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

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

Study Overview

Status

Completed

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

Interventional

Enrollment (Actual)

64

Phase

  • Phase 2
  • Phase 3

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

13 years and older (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

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

This section provides details of the study plan, including how the study is designed and what the study is measuring.

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:

  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.
Other Names:
  • 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

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.
Other Names:
  • 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.

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.
Other Names:
  • Vistide

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

This is where you will find people and organizations involved with this study.

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

April 1, 1994

Primary Completion (Actual)

February 1, 1996

Study Completion (Actual)

February 1, 1996

Study Registration Dates

First Submitted

September 23, 1999

First Submitted That Met QC Criteria

September 23, 1999

First Posted (Estimate)

September 24, 1999

Study Record Updates

Last Update Posted (Estimate)

November 17, 2015

Last Update Submitted That Met QC Criteria

October 14, 2015

Last Verified

July 1, 2015

More Information

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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