Acute Tonsillitis Clinical Trial
Official title:
A Multicenter, Randomized, Open, Comparative Study of Efficacy, Safety and Tolerability of Imupret Application in the Concept of Delayed Prescription of Antibiotics in Children, Aged 6-12 With Acute Tonsillitis
The problem of acute tonsillitis (AT) is one of the most urgent in modern clinical medicine.
The prevalence of pathology ranges from 2 to 15% of the total population.
AT (ICD J03.0-J03.9) in most cases is due to viral infections. Bacterial acute tonsillitis
occurs in immunocompetent children in 20-30% of cases.
To determine the indications for antibacterial therapy, the Mclsaac scale is a commonly used
tool for decision. This scale is used to classify patients according to their symptoms and to
determine the patients for whom antibiotic therapy is not indicated.
Thus, in most cases of acute tonsillitis (even if there are 4-5 points according to the
scale), it has to be taken into account that there is a low probability of the presence of
GABS. Therefore, there are no unconditional indications for the prescription of antibiotics.
Unjustified antibiotic therapy of AT plays a significant role in the formation of antibiotic
resistance.
To prevent unjustified prescription of antibiotics, a therapeutic concept of delayed
administration is proposed. A patient with AT is prescribed treatment with antibiotics in a
delayed manner. In the absence of a positive effect within 36-48 hours from the beginning of
treatment with Imupret, the antibacterial therapy is started. The advantage of deferred
antibiotic prescription is, that a higher number of patients and doctors, awaiting antibiotic
therapy, may be more agreeable with this way of treatment than with a complete rejection of
the antibiotic's prescription. So delayed use of antibiotics is an important treatment
strategy to reduce the number of unreasonable prescriptions of antibiotics.
Considering this fact, it becomes necessary to use drugs with a complex effect and
evidence-based efficacy base for acute tonsillitis. At the moment, there is an insignificant
evidence base for the application of the phytoneering drug Imupret in acute tonsillitis. The
spectrum of its pharmacological properties includes antiviral, antibacterial,
anti-inflammatory, and immunomodulating effects. The combination of these properties makes it
possible to influence practically all parts of acute tonsillitis. The already existing
studies were not conducted under GCP conditions. Confirmation of the high effectiveness of
Imupret in the treatment of acute tonsillitis would serve as a rationale for optimizing the
treatment regimen of this nosology and recommendations for the inclusion of the drug in
national guidelines.
Study of Therapeutic Efficacy, Safety, and Tolerability of Imupret application in the
therapeutic concept of delayed prescription of antibiotics in patients with severe acute
tonsillitis in children, aged 6-12.
Acute tonsillitis in most cases is due to viral infections. Bacterial tonsillitis occurs in
immunocompetent children in 20-30% of cases, adults - in 5-15%, and the most frequent cause
of it is β-hemolytic streptococcus group A (GABS).
Acute tonsillitis is defined as the sudden appearance of the following symptoms: sore throat,
hyperemia, edema of the tonsils, increase in swollen lymph nodes, and non-specific additional
symptoms like fever, weakness, and joint pain. There are no pathognomonic symptoms of
bacterial tonsillitis. To assess the patient's condition and to determine the indications for
antibacterial therapy, the Mclsaac scale is a commonly used tool for decision. This scale is
used to classify patients according to their symptoms and to determine the patients for whom
antibiotic therapy is not indicated.
McIsaac scale (sum of scores) The probability of the identification of β-hemolytic
streptococcus in a smear from pharynx -1 or 0 - 1% 1-10% 2 ~17% 3 ~35% 4 or 5 ~50% Thus, in
most cases of acute tonsillitis (even if there are 4-5 points according to the scale), it
must be considered that there is a low probability of the presence of GABS. Therefore, there
are no unconditional indications for the prescription of antibiotics.
Unjustified antibiotic therapy of acute tonsillitis based on "sore throat" or "exudate
(plaque) tonsils" only does not affect pain and lads the formation of antibiotic resistance.
In order to avoid the irrational use of antibiotics, one should distinguish the desire of the
patient or his parents to get rid of the pain, from the rational assessment of the doctor for
all pros and cons about an antibacterial therapy.
To prevent the unjustified prescription of antibiotics, a therapeutic concept of delayed
administration is proposed. A patient with acute tonsillitis is prescribed treatment with
antibiotics in a delayed manner. In the absence of positive dynamics within 36-48 hours from
the beginning of treatment with Imupret the antibacterial therapy is started. The advantage
of deferred antibiotic prescription is, that a higher number of patients and doctors,
awaiting antibiotic therapy, may be more agreeable with this way of treatment than with a
complete rejection of the antibiotic's prescription. Therefore, the delayed use of
antibiotics is an important treatment strategy to reduce the number of unreasonable
prescriptions of antibiotics.
Considering this fact, it becomes necessary to use drugs with a complex effect on the main
processes of pathogenesis and have an evidence-based efficacy for acute tonsillitis. Now,
there is an insignificant evidence base for the application of the herbal drug Imupret in
acute tonsillitis. The spectrum of its pharmacological properties includes antiviral,
antibacterial, anti-inflammatory, and immunomodulating effects. Additionally, a good safety
profile allows to consider Imupret as an adequate basic therapy for the treatment of acute
tonsillitis in the therapeutic concept of delayed prescription of antibiotics. The already
existing studies were not conducted under GCP conditions. Confirmation of the high
effectiveness of Imupret in the treatment of acute tonsillitis would serve as a rationale for
optimizing the treatment regimen of this nosology.
Proposed trial design: open-label, exploratory, comparative, multicenter, randomized,
prospective, parallel-group study.
Treatment:
The comparison group (n = 100): soft diet; elimination of factors that irritate the mucous
membrane of the pharynx (thermal, chemical); local NSAIDs - benzydamine hydrochloride (Tantum
Verde); acetaminophen as antipyretic if necessary.
The main group (n=100): soft diet; elimination of factors that irritate the mucous membrane
of the pharynx (thermal, chemical); local NSAIDs - benzydamine hydrochloride; Imupret oral
drops in the age-related dosage of 6 times per day for 6 days with the subsequent transition
to the regime of 15 drops / 3 times in a day according to the patient's condition;
acetaminophen as antipyretic, if necessary.
Schedule of visits. During the study, 3 planned visits: Visit 1 (The 1-st day): screening,
randomization, and treatment; evaluation by Mc Isaac Score scale; LTM Scale (Local
Tonsillitis Manifestation Scale): (5 symptoms: Sore throat at swallowing (0 - absent, 1 -
mild, 2 - moderate, 3 - severe / pronounced); Sore throat at rest; Throat irritation at rest;
Palatine tonsils hyperemia; Palatine tonsils edema); Patients self-assessment (VAS; 0-10).
Visit 2 (3rd±1 day): intermediate evaluation of the effectiveness of treatment -
clarification of the patient's condition, the need to prescribe an antibiotic; evaluation by
LTM Scale, patients' self-assessment (VAS; 0-10). Visit 3: intermediate evaluation of the
effectiveness of treatment (day 5-day ±1) via telephone (or visit if necessary); patients'
self-assessment (VAS; 0-10). Visit 4: final (10th day ±1 day). Evaluation by LTM Scale
(0-15), patients' self-assessment (VAS; 0-10). 5 Follow up; day 28: evaluation of the
long-term effects of treatment.
An unscheduled visit can be made if the patient's condition worsens (according to the patient
and/or the researcher, including if the symptoms of the disease persist or worsen, including
but not limited to an increase in the temperature in the armpit above 38.0 ° C at the 3rd
and/or subsequent days of treatment).
The total duration of the treatment: 10 days. The total duration of the study for one patient
is no longer than 38 days.
Objectives of the study: To investigate the influence of Imupret prescriptions in the
therapeutic concept of delayed prescription of antibiotics to:
- need for antibiotics;
- regression of the tonsillitis symptoms;
- duration of antipyretics administration.
Proposed parameters of interest:
- The severity of symptoms of tonsillitis, on the Visit 2 compared to the Visit 1. -
Indications for prescribing antibiotics (no positive dynamics or worsening of the
patient's condition).
- The decrease in the total score (the sum of scores for each symptom) according to the
LTM Scale (0-15), - Patients self-assessment (VAS; 0-10) scale of local manifestations
of tonsillitis at the V 2, V 3 and V 4 in comparison with the 1-st visit. - Decrease in
temperature in the armpit at the V 2 and V 3 compared to the Visit 1. - Self-evaluation
of the patient's quality of life. - Duration of NSAID administration
Statistical endpoints:
The main criterion (main variable):
- the decrease in the severity of each symptom (complaint) that is part of the scale of
tonsillitis manifestations, up to 1 point or less. This variable is dichotomous, with the
categories "treatment effective" and "treatment not effective": Treatment is effective -
reducing the severity of each symptom (complaint) that is part of the Local Tonsillitis
Manifestation Scale (0-15),of tonsillitis manifestations, up to 1 point or less in the
evaluation stages. Absence of indications for prescribing antibacterial therapy Treatment is
not effective - the condition is given for the category "therapy is effective" is not met.
Secondary variables:
- The decrease in the severity of the symptoms of the underlying disease, at the V 2, V 3
and V 4 visits compared to the 1-st visit.
- The decrease in the total score (the sum of scores for each symptom) according to the
scale of local manifestations of tonsillitis at the V 2, V 3 and V 4 in comparison with
the 1-st visit.
- Decrease in temperature in the armpit at the 2-nd and 3-rd visits compared to the 1-st
visit.
- Patient's self-assessment of the quality of life (every day).
- Duration of antipyretics administration. Statistical analysis is performed by a
statistician and includes descriptions of patients (included, completed and withdrawn),
adverse events and reactions, analysis of efficacy in each group, comparison of efficacy
between groups, safety assessment, and tolerability in each group. It is planned to use
the criteria of Shapiro-Wilk, Mann-Whitney (U).
Biometry: Patients with acute tonsillitis (N = 200): Age: 6-12 years old. The main group (n =
100). The control group (n = 100).
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