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

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



Sponsors


Source

Johns Hopkins Bloomberg School of Public Health

Oversight Info

Has Dmc

Yes


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.

Overall Status

Completed

Start Date

1994-04-01

Completion Date

1996-02-01

Primary Completion Date

1996-02-01

Phase

Phase 2/Phase 3

Study Type

Interventional

Primary Outcome

Measure

Time Frame

Survival
All patients enrolled will be followed until a common study closing date

Enrollment

64

Conditions


Intervention

Intervention Type

Drug

Intervention Name


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.

Arm Group Label

treatment deferral

Cidofovir (low dose)

Cidofovir (high dose)


Other Name

Vistide


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.

Gender

All

Minimum Age

13 Years

Maximum Age

N/A

Healthy Volunteers

No


Overall Official

Last Name

Role

Affiliation

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

Verification Date

2015-07-01

Lastchanged Date

N/A

Firstreceived Date

N/A

Responsible Party

Responsible Party Type

Sponsor


Has Expanded Access

No

Condition Browse


Number Of Arms

3

Intervention Browse

Mesh Term

Cidofovir


Arm Group

Arm Group Label

treatment deferral

Arm Group Type

Experimental

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 Group Label

Cidofovir (low dose)

Arm Group Type

Experimental

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 Group Label

Cidofovir (high dose)

Arm Group Type

Experimental

Description

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



Firstreceived Results Date

N/A

Reference

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.

PMID

9036798


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.

PMID

10983644


Citation

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



Acronym

HPCRT

Firstreceived Results Disposition Date

N/A

Study Design Info

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary Purpose

Treatment

Masking

None (Open Label)


Study First Submitted

September 23, 1999

Study First Submitted Qc

September 23, 1999

Study First Posted

September 24, 1999

Last Update Submitted

October 14, 2015

Last Update Submitted Qc

October 14, 2015

Last Update Posted

November 17, 2015

Results First Submitted

June 2, 2015

Results First Submitted Qc

October 14, 2015

Results First Posted

November 17, 2015


ClinicalTrials.gov processed this data on August 24, 2018

Conditions

Conditions usually refer to a disease, disorder, syndrome, illness, or injury. In ClinicalTrials.gov, conditions include any health issue worth studying, such as lifespan, quality of life, health risks, etc.
Interventions

Interventions refer to the drug, vaccine, procedure, device, or other potential treatment being studied. Interventions can also include less intrusive possibilities such as surveys, education, and interviews.
Study Phase

Most clinical trials are designated as phase 1, 2, 3, or 4, based on the type of questions that study is seeking to answer:

In Phase 1 (Phase I) clinical trials, researchers test a new drug or treatment in a small group of people (20-80) for the first time to evaluate its safety, determine a safe dosage range, and identify side effects.

In Phase 2 (Phase II) clinical trials, the study drug or treatment is given to a larger group of people (100-300) to see if it is effective and to further evaluate its safety.

In Phase 3 (Phase III) clinical trials, the study drug or treatment is given to large groups of people (1,000-3,000) to confirm its effectiveness, monitor side effects, compare it to commonly used treatments, and collect information that will allow the drug or treatment to be used safely.

In Phase 4 (Phase IV) clinical trials, post marketing studies delineate additional information including the drug's risks, benefits, and optimal use.

These phases are defined by the Food and Drug Administration in the Code of Federal Regulations.



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