Studies of the Ocular Complications of AIDS (SOCA)--Cytomegalovirus Retinitis Retreatment Trial (CRRT)

• Sponsor: Johns Hopkins Bloomberg School of Public Health (Other)
• Overall Status: Completed
• CT.gov ID: NCT00000134
• Collaborator: National Eye Institute (NEI) (NIH), National Institute of Allergy and Infectious Diseases (NIAID) (NIH), Johns Hopkins University (Other), University of Wisconsin, Madison (Other), Baylor College of Medicine (Other), Tulane University School of Medicine (Other), Icahn School of Medicine at Mount Sinai (Other), New York Presbyterian Hospital (Other), New York University (Other), Northwestern University (Other), University of California, Los Angeles (Other), University of California, San Francisco (Other), University of California, San Diego (Other), University of Miami (Other), University of North Carolina, Chapel Hill (Other), Memorial Sloan Kettering Cancer Center (Other)
• Enrollment: 279
• Arms: 3
• Duration (Months): 26.9

Study Details

Study Description

Brief Summary

To compare the relative merits of three therapeutic regimens in patients with AIDS and CMV retinitis who have been previously treated but whose retinitis either is nonresponsive or has relapsed. These three therapeutic regimens were (1) foscarnet, (2) high-dose ganciclovir, and (3) combination foscarnet and ganciclovir.

To compare two treatment strategies in patients with relapsed or nonresponsive CMV retinitis:

(1) continuing the same anti-CMV drug or (2) switching to the alternate drug.

Condition or Disease	Intervention/Treatment	Phase
HIV Infections; Acquired Immunodeficiency Syndrome; Cytomegalovirus Retinitis	Drug: Ganciclovir; Drug: Foscarnet	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. At the time of this trial, drugs approved by the United States Food and Drug Administration (FDA) for the treatment of CMV retinitis were ganciclovir (Cytovene) and foscarnet (Foscavir). Although most retinitis responds well to initial therapy with systemically administered drugs, given enough time, nearly all patients will suffer a relapse of the retinitis. Relapsed retinitis generally responds to reinduction and maintenance therapy, but the interval between successive relapses progressively shortens. The CRRT addressed the issue of the management of relapsed CMV retinitis.

The CRRT was a multicenter, randomized, controlled clinical trial comparing three regimens in patients with relapsed retinitis. Patients with AIDS and CMV retinitis that had relapsed or was nonresponsive to initial therapy were randomized to one of three regimens: (1) intravenous foscarnet reinduction at 90 mg/kg twice daily for 2 weeks, followed by maintenance therapy at 120 mg/kg/day; (2) intravenous ganciclovir reinduction at 5 mg/kg twice daily for 2 weeks followed by maintenance at 10 mg/kg/day; and (3) combination therapy, wherein patients continued their previous therapy and were reinduced with the second drug and then placed on maintenance therapy with foscarnet at 90 mg/kg/day and ganciclovir at 5 mg/kg/day.

Study Design

• Study Type: Interventional
• Actual Enrollment: 279 participants
• Allocation: Randomized
• Intervention Model: Factorial Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: Cytomegalovirus Retinitis Retreatment Trial
• Study Start Date: Dec 1, 1992
• Actual Primary Completion Date: Mar 1, 1995
• Actual Study Completion Date: Mar 1, 1995

Arms and Interventions

Arm	Intervention/Treatment
Experimental: intravenous foscarnet intravenous foscarnet reinduction at 90 mg/kg twice daily for 2 weeks, followed by maintenance therapy at 120 mg/kg/day	Drug: Foscarnet; intravenous foscarnet induction at 90 mg/kg twice daily for 2 weeks, followed by maintenance therapy at 120 mg/kg/day; Other Names: foscavir
Active Comparator: intravenous ganciclovir intravenous ganciclovir reinduction at 5 mg/kg twice daily for 2 weeks followed by maintenance at 10 mg/kg/day	Drug: Ganciclovir; intravenous ganciclovir induction at 5 mg/kg twice daily for 2 weeks followed by maintenance at 10 mg/kg/day; Other Names: cytovene
Active Comparator: combination therapy combination therapy, wherein patients continued their previous therapy and were reinduced with the second drug and then placed on maintenance therapy with foscarnet at 90 mg/kg/day and ganciclovir at 5 mg/kg/day.	Drug: Ganciclovir; intravenous ganciclovir induction at 5 mg/kg twice daily for 2 weeks followed by maintenance at 10 mg/kg/day; Other Names: cytovene ; Drug: Foscarnet; intravenous foscarnet induction at 90 mg/kg twice daily for 2 weeks, followed by maintenance therapy at 120 mg/kg/day; Other Names: foscavir

Outcome Measures

Primary Outcome Measures

1. Morbidity [Patients will be seen at baseline, monthly for six months, and then every three months until death or termination of the trial]

   To determine the best therapeutic regimen, using currently approved drugs, for treatment of relapsed cytomegalovirus (CMV) retinitis.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

inclusion criteria: Males and females eligible for the CRRT must have been age 18 years or older and have had AIDS and CMV retinitis. They must have had active CMV despite a minimum of 28 days of previous treatment with an anti-CMV drug. Furthermore, they must have had an absolute neutrophil count greater than or equal to 500 cells/µL, platelet count greater than or equal to 20,000 cells/µL, and a serum creatinine < 2.5 mg/dL in order to tolerate the drug regimens.

exclusion criteria: history of intolerance to ganciclovir or foscarnet, history of therapy involving the combination of foscarnet and ganciclovir, unwillingness to practice appropriate birth control, active drug or alcohol abuse, media opacity, retinal detachment not scheduled for surgical repair

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• Johns Hopkins Bloomberg School of Public Health
• National Eye Institute (NEI)
• National Institute of Allergy and Infectious Diseases (NIAID)
• Johns Hopkins University
• University of Wisconsin, Madison
• Baylor College of Medicine
• Tulane University School of Medicine
• Icahn School of Medicine at Mount Sinai
• New York Presbyterian Hospital
• New York University
• Northwestern University
• University of California, Los Angeles
• University of California, San Francisco
• University of California, San Diego
• University of Miami
• University of North Carolina, Chapel Hill
• Memorial Sloan Kettering Cancer Center

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• NEI Press Release-Two Drug Treatment Is Effective Against Recurrent Eye Infection In AIDS Patients

Publications

• Combination foscarnet and ganciclovir therapy vs monotherapy for the treatment of relapsed cytomegalovirus retinitis in patients with AIDS. The Cytomegalovirus Retreatment Trial. The Studies of Ocular Complications of AIDS Research Group in Collaboration with the AIDS Clinical Trials Group. Arch Ophthalmol. 1996 Jan;114(1):23-33.
• Martin BK, Kaplan Gilpin AM, Jabs DA, Wu AW; Studies of Ocular Complications of AIDS Research Group. Reliability, validity, and responsiveness of general and disease-specific quality of life measures in a clinical trial for cytomegalovirus retinitis. J Clin Epidemiol. 2001 Apr;54(4):376-86.

• Responsible Party: Curtis Meinert, Curtis Meinert, PhD, Johns Hopkins Bloomberg School of Public Health
• ClinicalTrials.gov Identifier: NCT00000134
• Other Study ID Numbers: NEI-33; U10EY008057; U01AI027668
• First Posted: Sep 24, 1999
• Last Update Posted: Sep 14, 2015
• Last Verified: Aug 1, 2015

• Additional relevant MeSH terms: HIV Infections; Acquired Immunodeficiency Syndrome; Cytomegalovirus Retinitis; Retinitis; Immunologic Deficiency Syndromes; Ganciclovir; Ganciclovir triphosphate; Foscarnet

Study Results

Participant Flow

Recruitment Details	December 1992

Arm/Group Title	Intravenous Foscarnet	Intravenous Ganciclovir	Combination Therapy
Arm/Group Description	intravenous foscarnet reinduction at 90 mg/kg twice daily for 2 weeks, followed by maintenance therapy at 120 mg/kg/day Foscarnet: intravenous foscarnet induction at 90 mg/kg twice daily for 2 weeks, followed by maintenance therapy at 120 mg/kg/day	intravenous ganciclovir reinduction at 5 mg/kg twice daily for 2 weeks followed by maintenance at 10 mg/kg/day Ganciclovir: intravenous ganciclovir induction at 5 mg/kg twice daily for 2 weeks followed by maintenance at 10 mg/kg/day	combination therapy, wherein patients continued their previous therapy and were reinduced with the second drug and then placed on maintenance therapy with foscarnet at 90 mg/kg/day and ganciclovir at 5 mg/kg/day. Ganciclovir: intravenous ganciclovir induction at 5 mg/kg twice daily for 2 weeks followed by maintenance at 10 mg/kg/day Foscarnet: intravenous foscarnet induction at 90 mg/kg twice daily for 2 weeks, followed by maintenance therapy at 120 mg/kg/day
Period Title: Overall Study
STARTED	89	94	96
COMPLETED	89	94	96
NOT COMPLETED	0	0	0

Baseline Characteristics

Arm/Group Title	Intravenous Foscarnet	Intravenous Ganciclovir	Combination Therapy	Total
Arm/Group Description	intravenous foscarnet reinduction at 90 mg/kg twice daily for 2 weeks, followed by maintenance therapy at 120 mg/kg/day Foscarnet: intravenous foscarnet induction at 90 mg/kg twice daily for 2 weeks, followed by maintenance therapy at 120 mg/kg/day	intravenous ganciclovir reinduction at 5 mg/kg twice daily for 2 weeks followed by maintenance at 10 mg/kg/day Ganciclovir: intravenous ganciclovir induction at 5 mg/kg twice daily for 2 weeks followed by maintenance at 10 mg/kg/day	combination therapy, wherein patients continued their previous therapy and were reinduced with the second drug and then placed on maintenance therapy with foscarnet at 90 mg/kg/day and ganciclovir at 5 mg/kg/day. Ganciclovir: intravenous ganciclovir induction at 5 mg/kg twice daily for 2 weeks followed by maintenance at 10 mg/kg/day Foscarnet: intravenous foscarnet induction at 90 mg/kg twice daily for 2 weeks, followed by maintenance therapy at 120 mg/kg/day	Total of all reporting groups
Overall Participants	89	94	96	279
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	89 100%	94 100%	96 100%	279 100%
>=65 years	0 0%	0 0%	0 0%	0 0%
Sex: Female, Male (Count of Participants)
Female	7 7.9%	6 6.4%	10 10.4%	23 8.2%
Male	82 92.1%	88 93.6%	86 89.6%	256 91.8%
Region of Enrollment (participants) [Number]
United States	89 100%	94 100%	96 100%	279 100%

Outcome Measures

1. Primary Outcome

Title	Morbidity
Description	To determine the best therapeutic regimen, using currently approved drugs, for treatment of relapsed cytomegalovirus (CMV) retinitis.
Time Frame	Patients will be seen at baseline, monthly for six months, and then every three months until death or termination of the trial

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Intravenous Foscarnet	Intravenous Ganciclovir	Combination Therapy
Arm/Group Description	intravenous foscarnet reinduction at 90 mg/kg twice daily for 2 weeks, followed by maintenance therapy at 120 mg/kg/day Foscarnet: intravenous foscarnet induction at 90 mg/kg twice daily for 2 weeks, followed by maintenance therapy at 120 mg/kg/day	intravenous ganciclovir reinduction at 5 mg/kg twice daily for 2 weeks followed by maintenance at 10 mg/kg/day Ganciclovir: intravenous ganciclovir induction at 5 mg/kg twice daily for 2 weeks followed by maintenance at 10 mg/kg/day	combination therapy, wherein patients continued their previous therapy and were reinduced with the second drug and then placed on maintenance therapy with foscarnet at 90 mg/kg/day and ganciclovir at 5 mg/kg/day. Ganciclovir: intravenous ganciclovir induction at 5 mg/kg twice daily for 2 weeks followed by maintenance at 10 mg/kg/day Foscarnet: intravenous foscarnet induction at 90 mg/kg twice daily for 2 weeks, followed by maintenance therapy at 120 mg/kg/day
Measure Participants	88	93	93
Number [participants]	88 98.9%	93 98.9%	93 96.9%

Adverse Events

Time Frame	1 year, 4 months
Arm/Group Title	Intravenous Foscarnet		Intravenous Ganciclovir		Combination Therapy
Arm/Group Description	intravenous foscarnet reinduction at 90 mg/kg twice daily for 2 weeks, followed by maintenance therapy at 120 mg/kg/day Foscarnet: intravenous foscarnet induction at 90 mg/kg twice daily for 2 weeks, followed by maintenance therapy at 120 mg/kg/day		intravenous ganciclovir reinduction at 5 mg/kg twice daily for 2 weeks followed by maintenance at 10 mg/kg/day Ganciclovir: intravenous ganciclovir induction at 5 mg/kg twice daily for 2 weeks followed by maintenance at 10 mg/kg/day		combination therapy, wherein patients continued their previous therapy and were reinduced with the second drug and then placed on maintenance therapy with foscarnet at 90 mg/kg/day and ganciclovir at 5 mg/kg/day. Ganciclovir: intravenous ganciclovir induction at 5 mg/kg twice daily for 2 weeks followed by maintenance at 10 mg/kg/day Foscarnet: intravenous foscarnet induction at 90 mg/kg twice daily for 2 weeks, followed by maintenance therapy at 120 mg/kg/day
All Cause Mortality
	Intravenous Foscarnet		Intravenous Ganciclovir		Combination Therapy
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Intravenous Foscarnet		Intravenous Ganciclovir		Combination Therapy
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	32/88 (36.4%)		41/93 (44.1%)		51/93 (54.8%)
Blood and lymphatic system disorders
Neutropenia	32/88 (36.4%)	86	41/93 (44.1%)	95	51/93 (54.8%)	107
Thrombocytopenia	14/88 (15.9%)	28	8/93 (8.6%)	19	15/93 (16.1%)	40
Other (Not Including Serious) Adverse Events
	Intravenous Foscarnet		Intravenous Ganciclovir		Combination Therapy
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	7/88 (8%)		7/93 (7.5%)		10/93 (10.8%)
Infections and infestations
Hospitalizations	7/88 (8%)	9	7/93 (7.5%)	10	10/93 (10.8%)	11

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.