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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
This study has been completed.
Sponsored by: National Institute of Allergy and Infectious Diseases (NIAID)
Information provided by: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT00000691
  Purpose

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.


Condition Intervention Phase
Cytomegalovirus Retinitis
HIV Infections
Drug: Foscarnet sodium
Phase II

MedlinePlus related topics: AIDS Cytomegalovirus Infections
Drug Information available for: Ganciclovir Ganciclovir sodium Foscarnet Foscarnet sodium Fosfonet sodium Phosphonoacetic acid
U.S. FDA Resources
Study Type: Interventional
Study Design: Treatment, Dose Comparison
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

Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Estimated Enrollment: 156
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.

  Eligibility

Ages Eligible for Study:   13 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.

  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00000691

  Show 30 Study Locations
Sponsors and Collaborators
Investigators
Study Chair: MA Jacobson
Study Chair: C Crumpacker
  More Information

Publications:
Study ID Numbers: ACTG 093
Study First Received: November 2, 1999
Last Updated: June 23, 2005
ClinicalTrials.gov Identifier: NCT00000691  
Health Authority: United States: Federal Government

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
Retinitis
AIDS-Related Opportunistic Infections
Ganciclovir
Drug Evaluation
Foscarnet
Cytomegalovirus Infections
Acquired Immunodeficiency Syndrome
Antiviral Agents

Study placed in the following topic categories:
Opportunistic Infections
Phosphonoacetic Acid
Sexually Transmitted Diseases, Viral
Eye Diseases
Eye Infections
Acquired Immunodeficiency Syndrome
Cytomegalovirus Retinitis
Retinitis
Ganciclovir
Cytomegalovirus
Immunologic Deficiency Syndromes
Herpesviridae Infections
Cytomegalovirus retinitis
Virus Diseases
HIV Infections
AIDS-Related Opportunistic Infections
Sexually Transmitted Diseases
Cytomegalovirus Infections
DNA Virus Infections
Foscarnet
Cytomegalic inclusion disease
Retroviridae Infections
Retinal Diseases

Additional relevant MeSH terms:
Anti-Infective Agents
RNA Virus Infections
Slow Virus Diseases
Molecular Mechanisms of Pharmacological Action
Immune System Diseases
Eye Infections, Viral
Enzyme Inhibitors
Infection
Antiviral Agents
Pharmacologic Actions
Reverse Transcriptase Inhibitors
Anti-Retroviral Agents
Therapeutic Uses
Lentivirus Infections
Nucleic Acid Synthesis Inhibitors

ClinicalTrials.gov processed this record on January 15, 2009