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

NCT ID: NCT00000134

Last Updated: 2015-09-14

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 279 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 1992-12-31
• Study Completion Date: 1995-03-31

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.

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.

Conditions

HIV Infections; Acquired Immunodeficiency Syndrome; Cytomegalovirus Retinitis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: FACTORIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

intravenous foscarnet

intravenous foscarnet reinduction at 90 mg/kg twice daily for 2 weeks, followed by maintenance therapy at 120 mg/kg/day

Group Type: EXPERIMENTAL

Foscarnet

Intervention Type: DRUG

intravenous foscarnet induction at 90 mg/kg twice daily for 2 weeks, followed by maintenance therapy at 120 mg/kg/day

intravenous ganciclovir

intravenous ganciclovir reinduction at 5 mg/kg twice daily for 2 weeks followed by maintenance at 10 mg/kg/day

Group Type: ACTIVE_COMPARATOR

Ganciclovir

Intervention Type: DRUG

intravenous ganciclovir induction at 5 mg/kg twice daily for 2 weeks followed by maintenance at 10 mg/kg/day

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.

Group Type: ACTIVE_COMPARATOR

Ganciclovir

Intervention Type: DRUG

intravenous ganciclovir induction at 5 mg/kg twice daily for 2 weeks followed by maintenance at 10 mg/kg/day

Foscarnet

Intervention Type: DRUG

intravenous foscarnet induction at 90 mg/kg twice daily for 2 weeks, followed by maintenance therapy at 120 mg/kg/day

Interventions

Ganciclovir

intravenous ganciclovir induction at 5 mg/kg twice daily for 2 weeks followed by maintenance at 10 mg/kg/day

Intervention Type: DRUG

Foscarnet

intravenous foscarnet induction at 90 mg/kg twice daily for 2 weeks, followed by maintenance therapy at 120 mg/kg/day

Intervention Type: DRUG

Other Intervention Names

cytovene; foscavir

Eligibility Criteria

Inclusion Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Eye Institute (NEI)

NIH

Sponsor Role: collaborator

National Institute of Allergy and Infectious Diseases (NIAID)

NIH

Sponsor Role: collaborator

Johns Hopkins University

OTHER

Sponsor Role: collaborator

University of Wisconsin, Madison

OTHER

Sponsor Role: collaborator

Baylor College of Medicine

OTHER

Sponsor Role: collaborator

Tulane University School of Medicine

OTHER

Sponsor Role: collaborator

Icahn School of Medicine at Mount Sinai

OTHER

Sponsor Role: collaborator

New York Presbyterian Hospital

OTHER

Sponsor Role: collaborator

New York University

OTHER

Sponsor Role: collaborator

Northwestern University

OTHER

Sponsor Role: collaborator

University of California, Los Angeles

OTHER

Sponsor Role: collaborator

University of California, San Francisco

OTHER

Sponsor Role: collaborator

University of California, San Diego

OTHER

Sponsor Role: collaborator

University of Miami

OTHER

Sponsor Role: collaborator

University of North Carolina, Chapel Hill

OTHER

Sponsor Role: collaborator

Memorial Sloan Kettering Cancer Center

OTHER

Sponsor Role: collaborator

Johns Hopkins Bloomberg School of Public Health

OTHER

Sponsor Role: lead

Responsible Party

Curtis Meinert

Curtis Meinert, PhD

Responsibility Role: PRINCIPAL_INVESTIGATOR

References

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. doi: 10.1001/archopht.1996.01100130021004.

Reference Type: BACKGROUND

PMID: 8540847 (View on PubMed)

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. doi: 10.1016/s0895-4356(00)00294-8.

Reference Type: BACKGROUND

PMID: 11305288 (View on PubMed)

Other Identifiers

U10EY008057

Identifier Type: NIH

Identifier Source: secondary_id

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U01AI027668

Identifier Type: NIH

Identifier Source: secondary_id

View Link

NEI-33

Identifier Type: -

Identifier Source: org_study_id