Clinical trial • Infectious Disease | Neurology

Valaciclovir hydrochloride for Herpes simplex virus type 2 meningitis | Herpes simplex meningitis

Clinical trial of Valaciclovir hydrochloride for Herpes simplex virus type 2 meningitis | Herpes simplex meningitis.

Overview

Trial Therapeutic Area
Infectious Disease | Neurology
Trial Disease
Herpes simplex virus type 2 meningitis | Herpes simplex meningitis
Drug Modality
Small molecule

Key dates

Initial CTIS Submission Date
04-12-2024
First CTIS Authorization Date
02-01-2025

Trial design

Randomised, active treatment arms: aciclovir (intravenous solution; product: aciclovir pfizer 25 mg/ml, concentrate for infusion; max daily dose listed as 5 g; max treatment period 7 days) and valaciclovir (oral tablets; product: valaciclovir sandoz 500 mg film-coated tablet; product strength 500 mg, max daily dose listed as 3 g; max treatment period 7 days). comparator arms: matching iv and tablet placebos (iv and tablet placebos produced by euromed pharma services). detailed daily dosing schedule not specified in ctis record beyond product max daily doses and treatment period up to 7 days.-controlled trial across 8 sites in Denmark.

Randomised
Yes
Comparator
Active treatment arms: Aciclovir (intravenous solution; product: Aciclovir Pfizer 25 mg/ml, concentrate for infusion; max daily dose listed as 5 g; max treatment period 7 days) and Valaciclovir (oral tablets; product: Valaciclovir Sandoz 500 mg film-coated tablet; product strength 500 mg, max daily dose listed as 3 g; max treatment period 7 days). Comparator arms: matching IV and tablet placebos (IV and tablet placebos produced by Euromed Pharma Services). Detailed daily dosing schedule not specified in CTIS record beyond product max daily doses and treatment period up to 7 days.
Target Sample Size
150
Trial Duration For Participant
365

Eligibility

Recruits 150 No vulnerable populations selected; informed consent is required from participants. Subject information and informed consent forms are available (documents: L1_consent form AMEN Denmark; L1_SIS AMEN; L1_consent form with biobank). No assent or guardian consent procedures are specified in the CTIS record..

Pregnancy Exclusion
Pregnancy (proven by positive urine or plasma human chorionic gonadotropin test in fertile women)
Vulnerable Population
No vulnerable populations selected; informed consent is required from participants. Subject information and informed consent forms are available (documents: L1_consent form AMEN Denmark; L1_SIS AMEN; L1_consent form with biobank). No assent or guardian consent procedures are specified in the CTIS record.

Inclusion criteria

  • {"criterion_text":"- A clinical presentation consistent with viral meningitis (e.g. headache, nuchal rigidity, photophobia, or fever)\n- Cerebrospinal fluid (CSF) pleocytosis (>4 leukocytes x 106/L)\n- HSV-2 positive by PCR of the CSF\n- Glasgow Coma Scale score of 15\n- Ability to absorb oral medications"}

Exclusion criteria

  • {"criterion_text":"- Encephalitis as defined by the International Encephalitis Consortium if diagnosed during standard care\n- Systemic antiviral therapy with an antiherpetic effect for >24 hours\n- Previous enrolment into this trial\n- Transverse myelitis as defined by the Transverse Myelitis Consortium Working Group if diagnosed during standard care\n- Severe immuno-compromise defined as an ongoing need for biological- or chemotherapy (e.g. natalizumab), prednisolone >20 mg/day for ≥14 days, uncontrolled HIV/AIDS, haematological malignancies, and organ transplant recipients\n- Moderate to severe concomitant genital herpes requiring systemic aciclovir\n- Pregnancy (proven by positive urine or plasma human chorionic gonadotropin test in fertile women)\n- Hepatic impairment (aspartate aminotransferase or alanine aminotransferase levels >5 times the upper limit of normal)\n- Impaired renal function (estimated glomerular filtration rate <25 mL/min)\n- Intolerance to (val)aciclovir\n- Probenecid treatment"}

Endpoints

Primary endpoints

  • {"endpoint_text":"- The primary outcome in the current study is the proportion of patients with a TMS >6 at 7 days since randomisation.","definition_or_measurement_approach":"Proportion of patients with a Total Morbidity Score (TMS) >6 measured at 7 days after randomisation."}

Secondary endpoints

  • {"endpoint_text":"- Proportion of patients with ≤50% reduction in TMS score after 7 days compared with TMS score at randomisation\n- Unfavourable outcome (E-GOS <7) and all-cause mortality at 7 days, 3 and 12 months since randomisation\n- Proportion with a headache score of >2 at 7 days since randomisation\n- Persisting neurological symptoms (sensory or motor nerve) at 7 days, 3 and 12 months since randomisation\n- Completion of assigned treatment strategy\n- Peripheral venous line complications (infection or superficial venous thrombosis) during treatment\n- Duration of admission\n- Severe adverse events during treatment\n- Quality of life scores and cognitive evaluations (SF-36, EQ-5D-5L, Mental fatigue Scale) at 7 days as well as 3- and 12-months since randomisation","definition_or_measurement_approach":"Measures include change in TMS at 7 days vs baseline; E-GOS (<7) and all-cause mortality assessed at 7 days, 3 months and 12 months; headache score assessed at 7 days; presence of persisting neurological symptoms at specified timepoints; documentation of treatment completion; recording of peripheral venous line complications during treatment; length of hospital admission; recording of severe adverse events during treatment; quality of life and cognitive assessments using SF-36, EQ-5D-5L and Mental Fatigue Scale at 7 days, 3 months and 12 months."}

Recruitment

Planned Sample Size
150
Recruitment Window Months
60
Consent Approach
Informed consent is obtained from participants. Subject information and informed consent forms are provided (documents listed in CTIS: L1_consent form AMEN Denmark; L1_SIS AMEN; L1_consent form with biobank). No age-specific assent or guardian consent procedures or languages are specified in the CTIS record.

Geography

Total Number Of Sites
8
Total Number Of Participants
150

Denmark

Earliest CTIS Part Ii Submission Date
16-12-2024
Latest Decision Or Authorization Date
02-01-2025
Processing Time Days
17
Number Of Sites
8
Number Of Participants
150

Sites

Site Name
Hvidovre Hospital
Department Name
Infectious Diseases
Contact Person Name
Birgitte Rønde Hansen
Contact Person Email
brhansen@dadlnet.dk
Site Name
Rigshospitalet
Department Name
Infectious Diseases
Contact Person Name
Jannik Helweg-Larsen
Site Name
Aarhus University Hospital
Department Name
Infectious Diseases
Contact Person Name
Merete Storgaard
Contact Person Email
merestor@rm.dk
Site Name
Hillerod Hospital
Department Name
Infectious Diseases
Contact Person Name
Christian Thomas Brandt
Contact Person Email
chtb@regionh.dk
Site Name
Roskilde Hospital
Department Name
Infectious Diseases
Contact Person Name
Lothar Wiese
Contact Person Email
low@regionsjaelland.dk
Site Name
Odense University Hospital
Department Name
Infectious Diseases
Contact Person Name
Lykke Larsen
Contact Person Email
lykke.larsen@rsyd.dk
Site Name
Aalborg University Hospital
Department Name
Infectious Diseases
Contact Person Name
Henrik Nielsen
Contact Person Email
henrik.nielsen@rn.dk
Site Name
Herlev Hospital
Department Name
Infectious Diseases
Contact Person Name
Hans Rudolf Lüttichau

Sponsor

Primary sponsor

Full Name
Aalborg University Hospital
Organisation Type
Hospital/Clinic/Other health care facility
Country Of Registered Address
Denmark

Third parties

  • {"country":"Denmark","full_name":"Aalborg University Hospital","duties_or_roles":"sponsor duties code 1","organisation_type":"Hospital/Clinic/Other health care facility"}

Investigational products

Investigational Product Name
Valaciclovir Sandoz 500 mg compresse rivestite con film
Active Substance
Valaciclovir hydrochloride
Modality
Small molecule
Routes Of Administration
ORAL
Route
ORAL
Authorisation Status
Authorised (marketing authorisation number 039149188)
Starting Dose
500 mg (tablet)
Maximum Dose
3 g/day
Investigational Product Name
Aciclovir Pfizer 25 mg/ml, koncentrat till infusionsvätska, lösning
Active Substance
Aciclovir
Modality
Small molecule
Routes Of Administration
INTRAVENOUS
Route
INTRAVENOUS
Authorisation Status
Authorised (marketing authorisation number 14837)
Starting Dose
25 mg/ml concentrate for infusion
Maximum Dose
5 g/day
Investigational Product Name
IV and tablet placebo identifical to the active products will be produced by: Euromed Pharma Services S.R.L.
Modality
Other

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