Studies of Ocular Complications of AIDS (SOCA)--Ganciclovir-Cidofovir CMV Retinitis Trial (GCCRT)

Studies of Ocular Complications of AIDS (SOCA)--Ganciclovir-Cidofovir CMV Retinitis Trial (GCCRT)



Sponsors


Source

Johns Hopkins Bloomberg School of Public Health

Oversight Info

Has Dmc

Yes


Brief Summary

To compare the newest CMV retinitis drug, cidofovir, with a regimen of the ganciclovir
intraocular device plus oral ganciclovir with respect to efficacy in preventing vision loss.

To compare a treatment regimen that incorporates highly active local therapy (ganciclovir
device) with a treatment regimen that does not.

Detailed Description

Cytomegalovirus (CMV) is among the most frequently encountered opportunistic infections in
patients with AIDS. In the era of prophylaxis for pneumocystic pneumonia, CMV disease is
estimated to affect 45 percent of patients with AIDS sometime between the diagnosis of AIDS
and death. Retinitis has been estimated to account for up to 85 percent of CMV disease in
these patients, making CMV retinitis the most common ocular infection encountered. CMV
retinitis is a relatively late-stage manifestation, associated with cluster of
differentiation 4 (CD4) + T-cell counts < 100 cells/µL and often < 50 cells/µL.

All currently available treatments for CMV suppress viral replication but do not eliminate
the virus from the body. Discontinuation of therapy is associated with a prompt relapse of
the retinitis. Despite the use of chronic suppressive therapy, relapse of the retinitis
generally occurs, at least with systemically administered anti-CMV drugs.

The first two treatments approved for CMV retinitis were intravenous ganciclovir and
intravenous foscarnet. Both are given by daily intravenous infusions and therefore require
central venous catheters. The development of newer treatments has focused not only on
efficacious treatments, but also on treatments that do not require central venous catheters.
Available treatments now include oral ganciclovir, the ganciclovir intraocular device, and
intravenous cidofovir.

In vitro data suggest that combination therapies are synergistic in inhibiting viral
replication; these therapies include a foscarnet-ganciclovir combination and a
cidofovir-ganciclovir combination. In the SOCA--CMV Retinitis Retreatment Trial, the
combination of intravenous ganciclovir and foscarnet was more effective than either drug
alone for the treatment of relapsed retinitis. Therefore, the combination of intermittent
intravenous cidofovir and daily oral ganciclovir may be an attractive therapy for relapsed
disease because it may provide synergy for controlling both ocular and visceral disease while
not necessitating either a central venous catheter or an intraocular surgical procedure.

The Ganciclovir-Cidofovir CMV Retinitis Trial (GCCRT) is a randomized, multicenter clinical
trial. Patients will be assigned to receive one of two regimens: (1) ganciclovir intraocular
device plus oral ganciclovir or (2) intravenous cidofovir. The intraocular device will be
surgically implanted at baseline and again every 6 to 8 months in eyes with CMV retinitis.
Oral ganciclovir is taken at a dose of 1 gram three times daily. Cidofovir will be
administered intravenously at 5 mg/kg once weekly for 2 consecutive weeks and once every 2
weeks thereafter. If disease progression occurs in patients receiving cidofovir, patients
will be given reinduction therapy, and oral ganciclovir at a dose of 1 gram three times per
day will be added to the treatment. If patients assigned to cidofovir are unable to tolerate
that regimen, an alternative systemic regimen will be recommended.

Study outcome variables include a decrease of three or more lines from baseline in best
corrected visual acuity and rate of visual field loss. The study will also assess other
variables including mortality, blood CMV and HIV load, quality of life, and medical costs.

Treatment assignment will not be masked to either patients or clinicians; however, reading of
fundus photographs to determine both change in retinal involvement and progression will be
masked.

Overall Status

Completed

Start Date

1997-05-01

Completion Date

2000-06-01

Primary Completion Date

2000-06-01

Phase

Phase 3

Study Type

Interventional

Primary Outcome

Measure

Time Frame

Survival
3 years

Enrollment

61

Conditions


Intervention

Intervention Type

Device

Intervention Name


Description

oral ganciclovir, 1 gm three times daily

Arm Group Label

Ganciclovir implant and oral ganciclovir

Other Name

Vitraset


Intervention Type

Drug

Intervention Name


Description

intravenous, 5 mg/kg once weekly for two doses, followed by 5 mg/kg every other week

Arm Group Label

Cidofovir IV (Intravenous)

Other Name

Vistide



Eligibility

Criteria

Inclusion criteria:

- Age 13 years or older

- Diagnosis of AIDS according to current Centers for Disease Control and Prevention
(CDC) definition

- Diagnosis of active CMV retinitis by a SOCA-certified ophthalmologist (involvement of
any zone or amount of retina is allowed)

- Best corrected visual acuity of 20/100 or better in at least one eye

- At least one lesion 750 cells/µL or greater

- Platelet count 50,000 cells/µL or greater

- Willingness and ability, with the assistance of a caregiver if necessary to comply
with treatment and follow up procedures

- Willingness of all men and women of childbearing potential to practice adequate birth
control to prevent pregnancies during the study and for 3 months afterwards

- Collection of all baseline data within 5 days prior to randomization

- Signed consent statement

Exclusion criteria:

- Media opacities that preclude visualization of the fundus of all otherwise eligible
eyes

- Treatment for CMV retinitis with the ganciclovir intraocular implant within 9 months
of study entry

- Medical problems or drug or alcohol abuse sufficient to hinder adherence to treatment
or follow up procedures

- Unwillingness to refrain from breast-feeding during the study and for 3 months
afterwards

Gender

All

Minimum Age

13 Years

Maximum Age

N/A

Healthy Volunteers

No


Overall Official

Last Name

Role

Affiliation

Douglas Jabs, MD
Study Chair
SOCA Chairman's Office

Location

Facility

Department of Ophthalmology, University of California, Irvine
Irvine California 92697-4375 United States
Shiley Eye Center Center, 0946, University of California, San Diego
La Jolla California 92093-0946 United States
LAC/USC Medical Center, 5P21 Rand Schrader Clinic
Los Angeles California 90033 United States
Jules Stein Eye Institute, University of California, Los Angeles
Los Angeles California 90095-7003 United States
Beckman Vision Center, University of California, San Francisco
San Francisco California 94143 United States
Bascom Palmer Eye Institute, University of Miami
Miami Florida 33136 United States
University of South Florida, MDC Box 21
Tampa Florida 33612-4799 United States
The Emory Clinic, Emory University
Atlanta Georgia 30322 United States
Department of Ophthalmology, Northwestern University
Chicago Illinois 60611 United States
Division of Infectious Diseases, Indiana University, Indianapolis
Indianapolis Indiana 46202-2879 United States
LSU Eye Center, Louisiana State University Medical Center
New Orleans Louisiana 70112 United States
The Wilmer Ophthalmological Institute, The Johns Hopkins University School of Medicine
Baltimore Maryland 21287-9217 United States
Harvard/BCH AIDS Clinical Trials Unit, Massachusetts General Hospital
Boston Massachusetts 02114 United States
UMDNJ-New Jersey Medical School
Newark New Jersey 07103-2499 United States
Department of Ophthalmology, New York University Medical Center
New York New York 10016 United States
Department of Ophthalmology, New York Hospital-Cornell Medical Center
New York New York 10021 United States
Department of Ophthalmology, Mount Sinai School of Medicine
New York New York 10029-6574 United States
University of North Carolina at Chapel Hill
Chapel Hill North Carolina 27599-7030 United States
Cullen Eye Institute, Baylor College of Medicine
Houston Texas 77030 United States

Location Countries

Country

United States


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

2

Intervention Browse

Mesh Term

Ganciclovir

Cidofovir

Ganciclovir triphosphate



Arm Group

Arm Group Label

Ganciclovir implant and oral ganciclovir

Arm Group Type

Experimental

Description

Ganciclovir device and oral dose of Ganciclovir 1 gm three times daily


Arm Group Label

Cidofovir IV (Intravenous)

Arm Group Type

Experimental

Description

cidofovir intravenous (IV) start off with 5 mg/kg once weekly for two doses then followed by 5 mg/kg every other week



Firstreceived Results Date

N/A

Reference

Citation

Studies of Ocular Complications of AIDS Research Group. The AIDS Clinical Trials Group. The ganciclovir implant plus oral ganciclovir versus parenteral cidofovir for the treatment of cytomegalovirus retinitis in patients with acquired immunodeficiency syndrome: The Ganciclovir Cidofovir Cytomegalovirus Retinitis Trial. Am J Ophthalmol. 2001 Apr;131(4):457-67.

PMID

11292409


Citation

Dunn JP, Van Natta M, Foster G, Kuppermann BD, Martin DF, Zong A, Jabs DA; Studies of Ocular Complications of AIDS Research Group. Complications of ganciclovir implant surgery in patients with cytomegalovirus retinitis: the Ganciclovir Cidofovir Cytomegalovirus Retinitis Trial. Retina. 2004 Feb;24(1):41-50.

PMID

15076943



Acronym

GCCRT

Patient Data

Sharing Ipd

Yes


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

February 18, 2016

Last Update Submitted Qc

February 18, 2016

Last Update Posted

March 14, 2016

Results First Submitted

July 1, 2015

Results First Submitted Qc

February 18, 2016

Results First Posted

March 14, 2016


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.



© 2018 ICH GCP