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

HIV Infections Clinical Trial

— HPCRT  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00000142
• Other study ID #: NEI-41
• Status: Completed
• Phase: Phase 2/Phase 3
• First received: September 23, 1999
• Last updated: October 14, 2015
• Start date: April 1994
• Est. completion date: February 1996

Study information

• Verified date: July 2015
• Source: Johns Hopkins Bloomberg School of Public Health
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 64
• Est. completion date: February 1996
• Est. primary completion date: February 1996
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 13 Years and older

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• CMV Cytomegalovirus Retinitis
• Cytomegalovirus Retinitis
• HIV Infections
• Retinitis

Intervention

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.

Locations

Country	Name	City	State
n/a

Sponsors (14)

Lead Sponsor

Collaborator

Johns Hopkins Bloomberg School of Public Health

Baylor College of Medicine, Icahn School of Medicine at Mount Sinai, Johns Hopkins University, Louisiana State University Health Sciences Center in New Orleans, New Jersey Medical School, New York University School of Medicine, 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

References & Publications (3)

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

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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Survival		All patients enrolled will be followed until a common study closing date	Yes