A Phase I/II Pilot Treatment Study Of CSF Penetration And Response To Ganciclovir And Foscarnet In CMV Neurologic Disease.

October 27, 2021 updated by: National Institute of Allergy and Infectious Diseases (NIAID)

To determine the safety and CSF penetration of combined ganciclovir and foscarnet treatment for presumed cytomegalovirus encephalitis or radiculomyelopathy.

This study proposes to investigate the use of combined ganciclovir and foscarnet to maximize the antiviral regimen. Current evidence suggests that a combination of ganciclovir and foscarnet may be the most efficacious therapy and appears to be well tolerated. This study will provide key information regarding safety and CSF penetration of the drugs available for treatment of these lethal diseases. It will also provide preliminary information regarding virologic factors relevant to CMV CNS disease. The study will also provide further data about the natural history of CMV brain infection detected by a combination of symptom complex and PCR identification of CMV in CSF and the potential of semi-quantitative PCR evaluation of the CSF for the disease.

Study Overview

Status

Withdrawn

Conditions

Intervention / Treatment

Detailed Description

This study proposes to investigate the use of combined ganciclovir and foscarnet to maximize the antiviral regimen. Current evidence suggests that a combination of ganciclovir and foscarnet may be the most efficacious therapy and appears to be well tolerated. This study will provide key information regarding safety and CSF penetration of the drugs available for treatment of these lethal diseases. It will also provide preliminary information regarding virologic factors relevant to CMV CNS disease. The study will also provide further data about the natural history of CMV brain infection detected by a combination of symptom complex and PCR identification of CMV in CSF and the potential of semi-quantitative PCR evaluation of the CSF for the disease.

Patients will be stratified by clinical syndrome as having either primarily A) encephalitis; or B) radiculomyelitis. If patient has combined encephalitis and radiculomyelitis, then the patient will be stratified as encephalitis. CMV therapy with ganciclovir and foscarnet will first be given at an induction level and then a maintenance level. For the first 4 weeks, patients will be given foscarnet plus ganciclovir. Then for the following 20 weeks, patients will be given foscarnet plus ganciclovir with ganciclovir at a lower dose. NOTE: A maximum of 10 patients that have proven to be intolerant to either foscarnet or ganciclovir may receive the alternate agent alone.

NOTE: Ganciclovir experienced subjects will be given GCV at induction and maintenance doses if tolerated.

NOTE: Induction doses will not be re-started in the face of clinical relapse on switching to maintenance therapy.

Study Type

Interventional

Phase

  • Phase 1

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

13 years and older (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria

Concurrent Medication:

Allowed:

Patients with treated, stable toxoplasmosis encephalitis with documented stable CT or MR scans may be enrolled if maintenance suppressive therapy is continued.

Patients must have:

  • Documented HIV infection.
  • Encephalopathy or radiculomyelitis.
  • CSF positive for CMV by PCR.
  • Signed informed consent from a parent or legal guardian for patients < 18 years.
  • CSF cytological analysis should be obtained at the time of enrollment or within 2 weeks prior to enrollment.

NOTE:

  • Co-enrollment is encouraged where study procedures do not conflict. Protocols investigating antiviral regimens with potential activity against CMV or other human herpes viruses will be ineligible.

Exclusion Criteria

Co-existing Condition:

Patients with the following symptoms and conditions are excluded:

  • Active CNS infection or malignancy, other than due to CMV or HIV.
  • A positive CSF VDRL.
  • Any evidence of active disease such as a substantial increase in cryptococcal antigen titer or positive culture. However, patients may be enrolled with stable, treated cryptococcal meningitis.
  • A dermatomal or disseminated varicella-zoster infection within 30 days prior to enrollment.
  • An active, symptomatic systemic infection, other tan HIV or CMV, for which the patient is not receiving stable therapy for at least 30 days.
  • Any other advanced disease likely to cause death in <6 months.
  • Known intolerance to both foscarnet and ganciclovir.
  • Inability to safely perform a lumbar puncture.

Concurrent Medication:

Excluded:

  • Patients on prophylactic antiviral therapy at the time of study enrollment will not be allowed to continue this medication during the study. In the event of the appearance of HSV or VZV infections after enrollment in the study that require systemic therapy, acyclovir or other appropriate medication may be instituted.
  • Patients may not receive ZDV therapy during the initial 4 weeks of the study. Concurrent ZDV therapy will be started during maintenance therapy if tolerated. Bone marrow sparing antiretroviral therapy may be used at the investigator's discretion.

NOTE:

  • Concurrent medications should be kept to a minimum because of possible interference with the assessment of both safety and pharmacokinetics. But medications absolutely necessary for the subject's welfare may be administered at the discretion of the investigator.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Interventional Model: Parallel Assignment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

National Institute of Allergy and Infectious Diseases (NIAID)

Investigators

  • Study Chair: Clifford D
  • Study Chair: Tselis A

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

First Submitted

November 2, 1999

First Submitted That Met QC Criteria

August 30, 2001

First Posted (Estimate)

August 31, 2001

Study Record Updates

Last Update Posted (Actual)

October 29, 2021

Last Update Submitted That Met QC Criteria

October 27, 2021

Last Verified

October 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ACTG 305
  • 11280 (Registry Identifier: DAIDS ES Registry Number)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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