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

• ClinicalTrials.gov Identifier: NCT00000134
• Recruitment Status: Completed
• First Posted: September 24, 1999
• Results First Posted: September 14, 2015
• Last Update Posted: September 14, 2015
• Sponsor: Johns Hopkins Bloomberg School of Public Health
• Collaborators: 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
• Information provided by (Responsible Party): Curtis Meinert, Johns Hopkins Bloomberg School of Public Health

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 (Clinical Trial)
• 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: December 1992
• Actual Primary Completion Date: March 1995
• Actual Study Completion Date: March 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 Name: 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 Name: 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 Name: 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 Name: foscavir

Outcome Measures

Primary Outcome Measures :

1. Morbidity [ Time Frame: 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

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

No Contacts or Locations 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. doi: 10.1001/archopht.1996.01100130021004.

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.

• 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 ( U.S. NIH Grant/Contract ); U01AI027668 ( U.S. NIH Grant/Contract )
• First Posted: September 24, 1999
• Results First Posted: September 14, 2015
• Last Update Posted: September 14, 2015
• Last Verified: August 2015

Additional relevant MeSH terms:

HIV Infections; Acquired Immunodeficiency Syndrome; Cytomegalovirus Retinitis; Retinitis; Immunologic Deficiency Syndromes; Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Immune System Diseases; Slow Virus Diseases; Retinal Diseases; Eye Diseases; Eye Infections, Viral; Eye Infections; Cytomegalovirus Infections; Herpesviridae Infections; DNA Virus Infections; Ganciclovir; Ganciclovir triphosphate; Foscarnet; Antiviral Agents; Anti-Infective Agents; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors