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Long Term Treatment of Herpes Simplex Encephalitis (HSE) With Valacyclovir

Information source: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Encephalitis

Intervention: Valacyclovir (Drug); Placebo (Drug)

Phase: Phase 3

Status: Completed

Sponsored by: National Institute of Allergy and Infectious Diseases (NIAID)

Summary

This study involves patients 12 years and older who have been diagnosed with herpes simplex encephalitis (HSE) by a specific laboratory test and have completed treatment or are being treated with intravenous (given through a needle inserted into a vein) acyclovir. The purpose of the study is to determine if treatment with 4 tablets, 500 milligrams each, of valacyclovir given 3 times daily by mouth for 90 days is both effective and safe after completing intravenous acyclovir treatment and if it can increase survival with or without mild impairment of the brain and mental functions. Participants will be assigned to either drug or placebo (inactive substance) randomly (by chance). Study procedures will include blood samples and lumbar punctures (procedure in which a needle is inserted into the lower back to collect cerebral spinal fluid). Subjects will participate for up to 24 months.

Clinical Details

Official title: A Phase III Double-Blind, Placebo-Controlled Trial of Long Term Therapy of Herpes Simplex Encephalitis (HSE): An Evaluation of Valacyclovir (CASG-204)

Study design: Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Primary outcome: Survival With no or Mild Neuropsychological Impairment at 12 Months After Initiation of Study Medication as Measured by the Mattis Dementia Rating Scale (MDRS)

Secondary outcome:

Effect of Study Medication on Quality of Life Measurements.

Effect of Antiviral Therapy on Herpes Simplex Virus (HSV) Deoxyribonucleic Acid (DNA) in Cerebral Spinal Fluid (CSF)

Median Number of Reported AEs Describing Safety and Tolerance of Valacyclovir (VACV), Evaluated by the Number Adverse Events, Administered at a Dose of 2.0 Grams Given Orally 3 Times a Day for 90 Days.

Survival With no or Mild Neuropsychological Impairment at 90 Days and at 6 and 12 Months, as Measured by the Mattis Dementia Rating Scale (MDRS)

Survival With no or Mild Neuropsychological Impairment at 90 Days, and at 6 and 12 Months, as Measured by the Mini-Mental Status Examination (MMSE).

Survival With no or Mild Neuropsychological Impairment at 90 Days and at 6 and 12 Months, as Measured by the Glasgow Coma Scale (GCS).

Detailed description: Herpes simplex encephalitis (HSE) remains the most common cause of sporadic fatal encephalitis in the world. This study is a phase III, double-blind, placebo controlled study of long term therapy with valacyclovir as a treatment of herpes encephalitis. The primary objective of this study is to assess the impact of valacyclovir (VACV) therapy (following standard intravenous acyclovir therapy) on neuropsychological impairment at one year post therapy, based on the cumulative scores of the Mattis Dementia Rating Scale (MDRS). The secondary objectives of the study are to: assess the effect of therapy on neuropsychological impairment at various time points; assess the effect of therapy on quality of life, based on the SF-36 Quality of Life Assessment; measure the effect of therapy on herpes simplex virus (HSV) deoxyribonucleic acid (DNA) in the cerebral spinal fluid (CSF); and assess the safety and tolerability of long term VACV therapy in patients with HSE. The tertiary objective of the study is to determine the frequency of symptomatic relapse/recurrence of HSE. Study participants will include 120 males and females, 12 years of age and older, diagnosed with HSE; laboratory confirmed CSF positive for HSV DNA by polymerase chain reaction (PCR). Consenting study participants will be randomized (1: 1) to either valacyclovir (active drug), 500 mg tablets, four tablets three times daily for 90 days or placebo (identical to active drug in appearance), 500 mg tablets, four tablets three times daily for 90 days. The primary endpoints of the study are to assess the impact of valacyclovir therapy [following standard intravenous acyclovir (ACV) therapy] on neuropsychological impairment at one year post therapy and survival with no or mild neuropsychological impairment at 12 months after initiation of study medication, as measured by the MDRS. The secondary endpoints include: survival with no or mild neuropsychological impairment at 90 days and at 6, 12 and 24 months, as measured by the MDRS, the Mini-Mental Status Examination (MMSE), and the Glasgow Coma Scale; effect of study medication on quality of life measurements; effect of antiviral therapy on HSV DNA in CSF (measured quantitatively by PCR at Day 0 and Day 90); and safety and tolerance of VACV administered at a dose of 2. 0 grams given orally three times a day for 90 days. Each study participant will participate for approximately 24 months.

Eligibility

Minimum age: 12 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

Inclusion Criteria:

- Informed consent and/or assent must be obtained from the patient or legal guardian.

- Patients with encephalopathy consistent with herpes simplex encephalitis (HSE) whose

cerebral spinal fluid (or brain biopsy sample) is positive for herpes simplex virus (HSV) deoxyribonucleic acid (DNA) by polymerase chain reaction (PCR).

- Patients who are receiving and will have completed intravenous (IV) acyclovir (ACV)

therapy for a minimum duration of 14 days to a maximum of 21 days and a minimum dose of 30 mg/kg/day to a maximum of 60 mg/kg/day, or equivalent dose as adjusted for renal dysfunction.

- Patient is expected to be available for follow-up visits of study drug administration

and through the 24 month study visit.

- Patients who are 12 years of age or older.

- Patients who weigh greater than or equal to 45. 5kg (100 pounds).

- All female patients with childbearing potential must have a negative pregnancy test

within 72 hours prior to initiation of study drug. If the pregnancy test is positive, the patient is ineligible for the study.

- Women must be post-menopausal, surgically sterile or willing to use adequate

contraception (barrier method with spermicide, intrauterine device (IUD), oral contraceptives, implant or other licensed hormone method) from time of study enrollment through 1 month after the last dose of study treatment.

- Men must be surgically sterile or willing to use contraception (barrier method with

spermicide) from time of study enrollment through 1 month after the last dose of study treatment. Exclusion Criteria:

- Patients with herpes simplex virus (HSV) meningitis only, without evidence of HSV

encephalitis.

- Patients with an anticipated life expectancy < 90 days.

- Patients with creatinine clearance of less than or equal to 50ml/min./1. 73 m^2.

- Pregnant or breastfeeding females.

- Patients who have received any anti-herpesvirus medication (e. g. ganciclovir) other

than intravenous acyclovir (ACV) for acute therapy of the current episode of herpes simplex encephalitis (HSE).

- Patients who are unable to swallow oral medications at the time of study drug

randomization (Day 0).

- Patients who are > 3 days beyond completion of treatment course with intravenous (IV)

ACV.

- Patients who are expected to receive long-term (> 30 days/year) therapy with

antiviral medications active against HSV [e. g. ACV, valacyclovir (VACV), famciclovir].

Locations and Contacts

University of Gothenburg - Sahlgrenska Academy, Gothenberg, Sweden

niversity of Lund - Infectious Disease, Lund, Sweden

Karolinska University Hospital, Huddinge, Stockholm, Sweden

Umea University - Infectious Diseases, Umea, Sweden

Uppsala University Hospital, Uppsala, Sweden

University College London - Royal Free Campus - Virology, London NW3 2PF, United Kingdom

University of Alabama at Birmingham, Birmingham, Alabama 35294-2050, United States

St. Joseph's Hospital and Medical Center - Barrow Neurological Institute - Phoenix, Phoenix, Arizona 85013, United States

University of California Davis Medical Center, Sacramento, California 95817, United States

University of Colorado, Denver, Colorado 80220, United States

Northwestern University Feinberg School of Medicine, Chicago, Illinois 60611, United States

University of Kansas Medical Center, Kansas City, Kansas 66160, United States

Tulane University Health Sciences Center, New Orleans, Louisiana 70112, United States

University of Manitoba - Medical Microbiology and Infectious Diseases, Winnipeg, Manitoba R3E 0W3, Canada

Johns Hopkins University, Baltimore, Maryland 21287, United States

Mayo Clinic, Rochester, Minnesota 55905, United States

Saint Louis University Hospital - School of Medicine - Department of Neurology & Psychiatry, St. Louis, Missouri 63110-0250, United States

University of New Mexico, Albuquerque, New Mexico 87131, United States

University of Toledo, Toledo, Ohio 43614, United States

Kingston General Hospital - Internal Medicine - Neurology, Kingston, Ontario K7L 2V7, Canada

University of Virginia Health System, Charlottesville, Virginia 22908, United States

Additional Information

Starting date: September 2000
Last updated: May 10, 2012

Page last updated: August 23, 2015

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