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A Study of Foscarnet Plus Ganciclovir in the Treatment of Cytomegalovirus of the Eye in Patients With AIDS Who Have Already Been Treated With Ganciclovir

Primary Purpose

Cytomegalovirus Retinitis, HIV Infections

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Foscarnet sodium
Ganciclovir
Sponsored by
National Institute of Allergy and Infectious Diseases (NIAID)
About
Eligibility
Locations
Outcomes
Full info

About this trial

This is an interventional treatment trial for Cytomegalovirus Retinitis focused on measuring Retinitis, AIDS-Related Opportunistic Infections, Ganciclovir, Drug Evaluation, Drug Therapy, Combination, Foscarnet, Cytomegalovirus Infections, Acquired Immunodeficiency Syndrome

Eligibility Criteria

13 Years - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria Concurrent Medication: Allowed: Chemotherapy for Kaposi's sarcoma (excluding interferon) if patient is hematologically stable for at least 30 days prior to entry. Zidovudine (AZT), dideoxyinosine (ddI), dideoxycytidine (ddC) after first two weeks of study period if absolute neutrophil count is > 1000 cells/mm3 and hemoglobin = or > 8 g/dl. Vancomycin. Fluconazole or investigational triazoles (e.g., itraconazole, SCH 39304) for disseminated fungal infection. Pneumocystis carinii pneumonia prophylaxis (except parenteral pentamidine). Acyclovir or other appropriate medication may be instituted in the event of the appearance of Herpes simplex virus (HSV) or Varicella zoster virus (VZV) infections. G-CSF or GM-CSF for grade 4 neutropenia. Concurrent Treatment: Allowed: Recombinant human erythropoietin. Prior Medication: Required: Completion of 14-day course of intravenous ganciclovir induction therapy (2.5 mg/kg IV q8h or 5 mg/kg q12h for 14 days) or foscarnet induction therapy (60 mg/kg q8h adjusted for renal function for 14 days) within 1 week prior to study entry. Patients who do not initiate the study immediately upon completing ganciclovir induction therapy should receive a maintenance ganciclovir regimen of 5 mg/kg/day or 6 mg/kg/day 5 x week or a foscarnet regimen of 90-120 mg/kg/day until initiating study drug. Patients must: Have a diagnosis of cytomegalovirus retinitis and HIV infection. Be capable of giving informed consent. Patients < 18 years of age may participate with the consent of parent, guardian, or person with power of attorney. Allowed: History of seizure disorder or a central nervous system (CNS) mass lesion. Exclusion Criteria Co-existing Condition: Patients with the following conditions or symptoms are excluded: Evidence of tuberculous, diabetic or hypertensive retinopathy. Osteomalacia, neoplasm metastatic to bone or other bone disease. Any clinically significant pulmonary or neurologic impairment (for example, patients who are intubated or comatose). Retinal detachment. Corneal, lens, or vitreous opacification precluding funduscopic exam. Concurrent Medication: Excluded: Immunomodulators, biologic response modifiers or investigational agents not specifically allowed. Aminoglycosides, amphotericin B, probenecid, parenteral pentamidine. Zidovudine (AZT), dideoxyinosine (ddI), dideoxycytidine (ddC) until completion of second week of maintenance therapy. ddC use is discouraged but not prohibited because of paucity of experience of this drug with ganciclovir and foscarnet. Anti-cytomegalovirus (CMV) therapy: Ganciclovir, CMV hyperimmune serum/globulin, interferons, immunomodulators. Prophylactic antiviral therapy with acyclovir. Patients with the following are excluded: Active AIDS-defining opportunistic infection requiring therapy that is currently causing nephrotoxicity or myelosuppression. Known hypersensitivity to either of the study therapies. Prior Medication: Excluded: Foscarnet or ganciclovir for CMV retinitis (excluding the 14-day induction period). Prior Treatment: Excluded: Cytomegalovirus (CMV) hyperimmune globulin within 14 days prior to study entry.

Sites / Locations

  • USC CRS
  • Ucsf Aids Crs
  • Washington U CRS
  • Memorial Sloan-Kettering Cancer Ctr.
  • Unc Aids Crs
  • University of Washington AIDS CRS

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

First Posted
November 2, 1999
Last Updated
October 28, 2021
Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)
Collaborators
Astra USA, Hoffmann-La Roche
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1. Study Identification

Unique Protocol Identification Number
NCT00000970
Brief Title
A Study of Foscarnet Plus Ganciclovir in the Treatment of Cytomegalovirus of the Eye in Patients With AIDS Who Have Already Been Treated With Ganciclovir
Official Title
A Phase I Open-Labeled Study of Long Term Combined or Alternating Foscarnet/Ganciclovir Maintenance Therapy for AIDS Patients With CMV Retinitis After Ganciclovir Induction Therapy
Study Type
Interventional

2. Study Status

Record Verification Date
October 2021
Overall Recruitment Status
Completed
Study Start Date
undefined (undefined)
Primary Completion Date
undefined (undefined)
Study Completion Date
June 1993 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)
Collaborators
Astra USA, Hoffmann-La Roche

4. Oversight

5. Study Description

Brief Summary
To examine the safety and tolerance of the administration of ganciclovir and foscarnet given together or alternately; to determine the interactive pharmacokinetics (blood level) profile of long-term combined and alternating therapy with these two drugs. Additional objectives are to examine the effect of these treatments in controlling time to cytomegalovirus (CMV) retinitis progression and to examine the antiviral activity of combined and alternating ganciclovir/foscarnet treatment and development of antiviral resistance. Sight-threatening CMV retinitis occurs in at least 6 percent of AIDS patients. By 1991 (US), there may be 6000 to 10000 patients with CMV retinitis. Many clinical reports suggest that both ganciclovir (DHPG) and foscarnet have an antiviral effect against CMV that is often associated with clinical stabilization. Effectiveness of ganciclovir and foscarnet is correlated with weekly maintenance and since toxicity is dose-limiting in up to 20 percent of patients receiving either drug for long periods, it may be beneficial in long-term maintenance treatment to combine or alternate these two drugs at a lower total weekly dose of each drug. This strategy may result in a greater net antiviral effect with less toxicity than is seen with either drug alone, because the toxicities of each drug are quite different.
Detailed Description
Sight-threatening CMV retinitis occurs in at least 6 percent of AIDS patients. By 1991 (US), there may be 6000 to 10000 patients with CMV retinitis. Many clinical reports suggest that both ganciclovir (DHPG) and foscarnet have an antiviral effect against CMV that is often associated with clinical stabilization. Effectiveness of ganciclovir and foscarnet is correlated with weekly maintenance and since toxicity is dose-limiting in up to 20 percent of patients receiving either drug for long periods, it may be beneficial in long-term maintenance treatment to combine or alternate these two drugs at a lower total weekly dose of each drug. This strategy may result in a greater net antiviral effect with less toxicity than is seen with either drug alone, because the toxicities of each drug are quite different. All patients have newly diagnosed CMV retinitis and have completed a 14-day course of intravenous ganciclovir or foscarnet induction therapy within 1 week prior to study entry. The maintenance period consists of a 12-week study period followed by a 40 week follow-up period. Treatment consists of either combined sequential daily maintenance therapy of both foscarnet and ganciclovir or alternating daily treatment with ganciclovir one day and foscarnet the following day.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Cytomegalovirus Retinitis, HIV Infections
Keywords
Retinitis, AIDS-Related Opportunistic Infections, Ganciclovir, Drug Evaluation, Drug Therapy, Combination, Foscarnet, Cytomegalovirus Infections, Acquired Immunodeficiency Syndrome

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Enrollment
30 (false)

8. Arms, Groups, and Interventions

Intervention Type
Drug
Intervention Name(s)
Foscarnet sodium
Intervention Type
Drug
Intervention Name(s)
Ganciclovir

10. Eligibility

Sex
All
Minimum Age & Unit of Time
13 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria Concurrent Medication: Allowed: Chemotherapy for Kaposi's sarcoma (excluding interferon) if patient is hematologically stable for at least 30 days prior to entry. Zidovudine (AZT), dideoxyinosine (ddI), dideoxycytidine (ddC) after first two weeks of study period if absolute neutrophil count is > 1000 cells/mm3 and hemoglobin = or > 8 g/dl. Vancomycin. Fluconazole or investigational triazoles (e.g., itraconazole, SCH 39304) for disseminated fungal infection. Pneumocystis carinii pneumonia prophylaxis (except parenteral pentamidine). Acyclovir or other appropriate medication may be instituted in the event of the appearance of Herpes simplex virus (HSV) or Varicella zoster virus (VZV) infections. G-CSF or GM-CSF for grade 4 neutropenia. Concurrent Treatment: Allowed: Recombinant human erythropoietin. Prior Medication: Required: Completion of 14-day course of intravenous ganciclovir induction therapy (2.5 mg/kg IV q8h or 5 mg/kg q12h for 14 days) or foscarnet induction therapy (60 mg/kg q8h adjusted for renal function for 14 days) within 1 week prior to study entry. Patients who do not initiate the study immediately upon completing ganciclovir induction therapy should receive a maintenance ganciclovir regimen of 5 mg/kg/day or 6 mg/kg/day 5 x week or a foscarnet regimen of 90-120 mg/kg/day until initiating study drug. Patients must: Have a diagnosis of cytomegalovirus retinitis and HIV infection. Be capable of giving informed consent. Patients < 18 years of age may participate with the consent of parent, guardian, or person with power of attorney. Allowed: History of seizure disorder or a central nervous system (CNS) mass lesion. Exclusion Criteria Co-existing Condition: Patients with the following conditions or symptoms are excluded: Evidence of tuberculous, diabetic or hypertensive retinopathy. Osteomalacia, neoplasm metastatic to bone or other bone disease. Any clinically significant pulmonary or neurologic impairment (for example, patients who are intubated or comatose). Retinal detachment. Corneal, lens, or vitreous opacification precluding funduscopic exam. Concurrent Medication: Excluded: Immunomodulators, biologic response modifiers or investigational agents not specifically allowed. Aminoglycosides, amphotericin B, probenecid, parenteral pentamidine. Zidovudine (AZT), dideoxyinosine (ddI), dideoxycytidine (ddC) until completion of second week of maintenance therapy. ddC use is discouraged but not prohibited because of paucity of experience of this drug with ganciclovir and foscarnet. Anti-cytomegalovirus (CMV) therapy: Ganciclovir, CMV hyperimmune serum/globulin, interferons, immunomodulators. Prophylactic antiviral therapy with acyclovir. Patients with the following are excluded: Active AIDS-defining opportunistic infection requiring therapy that is currently causing nephrotoxicity or myelosuppression. Known hypersensitivity to either of the study therapies. Prior Medication: Excluded: Foscarnet or ganciclovir for CMV retinitis (excluding the 14-day induction period). Prior Treatment: Excluded: Cytomegalovirus (CMV) hyperimmune globulin within 14 days prior to study entry.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jacobson MA
Official's Role
Study Chair
Facility Information:
Facility Name
USC CRS
City
Los Angeles
State/Province
California
ZIP/Postal Code
90033
Country
United States
Facility Name
Ucsf Aids Crs
City
San Francisco
State/Province
California
Country
United States
Facility Name
Washington U CRS
City
Saint Louis
State/Province
Missouri
Country
United States
Facility Name
Memorial Sloan-Kettering Cancer Ctr.
City
New York
State/Province
New York
ZIP/Postal Code
10021
Country
United States
Facility Name
Unc Aids Crs
City
Chapel Hill
State/Province
North Carolina
ZIP/Postal Code
27599
Country
United States
Facility Name
University of Washington AIDS CRS
City
Seattle
State/Province
Washington
ZIP/Postal Code
98122
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
8014496
Citation
Jacobson MA, Kramer F, Bassiakos Y, Hooton T, Polsky B, Geheb H, O'Donnell JJ, Walker JD, Korvick JA, van der Horst C. Randomized phase I trial of two different combination foscarnet and ganciclovir chronic maintenance therapy regimens for AIDS patients with cytomegalovirus retinitis: AIDS clinical Trials Group Protocol 151. J Infect Dis. 1994 Jul;170(1):189-93. doi: 10.1093/infdis/170.1.189.
Results Reference
background
PubMed Identifier
7712668
Citation
Aweeka FT, Gambertoglio JG, Kramer F, van der Horst C, Polsky B, Jayewardene A, Lizak P, Emrick L, Tong W, Jacobson MA. Foscarnet and ganciclovir pharmacokinetics during concomitant or alternating maintenance therapy for AIDS-related cytomegalovirus retinitis. Clin Pharmacol Ther. 1995 Apr;57(4):403-12. doi: 10.1016/0009-9236(95)90209-0.
Results Reference
background

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A Study of Foscarnet Plus Ganciclovir in the Treatment of Cytomegalovirus of the Eye in Patients With AIDS Who Have Already Been Treated With Ganciclovir

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