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

HIV Infections Clinical Trial

— CRRT  

Official title:

Cytomegalovirus Retinitis Retreatment Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00000134
• Other study ID #: NEI-33
• Secondary ID: U10EY008057U01AI
• Status: Completed
• Phase: Phase 3
• First received: September 23, 1999
• Last updated: August 11, 2015
• Start date: December 1992
• Est. completion date: March 1995

Study information

• Verified date: August 2015
• Source: Johns Hopkins Bloomberg School of Public Health
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 279
• Est. completion date: March 1995
• Est. primary completion date: March 1995
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Factorial Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Acquired Immunodeficiency Syndrome
• Cytomegalovirus Retinitis
• HIV Infections
• Immunologic Deficiency Syndromes
• Retinitis

Intervention

Drug:
• 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

Locations

Country	Name	City	State
n/a

Sponsors (17)

Lead Sponsor

Collaborator

Johns Hopkins Bloomberg School of Public Health

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

References & Publications (2)

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. — View Citation

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. — View Citation

Outcome

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

External Links

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