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

• Sponsor: Johns Hopkins Bloomberg School of Public Health (Other)
• Overall Status: Completed
• CT.gov ID: NCT00000143
• Collaborator: (none)
• Enrollment: 61
• Locations: 19
• Arms: 2
• Duration (Months): 37
• Patients Per Site: 3.2
• Patients Per Site Per Month: 0.1

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Cytomegalovirus Retinitis; HIV Infections	Device: Ganciclovir implant and oral ganciclovir; Drug: Cidofovir intravenous	Phase 3

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 61 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Studies of Ocular Complications of AIDS (SOCA)--Ganciclovir-Cidofovir CMV Retinitis Trial (GCCRT)
• Study Start Date: May 1, 1997
• Actual Primary Completion Date: Jun 1, 2000
• Actual Study Completion Date: Jun 1, 2000

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Ganciclovir implant and oral ganciclovir Ganciclovir device and oral dose of Ganciclovir 1 gm three times daily	Device: Ganciclovir implant and oral ganciclovir; oral ganciclovir, 1 gm three times daily; Other Names: Vitraset
Experimental: Cidofovir IV (Intravenous) cidofovir intravenous (IV) start off with 5 mg/kg once weekly for two doses then followed by 5 mg/kg every other week	Drug: Cidofovir intravenous; intravenous, 5 mg/kg once weekly for two doses, followed by 5 mg/kg every other week; Other Names: Vistide

Outcome Measures

Primary Outcome Measures

1. Survival [3 years]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 13 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

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

Sponsors and Collaborators

• Johns Hopkins Bloomberg School of Public Health

Investigators

• Study Chair: Douglas Jabs, MD, SOCA Chairman's Office

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Other Studies of the Ocular Complications of AIDS (SOCA)]

Publications

• 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.
• 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.

• Responsible Party: Johns Hopkins Bloomberg School of Public Health
• ClinicalTrials.gov Identifier: NCT00000143
• Other Study ID Numbers: NEI-42
• First Posted: Sep 24, 1999
• Last Update Posted: Mar 14, 2016
• Last Verified: Jul 1, 2015

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Additional relevant MeSH terms: Cytomegalovirus Retinitis; Retinitis; Ganciclovir; Ganciclovir triphosphate; Cidofovir

Study Results

Participant Flow

Recruitment Details	June 1997

Arm/Group Title	Ganciclovir Implant and Oral Ganciclovir	Cidofovir IV (Intravenous)
Arm/Group Description	Ganciclovir device and oral dose of Ganciclovir 1 gm three times daily Ganciclovir implant and oral ganciclovir: oral ganciclovir, 1 gm three times daily	cidofovir intravenous (IV) start off with 5 mg/kg once weekly for two doses then followed by 5 mg/kg every other week Cidofovir intravenous: intravenous, 5 mg/kg once weekly for two doses, followed by 5 mg/kg every other week
Period Title: Overall Study
STARTED	31	30
COMPLETED	31	30
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Ganciclovir Implant and Oral Ganciclovir	Cidofovir IV (Intravenous)	Total
Arm/Group Description	Ganciclovir device and oral dose of Ganciclovir 1 gm three times daily Ganciclovir implant and oral ganciclovir: oral ganciclovir, 1 gm three times daily	cidofovir intravenous (IV) start off with 5 mg/kg once weekly for two doses then followed by 5 mg/kg every other week Cidofovir intravenous: intravenous, 5 mg/kg once weekly for two doses, followed by 5 mg/kg every other week	Total of all reporting groups
Overall Participants	31	30	61
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	31 100%	30 100%	61 100%
>=65 years	0 0%	0 0%	0 0%
Sex: Female, Male (Count of Participants)
Female	7 22.6%	5 16.7%	12 19.7%
Male	24 77.4%	25 83.3%	49 80.3%
Region of Enrollment (participants) [Number]
United States	31 100%	30 100%	61 100%

Outcome Measures

1. Primary Outcome

Title	Survival
Time Frame	3 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Ganciclovir Implant and Oral Ganciclovir	Cidofovir IV (Intravenous)
Arm/Group Description	Ganciclovir device and oral dose of Ganciclovir 1 gm three times daily Ganciclovir implant and oral ganciclovir: oral ganciclovir, 1 gm three times daily	cidofovir intravenous (IV) start off with 5 mg/kg once weekly for two doses then followed by 5 mg/kg every other week Cidofovir intravenous: intravenous, 5 mg/kg once weekly for two doses, followed by 5 mg/kg every other week
Measure Participants	31	30
Number [participants]	31 100%	30 100%

Adverse Events

Time Frame	3 years
Arm/Group Title	Ganciclovir Implant and Oral Ganciclovir		Cidofovir IV (Intravenous)
Arm/Group Description	Ganciclovir device and oral dose of Ganciclovir 1 gm three times daily Ganciclovir implant and oral ganciclovir: oral ganciclovir, 1 gm three times daily		cidofovir intravenous (IV) start off with 5 mg/kg once weekly for two doses then followed by 5 mg/kg every other week Cidofovir intravenous: intravenous, 5 mg/kg once weekly for two doses, followed by 5 mg/kg every other week
All Cause Mortality
	Ganciclovir Implant and Oral Ganciclovir		Cidofovir IV (Intravenous)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Ganciclovir Implant and Oral Ganciclovir		Cidofovir IV (Intravenous)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/31 (0%)		0/30 (0%)
Other (Not Including Serious) Adverse Events
	Ganciclovir Implant and Oral Ganciclovir		Cidofovir IV (Intravenous)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/31 (0%)		0/30 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.