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A Phase II Dose-Ranging, Open-Labelled Trial of Foscarnet Salvage Therapy for AIDS Patients With Sight-Threatening CMV Retinitis Who Cannot Be Treated With Ganciclovir Due To Myelosuppression or Treatment Failure

Primary Purpose

Cytomegalovirus Retinitis, HIV Infections

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Foscarnet sodium
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, Foscarnet, Cytomegalovirus Infections, Acquired Immunodeficiency Syndrome, Antiviral Agents

Eligibility Criteria

13 Years - 65 Years (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria Concurrent Medication: Allowed: Aerosolized pentamidine for Pneumocystis carinii pneumonia (PCP) prophylaxis. Oral antibiotics if patient is hematologically stable on that regimen for at least 30 days prior to study entry. Therapy with vancomycin. Drug therapy for Kaposi's sarcoma if patient is hematologically stable for at least 30 days prior to study entry. Initiate or resume zidovudine (AZT) in 2nd week of foscarnet maintenance therapy at dose of 100 or 200 mg q4h at investigator's discretion. Initiate or continue erythropoietin therapy via the treatment IND mechanism. Initiate or continue therapy with investigational triazoles for disseminated fungal infections. Caution should be used in concurrent use of foscarnet and ciprofloxacin, as such use has appeared to exacerbate renal failure in one patient. Prior Medication: Allowed: Oral antibiotics if patient is hematologically stable on that regimen for at least 30 days prior to study entry. Drug therapy for Kaposi's sarcoma if patient is hematologically stable for at least 30 days prior to study entry. Exclusion Criteria Co-existing Condition: Patients with the following are excluded: Corneal, lens, or vitreous opacification that precludes examination of the fundi. Clinically significant pulmonary or neurologic impairment, including intubation or coma. Karnofsky performance status = or < 50. Concurrent Medication: Excluded: Immunomodulators. Biologic response modifiers. Investigational agents (other than erythropoietin and investigational triazoles). Ganciclovir. Didanosine (ddI). Systemic acyclovir. CMV hyperimmune serum / globulin. Interferons. Nephrotoxic agents including aminoglycosides, amphotericin B, parenteral pentamidine. Caution should be used in the concurrent use of foscarnet and ciprofloxacin, as such use has appeared to exacerbate renal failure in one patient. Patients with the following are excluded: Corneal, lens, or vitreous opacification that precludes examination of the fundi. Clinically significant pulmonary or neurologic impairment, including intubation or coma. Unwilling or unable to suspend zidovudine treatment until 2nd week of foscarnet maintenance therapy. Prior Medication: Excluded: Foscarnet for cytomegalovirus retinitis. Systemic acyclovir. Immunomodulators. Biologic response modifiers. Investigational agents (other than erythropoietin and investigational triazoles). AIDS patients with active cytomegalovirus (CMV) retinitis who cannot be treated with ganciclovir. At least one pending CMV culture from both blood (buffy-coat) and urine must be obtained prior to study entry. Patients must be able to give informed consent. Patients with a history of a seizure disorder or central nervous system mass lesion will be included.

Sites / Locations

  • USC CRS
  • Ucsf Aids Crs
  • Univ. of Miami AIDS CRS
  • Johns Hopkins Adult AIDS CRS
  • Massachusetts General Hospital ACTG CRS
  • Washington U CRS
  • SUNY - Buffalo, Erie County Medical Ctr.
  • NY Univ. HIV/AIDS CRS
  • Cornell University A2201
  • Univ. of Rochester ACTG CRS
  • Duke Univ. Med. Ctr. Adult CRS

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

First Posted
November 2, 1999
Last Updated
October 26, 2021
Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)
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1. Study Identification

Unique Protocol Identification Number
NCT00000691
Brief Title
A Phase II Dose-Ranging, Open-Labelled Trial of Foscarnet Salvage Therapy for AIDS Patients With Sight-Threatening CMV Retinitis Who Cannot Be Treated With Ganciclovir Due To Myelosuppression or Treatment Failure
Official Title
A Phase II Dose-Ranging, Open-Labelled Trial of Foscarnet Salvage Therapy for AIDS Patients With Sight-Threatening CMV Retinitis Who Cannot Be Treated With Ganciclovir Due To Myelosuppression or Treatment Failure
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
August 1992 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)

4. Oversight

5. Study Description

Brief Summary
To examine the usefulness and safety of the antiviral drug foscarnet in treating AIDS patients with cytomegalovirus (CMV) infection that is causing sight-threatening inflammation of the retina in one or both eyes (CMV retinitis). Because of the seriousness of sight-threatening CMV retinitis in AIDS patients and a lack of other available treatments for those patients who cannot be treated with ganciclovir (DHPG) (because of its toxic effect on the body's blood-forming cells, because it did not control the disease, or because patient's blood cell or platelet counts are too low to begin with), it is worthwhile to try an immediate trial with foscarnet. AMENDED: ACTG 093 was originally designed as a randomized dose-ranging study of foscarnet maintenance therapy. Patients enrolled between March 17, 1989, and January 1, 1990, received either 60 mg/kg/day or 90/mg/kg day as maintenance therapy following the 2 week induction period. Based on the preliminary results of ACTG 015/915, which studied maintenance doses of foscarnet of 60 mg/kg/day, 90 mg/kg/day and 120 mg/kg/day, the 60-mg/kg/day and 90/mg/kg/day arms of this study have been closed. All patients entering the study beginning January 2, 1990 will receive foscarnet maintenance therapy on a 120/mg/kg/day algorithm following induction.
Detailed Description
Because of the seriousness of sight-threatening CMV retinitis in AIDS patients and a lack of other available treatments for those patients who cannot be treated with ganciclovir (DHPG) (because of its toxic effect on the body's blood-forming cells, because it did not control the disease, or because patient's blood cell or platelet counts are too low to begin with), it is worthwhile to try an immediate trial with foscarnet. AMENDED: ACTG 093 was originally designed as a randomized dose-ranging study of foscarnet maintenance therapy. Patients enrolled between March 17, 1989, and January 1, 1990, received either 60 mg/kg/day or 90/mg/kg day as maintenance therapy following the 2 week induction period. Based on the preliminary results of ACTG 015/915, which studied maintenance doses of foscarnet of 60 mg/kg/day, 90 mg/kg/day and 120 mg/kg/day, the 60-mg/kg/day and 90/mg/kg/day arms of this study have been closed. All patients entering the study beginning January 2, 1990 will receive foscarnet maintenance therapy on a 120/mg/kg/day algorithm following induction. AMENDED: The ACTG 093 optional extended maintenance therapy period will conclude on January 2, 1991 in order to facilitate timely analysis of this study. All patients who wish to continue foscarnet therapy should be referred to Astra Protocol 90-FOS-14 at telephone number 800-292-5775. Original design: Patients are placed into two groups: (1) patients who have a sight-threatening lesion in the retina of an eye with vision that can be saved (corrected vision of 20/100 or better) and who cannot be treated with DHPG, and (2) patients whose retinitis has quickly gotten worse and/or has shown resistance to DHPG treatment. Both groups will receive a beginning (induction) dose of foscarnet by vein (IV) for 2 weeks, followed by a maintenance dose for 8 weeks with an option to continue up to 24 weeks. AMENDED: Patients entering the study on or after 01/02/90 receive the standard two week course of foscarnet induction therapy and receive maintenance therapy. Treatment is given for a ten week study period or until progression occurs or toxicity endpoints are reached. If retinitis is stable and foscarnet well-tolerated, maintenance therapy may be extended for a period not to exceed 1 year.

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, Foscarnet, Cytomegalovirus Infections, Acquired Immunodeficiency Syndrome, Antiviral Agents

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Enrollment
156 (false)

8. Arms, Groups, and Interventions

Intervention Type
Drug
Intervention Name(s)
Foscarnet sodium

10. Eligibility

Sex
All
Minimum Age & Unit of Time
13 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria Concurrent Medication: Allowed: Aerosolized pentamidine for Pneumocystis carinii pneumonia (PCP) prophylaxis. Oral antibiotics if patient is hematologically stable on that regimen for at least 30 days prior to study entry. Therapy with vancomycin. Drug therapy for Kaposi's sarcoma if patient is hematologically stable for at least 30 days prior to study entry. Initiate or resume zidovudine (AZT) in 2nd week of foscarnet maintenance therapy at dose of 100 or 200 mg q4h at investigator's discretion. Initiate or continue erythropoietin therapy via the treatment IND mechanism. Initiate or continue therapy with investigational triazoles for disseminated fungal infections. Caution should be used in concurrent use of foscarnet and ciprofloxacin, as such use has appeared to exacerbate renal failure in one patient. Prior Medication: Allowed: Oral antibiotics if patient is hematologically stable on that regimen for at least 30 days prior to study entry. Drug therapy for Kaposi's sarcoma if patient is hematologically stable for at least 30 days prior to study entry. Exclusion Criteria Co-existing Condition: Patients with the following are excluded: Corneal, lens, or vitreous opacification that precludes examination of the fundi. Clinically significant pulmonary or neurologic impairment, including intubation or coma. Karnofsky performance status = or < 50. Concurrent Medication: Excluded: Immunomodulators. Biologic response modifiers. Investigational agents (other than erythropoietin and investigational triazoles). Ganciclovir. Didanosine (ddI). Systemic acyclovir. CMV hyperimmune serum / globulin. Interferons. Nephrotoxic agents including aminoglycosides, amphotericin B, parenteral pentamidine. Caution should be used in the concurrent use of foscarnet and ciprofloxacin, as such use has appeared to exacerbate renal failure in one patient. Patients with the following are excluded: Corneal, lens, or vitreous opacification that precludes examination of the fundi. Clinically significant pulmonary or neurologic impairment, including intubation or coma. Unwilling or unable to suspend zidovudine treatment until 2nd week of foscarnet maintenance therapy. Prior Medication: Excluded: Foscarnet for cytomegalovirus retinitis. Systemic acyclovir. Immunomodulators. Biologic response modifiers. Investigational agents (other than erythropoietin and investigational triazoles). AIDS patients with active cytomegalovirus (CMV) retinitis who cannot be treated with ganciclovir. At least one pending CMV culture from both blood (buffy-coat) and urine must be obtained prior to study entry. Patients must be able to give informed consent. Patients with a history of a seizure disorder or central nervous system mass lesion will be included.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
MA Jacobson
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
C Crumpacker
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
ZIP/Postal Code
94114
Country
United States
Facility Name
Univ. of Miami AIDS CRS
City
Miami
State/Province
Florida
ZIP/Postal Code
33136
Country
United States
Facility Name
Johns Hopkins Adult AIDS CRS
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21287
Country
United States
Facility Name
Massachusetts General Hospital ACTG CRS
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
Facility Name
Washington U CRS
City
Saint Louis
State/Province
Missouri
Country
United States
Facility Name
SUNY - Buffalo, Erie County Medical Ctr.
City
Buffalo
State/Province
New York
ZIP/Postal Code
14215
Country
United States
Facility Name
NY Univ. HIV/AIDS CRS
City
New York
State/Province
New York
ZIP/Postal Code
10016
Country
United States
Facility Name
Cornell University A2201
City
New York
State/Province
New York
ZIP/Postal Code
10021
Country
United States
Facility Name
Univ. of Rochester ACTG CRS
City
Rochester
State/Province
New York
ZIP/Postal Code
14642
Country
United States
Facility Name
Duke Univ. Med. Ctr. Adult CRS
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27710
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
1663770
Citation
Harb GE, Bacchetti P, Jacobson MA. Survival of patients with AIDS and cytomegalovirus disease treated with ganciclovir or foscarnet. AIDS. 1991 Aug;5(8):959-65. doi: 10.1097/00002030-199108000-00006.
Results Reference
background
PubMed Identifier
1645385
Citation
Jacobson MA, Drew WL, Feinberg J, O'Donnell JJ, Whitmore PV, Miner RD, Parenti D. Foscarnet therapy for ganciclovir-resistant cytomegalovirus retinitis in patients with AIDS. J Infect Dis. 1991 Jun;163(6):1348-51. doi: 10.1093/infdis/163.6.1348.
Results Reference
background
PubMed Identifier
1827127
Citation
Jacobson MA, Gambertoglio JG, Aweeka FT, Causey DM, Portale AA. Foscarnet-induced hypocalcemia and effects of foscarnet on calcium metabolism. J Clin Endocrinol Metab. 1991 May;72(5):1130-5. doi: 10.1210/jcem-72-5-1130.
Results Reference
background
PubMed Identifier
8011248
Citation
Jacobson MA, Wulfsohn M, Feinberg JE, Davis R, Power M, Owens S, Causey D, Heath-Chiozzi ME, Murphy RL, Cheung TW, et al. Phase II dose-ranging trial of foscarnet salvage therapy for cytomegalovirus retinitis in AIDS patients intolerant of or resistant to ganciclovir (ACTG protocol 093). AIDS Clinical Trials Group of the National Institute of Allergy and Infectious Diseases. AIDS. 1994 Apr;8(4):451-9. doi: 10.1097/00002030-199404000-00006.
Results Reference
background
PubMed Identifier
1323624
Citation
Reddy MM, Grieco MH, McKinley GF, Causey DM, van der Horst CM, Parenti DM, Hooton TM, Davis RB, Jacobson MA. Effect of foscarnet therapy on human immunodeficiency virus p24 antigen levels in AIDS patients with cytomegalovirus retinitis. J Infect Dis. 1992 Sep;166(3):607-10. doi: 10.1093/infdis/166.3.607.
Results Reference
background
PubMed Identifier
2160217
Citation
Farese RV Jr, Schambelan M, Hollander H, Stringari S, Jacobson MA. Nephrogenic diabetes insipidus associated with foscarnet treatment of cytomegalovirus retinitis. Ann Intern Med. 1990 Jun 15;112(12):955-6. doi: 10.7326/0003-4819-112-12-955. No abstract available.
Results Reference
background

Learn more about this trial

A Phase II Dose-Ranging, Open-Labelled Trial of Foscarnet Salvage Therapy for AIDS Patients With Sight-Threatening CMV Retinitis Who Cannot Be Treated With Ganciclovir Due To Myelosuppression or Treatment Failure

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