title
    Studies of the Ocular Complications of AIDS (SOCA)--HPMPC Peripheral CMV Retinitis Trial (HPCRT)
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    July 2015
    Overall Recruitment Status
    Completed
    Study Start Date
    April 1994 (undefined)
    Primary Completion Date
    February 1996 (Actual)
    Study Completion Date
    February 1996 (Actual)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the 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

    4. Oversight

    Data Monitoring Committee
    Yes

    5. 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.
    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.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    HIV Infections, CMV Cytomegalovirus Retinitis

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 2, Phase 3
    Interventional Study Model
    Parallel Assignment
    Masking
    None (Open Label)
    Allocation
    Randomized
    Enrollment
    64 (Actual)

    8. Arms, Groups, and Interventions

    Arm Title
    treatment deferral
    Arm Type
    Experimental
    Arm Description
    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.
    Arm Title
    Cidofovir (low dose)
    Arm Type
    Experimental
    Arm Description
    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
    Arm Title
    Cidofovir (high dose)
    Arm Type
    Experimental
    Arm Description
    5mg/kg IV (in the vein) once weekly for 2 weeks, then maintenance therapy with cidofovir, 5mg/kg once every two weeks.
    Intervention Type
    Drug
    Intervention Name(s)
    Cidofovir
    Other Intervention Name(s)
    Vistide
    Intervention Description
    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.
    Primary Outcome Measure Information:
    Title
    Survival
    Time Frame
    All patients enrolled will be followed until a common study closing date

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    13 Years
    Accepts Healthy Volunteers
    No
    Eligibility 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.
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Douglas Jabs, MD
    Organizational Affiliation
    Icahn School of Medicine at Mount Sinai
    Official's Role
    Study Chair

    12. IPD Sharing Statement

    Citations:
    PubMed Identifier
    9036798
    Citation
    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.
    Results Reference
    background
    PubMed Identifier
    10983644
    Citation
    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.
    Results Reference
    background
    PubMed Identifier
    9313009
    Citation
    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.
    Results Reference
    background
    PubMed Identifier
    31042791
    Citation
    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.
    Results Reference
    derived

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