Clinical trial NCT04664127: Study of the Efficacy and Safety of Combined Treatment of Patients With Severe Herpes Simplex (HSV) Infection by Valacyclovir and Interferon Inducer Kagocel
Official title: Clinical and Immunological Study of the Efficacy and Safety of Combined Treatment of Patients With Severe Herpes Simplex (HSV) Infection) by Acyclic Nucleoside Valacyclovir and Interferon Inducer Kagocel
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Herpes
Herpes Simplex
Herpes Oral
Herpes Simplex 2
Herpes Genitalis
Keywords: herpes simplex
HSV1
HSV2
Herpes Genitalis
Herpes Oral
herpes simplex viruses
Valaciclovir
Lead sponsor: Nearmedic Plus LLC
Sponsor class: INDUSTRY
First posted: 2020-12-11
Enrollment: 45
Sex: ALL
Minimum age (years): 18
Maximum age (years): 100
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Adult men and women with signs of severe herpes simplex.

Brief summary: This study examined the efficacy, safety and benefits of modern treatment and changes in the dynamics of the life of adult patients quality with severe herpes simplex in the current medical practice when combined therapy by acyclic nucleoside Valacyclovir and antiviral agent Kagocel versus monotherapy by Valacyclovir. This study also evaluated the structure of herpesvirus infections and the rate of mixed variants of the course, the rate of exacerbations of herpes simplex, the time of disappearance of human herpesvirus isolation and the features of the immune phenotype of patients taking different types of therapy.

Detailed description: This study was a comparative post-registration prospective non-interventional (observational) scientific study.

This research did not include any procedures or medical interventions except those recommended in the local clinical guidelines and international standards of care. All procedures and evaluations were performed in accordance with routine clinical practice adopted in the Russian Federation and the instructions for the medical use of drugs that patients received.

The following data was collected and analyzed after the end of treatment:

* demography
* disease severity (mild, moderate, severe, continuous relapses)
* data of anamnesis (hereditary and family anamnesis, duration of herpes simplex disease, previous illnesses, duration of treatment, previous treatment of herpes simplex and its efficacy, allergic anamnesis, epidemiological anamnesis, rate and duration of herpes relapses over the past year (with indication of the location of herpes simplex rashes), main diagnosis and complications, ICD-10 code, date and time of the last exacerbation, causes of exacerbation)
* verification of inclusion criteria
* verification of non-inclusion criteria
* prescribed therapy (trade name and prescription scheme, rate, method of administration)
* laboratory tests (4 timelines: 1 - first 6-48 hours; 2 - 6 days after starting of therapy; 3 - 30 days; 4 - 4 months): clinical and biochemical blood tests; serological diagnostics with determination of herpes virus infections's markers: IgM, IgG-HSV1, HSV2; hospital screening of venous blood: anti - HIV-1,2; anti-HCV-total, HBsAg, CSR; microbiological seeding from the tonsils, posterior pharyngeal wall with determination of drug sensitivity; PCR of blood, saliva and/or rash elements; immune status by laser flow cytometry: CD3+, CD4+, CD8+, CD4+/CD8+, CD16+, CD19+; serum immunoglobulins: IgA, IgM, IgG, IgE total.
* medical anamnesis (4 timelines: 1 - first 6-48 hours; 2 - 6 days after starting of therapy; 3 - 30 days; 4 - 4 months) or clinical efficacy: the presence and rate of exacerbations of the disease orolabial, genital and other sites; local complaints; the rate of occurrence of and general symptoms; the rate of epithelialization of the rash's morphological elements; duration of recurrence of the herpes simplex virus and speed of onset of epithelialization; the rate of relapses and exacerbations of herpes simplex on the background of suppressive therapy
* taking other drugs during the study (trade name, prescription scheme)
* compliance with the drugs regimen
* timelines: data of signing the informed consent, start date of the study, date of each patient visit, end date of the study, start date and end date of the taking medicines, duration of patient follow-up)
* quality of life assessment at the end of the study (excellent / good / satisfactory / has not changed)
* adverse events (yes/no, data description)

Eligibility criteria: Inclusion Criteria:

* Patients ≥ 18 years old
* The absence of systemic etiotropic antiviral and immunosuppressive therapy for at least a year at the time of inclusion in this study
* Severe herpes simplex (HSV infection with orolabial and / or genital localization) with a recurrence rate of 6 or more for last 12 months.
* The first 6-48 hours after the exacerbation of herpes simplex.
* The following diseases and conditions are missing, usually requiring combination therapy by more than 2 drugs: ophthalmic herpes, visceral herpes, herpetic encephalitis, Kaposi's herpetiform eczema, primary immunodeficiency (PID criteria are given below\*), tuberculosis, ARVI and influenza symptoms (not related to herpesviruses), diabetes mellitus, hepatitis B and/or C, autoimmune diseases, HIV infection, other diseases requiring specific treatment (syphilis, gonorrhea), septic conditions, cancer (except of benign skin growths), mental illness, alcohol and/or drug addiction, artificial radiation and/or radiation therapy.
* Standard Valacyclovir therapy prescribed by doctor, or combination therapy by Valacyclovir and Kagocel.

Exclusion Criteria:

* Basic cytostatic therapy, taking systemic glucocorticoids for life indications. Treatment by immunoglobulins and any vaccines for 30 days prior to inclusion in the study.
* Early period (up to 1 month) after any vaccination.
* Pregnancy, including pregnancy planning for 3 months and lactation.
* The presence of a genetic disease or verified primary immunodeficiency.
* Anamnesis of transplantation of organs and tissues.
* Plasmapheresis and blood donation for less than 6 months before the present study.
* Severe kidney and liver damage.
* Any other diseases or conditions that, by the opinion of the researcher, may interfere the patient from being included in the study.

Primary outcomes:
measure: Change of the patients proportion with different localizations of herpes simplex exacerbations.
timeFrame: 2 points: before and 6 months after the start of therapy
measure: Change of the rate of exacerbations of orolabial, genital and other localization herpes simplex
timeFrame: 2 points: before and 6 months after the start of antiviral therapy
measure: Change of the number of patients with varying degrees of severity illness
timeFrame: 2 points: before and 6 months after the start of therapy
measure: Change in the number of local complaints (pain, itching, burning, rash) against the background of a recurrence of herpes simplex
timeFrame: up to 6 months
Secondary outcomes:
measure: Number of participants with treatment-related adverse events (AE) with regards to type and severity of AE (mild, moderate, severe; according to physician's opinion)
timeFrame: up to 6 (12) mounts
measure: Change of the duration of each herpes simplex relapse and the rate of epithelialization
timeFrame: 2 points: before and 6 days after the start of therapy
measure: Change of the occurrence rate of morphological elements of the rash and General symptoms
timeFrame: 4 points: 1-before the start of therapy, 2-6 days after the start of therapy, 3-30 days, 4-4 months
measure: Change of the rate of herpes simplex rash (relapses)
timeFrame: 4 points: 1 - before the start of therapy, 2 - 6 days after the start of therapy, 3 - 30 days, 4 - 4 months
measure: Change of the intensity of herpes simplex exacerbations in points
timeFrame: 4 points: 1-before the start of therapy, 2-6 days after the start of therapy, 3-30 days, 4-4 months
measure: Change in the number of herpes viruses in saliva and blood by PCR
timeFrame: 4 points: 1-before the start of therapy, 2-6 days after the start of therapy, 3-30 days, 4-4 months
measure: Change of antibodies titers to herpes simplex viruses type 1 and 2
timeFrame: 2 points: before the start of therapy and on the 30th day after the start of therapy
measure: Change of immune status parameters (flow cytometry)
timeFrame: 2 points: before treatment and at 30 days after initiation of therapy
measure: Change of immune status parameters (flow cytometry)
timeFrame: 2 points: before treatment and at 30 days after initiation of therapy
measure: Change of lymph nodes sizes (submandibular, axillary, inguinal) according to ultrasound data
timeFrame: 2 points: before and 6 months after the start of therapy
measure: The assessment of quality of life according to questionnaire
timeFrame: up to 6 months after initiation of therapy
Other outcomes:
Locations:
city: Moscow
country: Russian Federation
facility: Scientific Information Center for Prevention and Treatment of Viral Infections
Study officials:
affiliation: Scientific Information Center for Prevention and Treatment of Viral Infections
name: Georgy Vikulov, Ph.D
role: PRINCIPAL_INVESTIGATOR
References: