Encephalitis
Conditions
Keywords
encephalitis, herpes simplex, valacyclovir
Brief 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.
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.
Interventions
DRUGValacyclovir
Valacyclovir is a L-valyl ester of acyclovir. Valacyclovir is provided in 500 mg tablets, 4 tablets (500 mg tablets) 3 times a day (every 8 hours) for 90 days.
DRUGPlacebo
Placebo (identical to active drug in appearance) 500 mg tablets, 4 tablets 3 times daily for 90 days.
Sponsors
National Institute of Allergy and Infectious Diseases (NIAID)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
12 Years to No maximum
Healthy volunteers
No
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 \[e.g. ACV, valacyclovir (VACV), famciclovir\].
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Survival With no or Mild Neuropsychological Impairment at 12 Months After Initiation of Study Medication as Measured by the Mattis Dementia Rating Scale (MDRS) | One year post therapy. | Number of subjects who were assessed to have no or mild neuropsychological impairment at 12 months using the Mattis Dementia Rating Scale. (A score of 121 or higher refects no or mild neuropsychological impairment.) Scale is: 139-144 normal; 121-139 mild; 114-120 moderate; 87-113 severe; and \<=86 very severe. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Effect of Antiviral Therapy on Herpes Simplex Virus (HSV) Deoxyribonucleic Acid (DNA) in Cerebral Spinal Fluid (CSF) | Day 0 and Day 90. | Few CSF specimens were collected on day 90, hence unable to calculate the difference in PCR at day 0 and day 90.\[measured quantitatively by polymerase chain reaction (PCR)\]. |
| 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. | 6 months | The measure is the number of adverse events per subject. Adverse events were recorded from time of first dose of study drug through 6 months post start of study drug. |
| Effect of Study Medication on Quality of Life Measurements. | Day 0 and 90, Day 0 and Month 6 and Day 0 and Month 12 | The SF-36 Questionnaire measures quality of life as reported by the subject. The questionnaire contains 36 questions, each questions can be assigned a maximum score of 100. For each subject, a perfect score would be 3600, hence the higher score is best. The calculated scores reported in the table below reflect the diffence between Day 0 (day study drug started) and Day 90, Day 0 (day study drug started) and Month 6, and Day 0 (day study drug started) and Month 12. |
| 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). | 90 days, 6 and 12 months | The assessment score for the Mini-Mental Status Examination is as follows: 27 - 30: no neuropsychological impairment; 23 - 26: mild neuropsychological impairment; 16 - 22: moderate neuropsychological impairment; 11 - 15 severe neuropsychological impairment; and \<=10: very severe neuropsychological impairment. |
| Survival With no or Mild Neuropsychological Impairment at 90 Days and at 6 and 12 Months, as Measured by the Glasgow Coma Scale (GCS). | 90 days, 6 and 12 months | The assessment scoring for the Glasgow Coma Scale is as follows: 15: no neuropsychological impairment; 12 - 14: mild neuropsychological impairment; 9 - 11: moderate neuropsychological impairment; 6 to 8: severe neuropsychological impairment; and \<6: very severe neuropsychological impairment. |
| 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) | 90 days, 6 and 12 months | The assessment scoring for the Mattis Dementia Rating Scale is as follows: 139 - 144: no neuropsychological impairment; 121- 138: mild neuropsychological impairment; 114 - 120: moderate neuropsychological impairment; 87 - 113: severe neuropsychological impairment; and \<=86: very severe neuropsychological impairment. |
Countries
Canada, Sweden, United Kingdom, United States
Participant flow
Recruitment details
Subjects enrolled in the study presented with findings of HSE.
Pre-assignment details
Patients considered for enrollment are those who are receiving and will have completed IV Acyclovir for a minimum duration of 14 days to a maximum of 21 days at a minimum dose of 30 mg/kg/day to a maximum dose of 60 mg/kg/day.
Participants by arm
| Arm | Count |
|---|---|
| Valacyclovir four 500 mg tablets 3 times a day for 90 days | 40 |
| Placebo four placebo tablets (identical to active drug in appearance) 3 times a day for 90 days | 47 |
| Total | 87 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 |
| Overall Study | Death | 0 | 3 |
| Overall Study | Did not meet eligibility requirement | 2 | 1 |
| Overall Study | Lost to Follow-up | 0 | 1 |
| Overall Study | Non-compliant | 0 | 4 |
| Overall Study | Other | 1 | 1 |
| Overall Study | Withdrawal by Subject | 3 | 2 |
Baseline characteristics
| Characteristic | Valacyclovir | Placebo | Total |
|---|---|---|---|
| Age Continuous | 53.5 years | 56 years | 55 years |
| Age, Customized 12-18 years | 2 participants | 0 participants | 2 participants |
| Age, Customized 19-40 years | 7 participants | 5 participants | 12 participants |
| Age, Customized 41-60 years | 18 participants | 22 participants | 40 participants |
| Age, Customized 61 years or older | 13 participants | 20 participants | 33 participants |
| Region of Enrollment Canada | 6 participants | 4 participants | 10 participants |
| Region of Enrollment Sweden | 26 participants | 31 participants | 57 participants |
| Region of Enrollment United Kingdom | 0 participants | 3 participants | 3 participants |
| Region of Enrollment United States | 8 participants | 9 participants | 17 participants |
| Sex: Female, Male Female | 20 Participants | 20 Participants | 40 Participants |
| Sex: Female, Male Male | 20 Participants | 27 Participants | 47 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 36 / 40 | 39 / 47 |
| serious Total, serious adverse events | 16 / 40 | 29 / 47 |
Outcome results
Primary
Survival With no or Mild Neuropsychological Impairment at 12 Months After Initiation of Study Medication as Measured by the Mattis Dementia Rating Scale (MDRS)
Number of subjects who were assessed to have no or mild neuropsychological impairment at 12 months using the Mattis Dementia Rating Scale. (A score of 121 or higher refects no or mild neuropsychological impairment.) Scale is: 139-144 normal; 121-139 mild; 114-120 moderate; 87-113 severe; and \<=86 very severe.
Time frame: One year post therapy.
Population: All subjects that survived to 12 months and were assessed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Valacyclovir | Survival With no or Mild Neuropsychological Impairment at 12 Months After Initiation of Study Medication as Measured by the Mattis Dementia Rating Scale (MDRS) | MDRS Score >= 121 (positive) | 28 Participants |
| Valacyclovir | Survival With no or Mild Neuropsychological Impairment at 12 Months After Initiation of Study Medication as Measured by the Mattis Dementia Rating Scale (MDRS) | MDRS score < 121 (negative) | 5 Participants |
| Placebo | Survival With no or Mild Neuropsychological Impairment at 12 Months After Initiation of Study Medication as Measured by the Mattis Dementia Rating Scale (MDRS) | MDRS Score >= 121 (positive) | 34 Participants |
| Placebo | Survival With no or Mild Neuropsychological Impairment at 12 Months After Initiation of Study Medication as Measured by the Mattis Dementia Rating Scale (MDRS) | MDRS score < 121 (negative) | 2 Participants |
| Total | Survival With no or Mild Neuropsychological Impairment at 12 Months After Initiation of Study Medication as Measured by the Mattis Dementia Rating Scale (MDRS) | MDRS Score >= 121 (positive) | 62 Participants |
| Total | Survival With no or Mild Neuropsychological Impairment at 12 Months After Initiation of Study Medication as Measured by the Mattis Dementia Rating Scale (MDRS) | MDRS score < 121 (negative) | 7 Participants |
Secondary
Effect of Antiviral Therapy on Herpes Simplex Virus (HSV) Deoxyribonucleic Acid (DNA) in Cerebral Spinal Fluid (CSF)
Few CSF specimens were collected on day 90, hence unable to calculate the difference in PCR at day 0 and day 90.\[measured quantitatively by polymerase chain reaction (PCR)\].
Time frame: Day 0 and Day 90.
Population: The number of participants analyzed is 0 because there specimens obtained were inadequate and insufficient to analyze.
Secondary
Effect of Study Medication on Quality of Life Measurements.
The SF-36 Questionnaire measures quality of life as reported by the subject. The questionnaire contains 36 questions, each questions can be assigned a maximum score of 100. For each subject, a perfect score would be 3600, hence the higher score is best. The calculated scores reported in the table below reflect the diffence between Day 0 (day study drug started) and Day 90, Day 0 (day study drug started) and Month 6, and Day 0 (day study drug started) and Month 12.
Time frame: Day 0 and 90, Day 0 and Month 6 and Day 0 and Month 12
Population: All subjects that were assessed at baseline and the following time points: 90 days, 6 and 12 months.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Valacyclovir | Effect of Study Medication on Quality of Life Measurements. | SF-36 score difference from day 0 to 6 months | 722.5 Scores on a scale Change in SF-36 |
| Valacyclovir | Effect of Study Medication on Quality of Life Measurements. | SF-36 score difference from day 0 to 90 | 465 Scores on a scale Change in SF-36 |
| Valacyclovir | Effect of Study Medication on Quality of Life Measurements. | SF-36 score difference from day 0 to 12 months | 1095 Scores on a scale Change in SF-36 |
| Placebo | Effect of Study Medication on Quality of Life Measurements. | SF-36 score difference from day 0 to 6 months | 475 Scores on a scale Change in SF-36 |
| Placebo | Effect of Study Medication on Quality of Life Measurements. | SF-36 score difference from day 0 to 90 | 307.5 Scores on a scale Change in SF-36 |
| Placebo | Effect of Study Medication on Quality of Life Measurements. | SF-36 score difference from day 0 to 12 months | 985 Scores on a scale Change in SF-36 |
| Total | Effect of Study Medication on Quality of Life Measurements. | SF-36 score difference from day 0 to 90 | 355 Scores on a scale Change in SF-36 |
| Total | Effect of Study Medication on Quality of Life Measurements. | SF-36 score difference from day 0 to 12 months | 985 Scores on a scale Change in SF-36 |
| Total | Effect of Study Medication on Quality of Life Measurements. | SF-36 score difference from day 0 to 6 months | 635 Scores on a scale Change in SF-36 |
Secondary
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.
The measure is the number of adverse events per subject. Adverse events were recorded from time of first dose of study drug through 6 months post start of study drug.
Time frame: 6 months
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Valacyclovir | 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. | 8.5 Events per participants |
| Placebo | 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. | 8 Events per participants |
| Total | 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. | 8 Events per participants |
Secondary
Survival With no or Mild Neuropsychological Impairment at 90 Days and at 6 and 12 Months, as Measured by the Glasgow Coma Scale (GCS).
The assessment scoring for the Glasgow Coma Scale is as follows: 15: no neuropsychological impairment; 12 - 14: mild neuropsychological impairment; 9 - 11: moderate neuropsychological impairment; 6 to 8: severe neuropsychological impairment; and \<6: very severe neuropsychological impairment.
Time frame: 90 days, 6 and 12 months
Population: All subjects that survived and were assessed at 90 days, 6 and 12 months.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Valacyclovir | Survival With no or Mild Neuropsychological Impairment at 90 Days and at 6 and 12 Months, as Measured by the Glasgow Coma Scale (GCS). | GCS score >= 12 (90 days) | 30 Participants |
| Valacyclovir | Survival With no or Mild Neuropsychological Impairment at 90 Days and at 6 and 12 Months, as Measured by the Glasgow Coma Scale (GCS). | GCS score < 12 (90 days) | 0 Participants |
| Valacyclovir | Survival With no or Mild Neuropsychological Impairment at 90 Days and at 6 and 12 Months, as Measured by the Glasgow Coma Scale (GCS). | GCS score >= 12 (6 months) | 31 Participants |
| Valacyclovir | Survival With no or Mild Neuropsychological Impairment at 90 Days and at 6 and 12 Months, as Measured by the Glasgow Coma Scale (GCS). | GCS score < 12 (6 months) | 0 Participants |
| Valacyclovir | Survival With no or Mild Neuropsychological Impairment at 90 Days and at 6 and 12 Months, as Measured by the Glasgow Coma Scale (GCS). | GCS score >= 12 (12 months) | 33 Participants |
| Valacyclovir | Survival With no or Mild Neuropsychological Impairment at 90 Days and at 6 and 12 Months, as Measured by the Glasgow Coma Scale (GCS). | GCS score < 12 (12 months) | 0 Participants |
| Placebo | Survival With no or Mild Neuropsychological Impairment at 90 Days and at 6 and 12 Months, as Measured by the Glasgow Coma Scale (GCS). | GCS score < 12 (12 months) | 0 Participants |
| Placebo | Survival With no or Mild Neuropsychological Impairment at 90 Days and at 6 and 12 Months, as Measured by the Glasgow Coma Scale (GCS). | GCS score >= 12 (90 days) | 37 Participants |
| Placebo | Survival With no or Mild Neuropsychological Impairment at 90 Days and at 6 and 12 Months, as Measured by the Glasgow Coma Scale (GCS). | GCS score < 12 (6 months) | 0 Participants |
| Placebo | Survival With no or Mild Neuropsychological Impairment at 90 Days and at 6 and 12 Months, as Measured by the Glasgow Coma Scale (GCS). | GCS score >= 12 (12 months) | 37 Participants |
| Placebo | Survival With no or Mild Neuropsychological Impairment at 90 Days and at 6 and 12 Months, as Measured by the Glasgow Coma Scale (GCS). | GCS score < 12 (90 days) | 0 Participants |
| Placebo | Survival With no or Mild Neuropsychological Impairment at 90 Days and at 6 and 12 Months, as Measured by the Glasgow Coma Scale (GCS). | GCS score >= 12 (6 months) | 36 Participants |
| Total | Survival With no or Mild Neuropsychological Impairment at 90 Days and at 6 and 12 Months, as Measured by the Glasgow Coma Scale (GCS). | GCS score < 12 (90 days) | 0 Participants |
| Total | Survival With no or Mild Neuropsychological Impairment at 90 Days and at 6 and 12 Months, as Measured by the Glasgow Coma Scale (GCS). | GCS score >= 12 (6 months) | 67 Participants |
| Total | Survival With no or Mild Neuropsychological Impairment at 90 Days and at 6 and 12 Months, as Measured by the Glasgow Coma Scale (GCS). | GCS score < 12 (12 months) | 0 Participants |
| Total | Survival With no or Mild Neuropsychological Impairment at 90 Days and at 6 and 12 Months, as Measured by the Glasgow Coma Scale (GCS). | GCS score < 12 (6 months) | 0 Participants |
| Total | Survival With no or Mild Neuropsychological Impairment at 90 Days and at 6 and 12 Months, as Measured by the Glasgow Coma Scale (GCS). | GCS score >= 12 (90 days) | 67 Participants |
| Total | Survival With no or Mild Neuropsychological Impairment at 90 Days and at 6 and 12 Months, as Measured by the Glasgow Coma Scale (GCS). | GCS score >= 12 (12 months) | 70 Participants |
Secondary
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)
The assessment scoring for the Mattis Dementia Rating Scale is as follows: 139 - 144: no neuropsychological impairment; 121- 138: mild neuropsychological impairment; 114 - 120: moderate neuropsychological impairment; 87 - 113: severe neuropsychological impairment; and \<=86: very severe neuropsychological impairment.
Time frame: 90 days, 6 and 12 months
Population: All subjects that survived and were assessed at 90 days, 6 and 12 months.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Valacyclovir | 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) | MDRS score >= 121 (90 days) | 28 Participants |
| Valacyclovir | 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) | MDRS score < 121 (90 days) | 3 Participants |
| Valacyclovir | 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) | MDRS score >= 121 ( 6 months) | 24 Participants |
| Valacyclovir | 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) | MDRS score < 121 (6 months) | 5 Participants |
| Valacyclovir | 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) | MDRS score >= 121 (12 months) | 28 Participants |
| Valacyclovir | 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) | MDRS score < 121 (12 months) | 5 Participants |
| Placebo | 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) | MDRS score < 121 (12 months) | 2 Participants |
| Placebo | 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) | MDRS score >= 121 (90 days) | 31 Participants |
| Placebo | 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) | MDRS score < 121 (6 months) | 4 Participants |
| Placebo | 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) | MDRS score >= 121 (12 months) | 34 Participants |
| Placebo | 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) | MDRS score < 121 (90 days) | 5 Participants |
| Placebo | 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) | MDRS score >= 121 ( 6 months) | 31 Participants |
| Total | 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) | MDRS score < 121 (90 days) | 8 Participants |
| Total | 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) | MDRS score >= 121 ( 6 months) | 55 Participants |
| Total | 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) | MDRS score < 121 (12 months) | 7 Participants |
| Total | 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) | MDRS score < 121 (6 months) | 9 Participants |
| Total | 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) | MDRS score >= 121 (90 days) | 59 Participants |
| Total | 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) | MDRS score >= 121 (12 months) | 62 Participants |
Secondary
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).
The assessment score for the Mini-Mental Status Examination is as follows: 27 - 30: no neuropsychological impairment; 23 - 26: mild neuropsychological impairment; 16 - 22: moderate neuropsychological impairment; 11 - 15 severe neuropsychological impairment; and \<=10: very severe neuropsychological impairment.
Time frame: 90 days, 6 and 12 months
Population: All subjects that survived and were assessed at 90 days, 6 and 12 months.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Valacyclovir | 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). | MMSE score >= 23 (90 days) | 26 Participants |
| Valacyclovir | 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). | MMSE score < 23 (90 days) | 3 Participants |
| Valacyclovir | 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). | MMSE score >= 23 (6 months) | 23 Participants |
| Valacyclovir | 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). | MMSE score < 23 (6 months) | 4 Participants |
| Valacyclovir | 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). | MMSE score >= 23 (12 months) | 28 Participants |
| Valacyclovir | 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). | MMSE score < 23 (12 months) | 4 Participants |
| Placebo | 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). | MMSE score < 23 (12 months) | 5 Participants |
| Placebo | 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). | MMSE score >= 23 (90 days) | 31 Participants |
| Placebo | 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). | MMSE score < 23 (6 months) | 4 Participants |
| Placebo | 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). | MMSE score >= 23 (12 months) | 30 Participants |
| Placebo | 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). | MMSE score < 23 (90 days) | 5 Participants |
| Placebo | 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). | MMSE score >= 23 (6 months) | 29 Participants |
| Total | 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). | MMSE score < 23 (90 days) | 8 Participants |
| Total | 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). | MMSE score >= 23 (6 months) | 52 Participants |
| Total | 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). | MMSE score < 23 (12 months) | 9 Participants |
| Total | 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). | MMSE score < 23 (6 months) | 8 Participants |
| Total | 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). | MMSE score >= 23 (90 days) | 57 Participants |
| Total | 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). | MMSE score >= 23 (12 months) | 58 Participants |