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

This study has been completed.
Sponsor:
Collaborators:
Johns Hopkins University
University of Wisconsin, Madison
Baylor College of Medicine
Tulane University School of Medicine
Mount Sinai School of Medicine
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
ClinicalTrials.gov Identifier:
NCT00000134
First received: September 23, 1999
Last updated: April 10, 2015
Last verified: April 2015
  Purpose

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 Intervention Phase
HIV Infections
Acquired Immunodeficiency Syndrome
Cytomegalovirus Retinitis
Drug: Ganciclovir
Drug: Foscarnet
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Factorial Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: Cytomegalovirus Retinitis Retreatment Trial

Resource links provided by NLM:


Further study details as provided by Johns Hopkins Bloomberg School of Public Health:

Primary Outcome Measures:
  • Compare the safety and efficacy of three therapeutic regimens in patients with AIDS related CMV retinitis previously treated with foscarnet or ganciclovir whose retinitis progresses or recurs [ Time Frame: Patients will be seen at baseline, monthly for six months, and then every three months until death or termination of the trial ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Compare the safety and efficacy of continuing to treat patients with the same anti-CMV drug versus switching to the alternative drug [ Time Frame: Patients will be seen at baseline, monthly for six months, and then every three months until death or termination of the trial ] [ Designated as safety issue: Yes ]

Enrollment: 279
Study Start Date: December 1992
Study Completion Date: March 1995
Primary Completion Date: March 1995 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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. Outcome measures in this trial were survival, retinitis progression, loss of visual function (acuity and field), and morbidity.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

No Contacts or Locations Provided
  More Information

Additional Information:
Publications:
Responsible Party: Curtis Meinert, Curtis Meinert, PhD, Johns Hopkins Bloomberg School of Public Health
ClinicalTrials.gov Identifier: NCT00000134     History of Changes
Other Study ID Numbers: NEI-33, U10EY008057, U01AI027668
Study First Received: September 23, 1999
Last Updated: April 10, 2015
Health Authority: United States: Federal Government

Additional relevant MeSH terms:
Acquired Immunodeficiency Syndrome
Cytomegalovirus Retinitis
HIV Infections
Immunologic Deficiency Syndromes
Retinitis
Cytomegalovirus Infections
DNA Virus Infections
Eye Diseases
Eye Infections
Eye Infections, Viral
Herpesviridae Infections
Immune System Diseases
Lentivirus Infections
RNA Virus Infections
Retinal Diseases
Retroviridae Infections
Sexually Transmitted Diseases
Sexually Transmitted Diseases, Viral
Slow Virus Diseases
Virus Diseases
Foscarnet
Ganciclovir
Phosphonoacetic Acid
Anti-Infective Agents
Anti-Retroviral Agents
Antiviral Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Nucleic Acid Synthesis Inhibitors
Pharmacologic Actions

ClinicalTrials.gov processed this record on May 26, 2015