Studies of the Ocular Complications of AIDS (SOCA)--HPMPC... | NCT00000142

NCT00000142

Protocol Section

Identification Module

Results Section

Participant Flow Module

Annotation Section

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Document Section

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Derived Section

Miscellaneous Info Module

Status Module

Name	Class
Baylor College of Medicine	OTHER
Johns Hopkins University	OTHER
Louisiana State University Health Sciences Center in New Orleans	OTHER
Icahn School of Medicine at Mount Sinai

Description Module

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.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
treatment deferral	Experimental	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
Cidofovir (low dose)	Experimental	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
Cidofovir (high dose)	Experimental	5mg/kg IV (in the vein) once weekly for 2 weeks, then maintenance therapy with cidofovir, 5mg/kg once every two weeks.	Drug: Cidofovir

Interventions

Name	Type	Description	Arm Group Labels	Other Names
Cidofovir	Drug	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.

Measure	Description	Time Frame
Survival		All patients enrolled will be followed until a common study closing date

Eligibility Module

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.

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

PubMed Identifier	Type	Citation	Retractions
9036798	Background	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.
10983644

Arm/Group Information

ID	Title	Description
FG000	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. 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.
FG001	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 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.
FG002	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. 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.

Baseline Characteristics Module

Arm/Group Information

ID	Title	Description
BG000	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. 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.

Units	Counts
Participants	BG000

Baseline Measures

Title	Description	Population Description	Parameter Type	Dispersion Type	Unit of Measure	Calculate Percentage	Denominator Units Selected	Denominators	Classes
Age, Categorical			Count of Participants

Outcome Measures Module

Outcome Measures

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Survival

Posted

Number

participants

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

ID	Title	Description
OG000	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. 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.
OG001

Adverse Events Module

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	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. 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.

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
Proteinuria 2+	Blood and lymphatic system disorders		Non-systematic Assessment

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
Serum creatinine level >= 133 umol/L (1.5 mg/dL)	Blood and lymphatic system disorders		Non-systematic Assessment

ID	Term
D015658	HIV Infections
D017726	Cytomegalovirus Retinitis

ID	Term
D000086982	Blood-Borne Infections
D003141	Communicable Diseases
D007239	Infections
D015229	Sexually Transmitted Diseases, Viral

ID	Term
D063065	Organophosphonates
D009943	Organophosphorus Compounds
D009930	Organic Chemicals
D003596	Cytosine