Studies of the Ocular Complications of AIDS (SOCA)--Foscarnet-Ganciclovir CMV Retinitis Trial (FGCRT)

• Sponsor: Johns Hopkins Bloomberg School of Public Health (Other)
• Overall Status: Completed
• CT.gov ID: NCT00000136
• Collaborator: National Eye Institute (NEI) (NIH), Johns Hopkins University (Other), University of Wisconsin, Madison (Other), Baylor College of Medicine (Other), Louisiana State University Health Sciences Center in New Orleans (Other), New York Presbyterian Hospital (Other), Icahn School of Medicine at Mount Sinai (Other), NYU Langone Health (Other), Northwestern University (Other), University of California, Los Angeles (Other), University of California, San Diego (Other), University of California, San Francisco (Other), University of Miami (Other), University of Massachusetts, Worcester (Other), Memorial Sloan Kettering Cancer Center (Other)
• Enrollment: 234
• Arms: 2
• Duration (Months): 19

Study Details

Study Description

Brief Summary

To evaluate the relative safety and efficacy of ganciclovir and foscarnet as initial treatment of patients with cytomegalovirus (CMV) retinitis.

Condition or Disease	Intervention/Treatment	Phase
HIV Infections; Cytomegalovirus Retinitis	Drug: Foscarnet; Drug: Ganciclovir	Phase 3

Detailed Description

CMV retinitis is the most common intraocular infection in patients with AIDS and is estimated to affect 35 to 40 percent of patients with AIDS. Untreated CMV retinitis is a progressive disorder, the end result of which is total retinal destruction and blindness. The first two drugs approved by the United States Food and Drug Administration (FDA) for the treatment of CMV retinitis were ganciclovir (Cytovene) and foscarnet (Foscavir). At the time of this trial, both ganciclovir and foscarnet were available only as intravenous formulations. Both drugs were given in a similar two-step fashion: an initial 2-week course of high-dose therapy (induction) to control the infection followed by long-term lower dose therapy to prevent relapse (maintenance). The FGCRT compared foscarnet and ganciclovir as initial therapy for CMV retinitis.

The FGCRT was a multicenter, randomized, controlled clinical trial comparing foscarnet and ganciclovir as initial therapy for CMV retinitis. Patients with previously untreated CMV retinitis were randomized to therapy with either intravenous ganciclovir or intravenous foscarnet. The outcome measures of this trial were survival, retinitis progression, loss of visual function (visual acuity and visual field), and morbidity.

Study Design

• Study Type: Interventional
• Actual Enrollment: 234 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Foscarnet-Ganciclovir CMV Retinitis Trial
• Study Start Date: Mar 1, 1990
• Actual Primary Completion Date: Oct 1, 1991
• Actual Study Completion Date: Oct 1, 1991

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Foscarnet The induction dose for foscarnet is 60 mg/kg every 8 hours. Full dose maintenance therapy for foscarnet is 90 mg/kg/day	Drug: Foscarnet; 60 mg/kg every 8 hours, 90 mg/kg/day; Other Names: Foscavir ; Drug: Ganciclovir; 5 mg/kg every 12 hours, 5 mg/kg every 24 hours; Other Names: Vitraset
Experimental: Ganciclovir The induction dose for ganciclovir is 5 mg/kg every 12 hours. Full dose maintenance therapy for ganciclovir is 5 mg/kg every 24 hours, 7 days a week.	Drug: Foscarnet; 60 mg/kg every 8 hours, 90 mg/kg/day; Other Names: Foscavir ; Drug: Ganciclovir; 5 mg/kg every 12 hours, 5 mg/kg every 24 hours; Other Names: Vitraset

Outcome Measures

Primary Outcome Measures

1. Mortality [All patients enrolled will be followed until a common study closing date, which was chosen to provide a minimum of 1 year of follow-up for all patients enrolled in the trial.]

Eligibility Criteria

Criteria

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

Inclusion criteria:

• CMV retinitis in one or both eyes

• At least 1/4 disk are of one CMV lesion photographable

• Diagnosis of AIDS as defined by Center for Disease Control criteria or documented HIV infection

• Age 13 and greater

• Visual acuity ≥ 3/200 in at least one eye diagnosed with CMV retinitis

• Absolute neutrophil count ≥ 1,000 cells/µl

• Platelet ≥ 25,000 cells/µl

• Serum creatinine ≥ 2.0 mg/dl

• Karnofsky score ≥ 60

• Informed consent

Exclusion criteria:

• Previous treatment of CMV retinitis

• Treatment with anti-CMV therapy for an extra-ocular CMV infection currently or in the past 28 days

• Known or suspected allergy to study drugs

• Pregnant or Lactating

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• Johns Hopkins Bloomberg School of Public Health
• National Eye Institute (NEI)
• Johns Hopkins University
• University of Wisconsin, Madison
• Baylor College of Medicine
• Louisiana State University Health Sciences Center in New Orleans
• New York Presbyterian Hospital
• Icahn School of Medicine at Mount Sinai
• NYU Langone Health
• Northwestern University
• University of California, Los Angeles
• University of California, San Diego
• University of California, San Francisco
• University of Miami
• University of Massachusetts, Worcester
• Memorial Sloan Kettering Cancer Center

Investigators

• Principal Investigator: Curtis Meinert, PhD, Johns Hopkins University

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• http://www.nei.nih.gov/news/pressreleases/fgcrtpressrelease.asp

Publications

• Antiviral effects of foscarnet and ganciclovir therapy on human immunodeficiency virus p24 antigen in patients with AIDS and cytomegalovirus retinitis. Studies of Ocular Complications of AIDS Research Group in collaboration with AIDS Clinical Trials Group. J Infect Dis. 1995 Sep;172(3):613-21.
• Assessment of cytomegalovirus retinitis. Clinical evaluation vs centralized grading of fundus photographs. Studies of Ocular Complications of AIDS Research Group, AIDS Clinical Trials Group. Arch Ophthalmol. 1996 Jul;114(7):791-805.
• Clinical vs photographic assessment of treatment of cytomegalovirus retinitis. Foscarnet-Ganciclovir Cytomegalovirus Retinitis Trial Report 8. Studies of Ocular Complications of AIDS Research Group, AIDS Clinical Trials Group. Arch Ophthalmol. 1996 Jul;114(7):848-55.
• Cytomegalovirus (CMV) culture results, drug resistance, and clinical outcome in patients with AIDS and CMV retinitis treated with foscarnet or ganciclovir. Studies of Ocular Complications of AIDS (SOCA) in collaboration with the AIDS Clinical Trial Group. J Infect Dis. 1997 Jul;176(1):50-8.
• Foscarnet-Ganciclovir Cytomegalovirus Retinitis Trial. 4. Visual outcomes. Studies of Ocular Complications of AIDS Research Group in collaboration with the AIDS Clinical Trials Group. Ophthalmology. 1994 Jul;101(7):1250-61.
• Foscarnet-Ganciclovir Cytomegalovirus Retinitis Trial: 5. Clinical features of cytomegalovirus retinitis at diagnosis. Studies of ocular complications of AIDS Research Group in collaboration with the AIDS Clinical Trials Group. Am J Ophthalmol. 1997 Aug;124(2):141-57.
• Holbrook JT, Davis MD, Hubbard LD, Martin BK, Holland GN, Jabs DA, Gilpin AK, Meinert C, Reshef DS. Risk factors for advancement of cytomegalovirus retinitis in patients with acquired immunodeficiency syndrome. Studies of Ocular Complications of AIDS Research Group. Arch Ophthalmol. 2000 Sep;118(9):1196-204.
• Morbidity and toxic effects associated with ganciclovir or foscarnet therapy in a randomized cytomegalovirus retinitis trial. Studies of ocular complications of AIDS Research Group, in collaboration with the AIDS Clinical Trials Group. Arch Intern Med. 1995 Jan 9;155(1):65-74.
• Rhegmatogenous retinal detachment in patients with cytomegalovirus retinitis: the Foscarnet-Ganciclovir Cytomegalovirus Retinitis Trial. The Studies of Ocular Complications of AIDS (SOCA) Research Group in Collaboration with the AIDS Clinical Trials Group (ACTG). Am J Ophthalmol. 1997 Jul;124(1):61-70.
• Studies of ocular complications of AIDS Foscarnet-Ganciclovir Cytomegalovirus Retinitis Trial: 1. Rationale, design, and methods. AIDS Clinical Trials Group (ACTG). Control Clin Trials. 1992 Feb;13(1):22-39.
• Studies of Ocular Complications of AIDS Research Group; AIDS Clinical Trials Group. Mortality in patients with the acquired immunodeficiency syndrome treated with either foscarnet or ganciclovir for cytomegalovirus retinitis. N Engl J Med. 1992 Jan 23;326(4):213-20. Erratum in: N Engl J Med 1992 Apr 23;326(17):1172.
• Wu AW, Coleson LC, Holbrook J, Jabs DA. Measuring visual function and quality of life in patients with cytomegalovirus retinitis. Development of a questionnaire. Studies of Ocular Complication of AIDS Research Group. Arch Ophthalmol. 1996 Jul;114(7):841-7.
• Wu AW, Revicki DA, Jacobson D, Malitz FE. Evidence for reliability, validity and usefulness of the Medical Outcomes Study HIV Health Survey (MOS-HIV). Qual Life Res. 1997 Aug;6(6):481-93. Review.

• Responsible Party: Johns Hopkins Bloomberg School of Public Health
• ClinicalTrials.gov Identifier: NCT00000136
• Other Study ID Numbers: NEI-35; U10EY008057
• First Posted: Sep 24, 1999
• Last Update Posted: Oct 22, 2015
• Last Verified: Jul 1, 2015

• Additional relevant MeSH terms: Cytomegalovirus Retinitis; Retinitis; Ganciclovir; Ganciclovir triphosphate; Foscarnet

Study Results

Participant Flow

Arm/Group Title	Foscarnet	Ganciclovir
Arm/Group Description	The induction dose for foscarnet is 60 mg/kg every 8 hours. Full dose maintenance therapy for foscarnet is 90 mg/kg/day Foscarnet: 60 mg/kg every 8 hours, 90 mg/kg/day Ganciclovir: 5 mg/kg every 12 hours, 5 mg/kg every 24 hours	The induction dose for ganciclovir is 5 mg/kg every 12 hours. Full dose maintenance therapy for ganciclovir is 5 mg/kg every 24 hours, 7 days a week. Foscarnet: 60 mg/kg every 8 hours, 90 mg/kg/day Ganciclovir: 5 mg/kg every 12 hours, 5 mg/kg every 24 hours
Period Title: Overall Study
STARTED	107	127
COMPLETED	107	127
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Foscarnet	Ganciclovir	Total
Arm/Group Description	The induction dose for foscarnet is 60 mg/kg every 8 hours. Full dose maintenance therapy for foscarnet is 90 mg/kg/day Foscarnet: 60 mg/kg every 8 hours, 90 mg/kg/day Ganciclovir: 5 mg/kg every 12 hours, 5 mg/kg every 24 hours	The induction dose for ganciclovir is 5 mg/kg every 12 hours. Full dose maintenance therapy for ganciclovir is 5 mg/kg every 24 hours, 7 days a week. Foscarnet: 60 mg/kg every 8 hours, 90 mg/kg/day Ganciclovir: 5 mg/kg every 12 hours, 5 mg/kg every 24 hours	Total of all reporting groups
Overall Participants	107	127	234
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	107 100%	127 100%	234 100%
>=65 years	0 0%	0 0%	0 0%
Sex: Female, Male (Count of Participants)
Female	9 8.4%	11 8.7%	20 8.5%
Male	98 91.6%	116 91.3%	214 91.5%
Region of Enrollment (participants) [Number]
United States	107 100%	127 100%	234 100%

Outcome Measures

1. Primary Outcome

Title	Mortality
Time Frame	All patients enrolled will be followed until a common study closing date, which was chosen to provide a minimum of 1 year of follow-up for all patients enrolled in the trial.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Foscarnet	Ganciclovir
Arm/Group Description	The induction dose for foscarnet is 60 mg/kg every 8 hours. Full dose maintenance therapy for foscarnet is 90 mg/kg/day Foscarnet: 60 mg/kg every 8 hours, 90 mg/kg/day Ganciclovir: 5 mg/kg every 12 hours, 5 mg/kg every 24 hours	The induction dose for ganciclovir is 5 mg/kg every 12 hours. Full dose maintenance therapy for ganciclovir is 5 mg/kg every 24 hours, 7 days a week. Foscarnet: 60 mg/kg every 8 hours, 90 mg/kg/day Ganciclovir: 5 mg/kg every 12 hours, 5 mg/kg every 24 hours
Measure Participants	107	127
Number [participants]	107 100%	127 100%

Adverse Events

Time Frame	1 year, 7 months
Arm/Group Title	Foscarnet		Ganciclovir
Arm/Group Description	The induction dose for foscarnet is 60 mg/kg every 8 hours. Full dose maintenance therapy for foscarnet is 90 mg/kg/day Foscarnet: 60 mg/kg every 8 hours, 90 mg/kg/day Ganciclovir: 5 mg/kg every 12 hours, 5 mg/kg every 24 hours		The induction dose for ganciclovir is 5 mg/kg every 12 hours. Full dose maintenance therapy for ganciclovir is 5 mg/kg every 24 hours, 7 days a week. Foscarnet: 60 mg/kg every 8 hours, 90 mg/kg/day Ganciclovir: 5 mg/kg every 12 hours, 5 mg/kg every 24 hours
All Cause Mortality
	Foscarnet		Ganciclovir
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Foscarnet		Ganciclovir
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	60/107 (56.1%)		73/127 (57.5%)
Immune system disorders
Opportunistic Infection	60/107 (56.1%)	153	73/127 (57.5%)	180
Other (Not Including Serious) Adverse Events
	Foscarnet		Ganciclovir
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/107 (0%)		0/127 (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.