Influenza
Conditions
Brief summary
The purpose of this study is: * to assess clinical efficiency of Ergoferon for treatment of influenza * to assess safety of Ergoferon for treatment of influenza * to compare efficiency of Ergoferon and Tamiflu for treatment of influenza
Interventions
DRUGErgoferon
Safety and Efficiency of Ergoferon in treatment of Influenza
DRUGOseltamivir
Safety and Efficiency in treatment of Influenza
Sponsors
Materia Medica Holding
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
No
Inclusion criteria
1. Patients of both sexes aged from 18 to 60 inclusively. 2. Patients with body temperature \>37,8°C at the moment of examination by the doctor; with at least one catarrh symptom (cough, rhinitis, sore throat) and one intoxication symptom (myalgia, fever/hyperhidrosis, malaise, weakness, headache) during seasonal influenza morbidity. 3. Diagnosed influenza confirmed by express diagnostics (presence of antigens of influenza virus in nasal passages epithelium and proved by QuickVue immunological test). 4. The possibility to start therapy within 24 hours after the onset of the first influenza symptoms. 5. Signed Informed Consent form for participation in the study.
Exclusion criteria
1. Patients aged below 18 years and above 60 years. 2. Suspected invasive bacterial infection or presence of severe disease requiring use of antibacterial drugs (including sulfanilamides). 3. Vaccination against influenza prior to epidemic season onset. 4. Medical history of polyvalent allergy. 5. Allergy/ intolerance to any of the components of medications used in the treatment. 6. Exacerbation or decompensation of chronic diseases affecting the patient's ability to participate in the clinical trial. 7. Chronic renal insufficiency. 8. Intake of medicines listed in the section Prohibited concomitant treatment for 15 days prior to the inclusion in the trial. 9. Pregnancy, breast feeding, unwillingness to keeping to contraception method during the study. 10. Drug addiction, alcohol usage in the amount over 2 units of alcohol per day. 11. Patients, who from investigator's point o view, will fail to comply with the observation requirements of the trial or with the intake regimen of the investigated medicines. 12. Participation in other clinical trials in the course of 1 month prior to the inclusion in the trial. 13. The patient is related to the research personnel of the investigative site, who are directly involved in the trial or are the immediate relative of the reseacher. The immediate relatives includes husband / wife, parents, children, brothers (or sisters), regardless of whether they are natural or adopted. 14. The patient works for OOO NPF Materia Medica Holding (i.e. is the company's employee, temporary contract worker or designated official responsible for carrying out the research) or the immediate relative.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Patients With Normal Body Temperature | Day 1 to Day 5 | Axillary temperature (morning and evening) decline to or below 37.0 ºС (without subsequent increase during ≥24 h) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to Resolution of the Influenza | Day 1 to Day 7 | Time to resolution was considered as time to the absence of any flu symptom. Absence of symptoms was considered as axillary temperature decline to or below 37.0 ºС without subsequent rise, resolution of the common and respiratory symptoms. The duration of a symptom was defined by physician recorded presence/absence of the symptoms during a physical examination at Day 1 to Day 7. |
| Mean Body Temperature | on days 1, 3 and 7 of the observation | The axillary temperature was assessed during a physical examination at Day 1, 3 and 7; axillary temperature was assessed in degrees (Celsius, °С) |
| Severity of Influenza Symptoms (Total Score of the Common Symptoms and Respiratory Symptoms) | on days 1, 3 and 7 of the observation | The severity of influenza symptoms was assessed during a physical examination at Day 1, 3 and 7; common (10 symptoms) and respiratory (5 symptoms) symptom's total score was assessed with using the point scale: 0=No symptom; 1=Mild symptom; 2=Moderate symptom ; 3=Severe symptom. The Common Symptoms total score ranged from 0 (no symptoms) to 30 (severe symptoms). The Respiration Symptoms total score ranged from 0 (no symptoms) to 15 (severe symptoms) |
| Percentage of Patients With Resolution of Influenza Symptoms | on the day 7 of the observation | Assessment of the proportion of subjects with no clinical symptoms of the disease (fever, common and respiratory symptoms) at Study Day 7 (Visit 3). The severity of influenza symptoms was assessed by a physician with 0 to 3 point scale, where 0 means no symptom, 1=mild symptom, 2=moderate symptom, and 3=severe symptom |
| Change in the Patient's Quality of Life. | Day 7 vs. Day 1 | The quality of life was assessed in influenza patients at baseline and at the end of the treatment period using the European Quality of Life Questionnaire (EQ5D) measuring the health status by five dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression (each dimension is assessed by 1 to 3 point scale; the minimum score 5 points refers to the best status, 15 points refers to the worst status). |
| Change in the Subjective Health Status | Day 7 vs. Day 1 | The patient subjective health status assessment was based on Visual Analogue Scale - VAS). VAS includes a rating of current health status from 0 (worst) to 100 (best). |
| Percentage of Patients With Complications of the Influenza | Day 1 to Day 7 | Pneumonia, sinusitis, otitis media are examples of the influenza complications |
| The Number of the Antipyretic Intake | Day 1 to Day 5 | A subject recorded the number of antipyretic intake in patient diary. |
Countries
Russia
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Ergoferon Group (EG) 1 tablet per 1 intake: on day 1 of the treatment 8 tablets (1 tablet every 30 minutes for the first 2 hours, then 1 tablet 3 times a day with equal intervals starting on the same day. From day 2 to day 5 1 tablet TID.
Ergoferon: Safety and Efficiency of Ergoferon in treatment of Influenza | 81 |
| Oseltamivir Group (OG) Oseltamivir(Tamiflu): Safety and Efficiency in treatment of Influenza | 80 |
| Total | 161 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 0 | 1 |
| Overall Study | Do not meet inclusion criteria | 1 | 2 |
| Overall Study | Insufficient data available | 0 | 1 |
| Overall Study | Protocol Violation | 1 | 0 |
Baseline characteristics
| Characteristic | Ergoferon Group (EG) | Oseltamivir Group (OG) | Total |
|---|---|---|---|
| Age, Continuous | 34.5 years STANDARD_DEVIATION 11.6 | 34.9 years STANDARD_DEVIATION 12.6 | 34.7 years STANDARD_DEVIATION 12.1 |
| Region of Enrollment Russian Federation | 81 participants | 80 participants | 161 participants |
| Sex: Female, Male Female | 49 Participants | 55 Participants | 104 Participants |
| Sex: Female, Male Male | 32 Participants | 25 Participants | 57 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 11 / 81 | 15 / 80 |
| serious Total, serious adverse events | 0 / 81 | 0 / 80 |
Outcome results
Primary
Percentage of Patients With Normal Body Temperature
Axillary temperature (morning and evening) decline to or below 37.0 ºС (without subsequent increase during ≥24 h)
Time frame: Day 1 to Day 5
Population: The Per Protocol (PP) set includes subjects received full per protocol therapy, completed all scheduled visits and had no substantial deviations from the protocol. Since PP-analysis and ITT-analysis demonstrated similar (confirmative) results the results of PP-analysis are presented.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Ergoferon Group (EG) | Percentage of Patients With Normal Body Temperature | Evening, Day 2 | 15 Percentage of participants |
| Ergoferon Group (EG) | Percentage of Patients With Normal Body Temperature | Evening, Day 4 | 68 Percentage of participants |
| Ergoferon Group (EG) | Percentage of Patients With Normal Body Temperature | Evening, Day 3 | 41 Percentage of participants |
| Ergoferon Group (EG) | Percentage of Patients With Normal Body Temperature | Evening, Day 5 | 84 Percentage of participants |
| Ergoferon Group (EG) | Percentage of Patients With Normal Body Temperature | Evening, Day 1 | 4 Percentage of participants |
| Oseltamivir Goup (OG) | Percentage of Patients With Normal Body Temperature | Evening, Day 5 | 88 Percentage of participants |
| Oseltamivir Goup (OG) | Percentage of Patients With Normal Body Temperature | Evening, Day 1 | 1 Percentage of participants |
| Oseltamivir Goup (OG) | Percentage of Patients With Normal Body Temperature | Evening, Day 2 | 15 Percentage of participants |
| Oseltamivir Goup (OG) | Percentage of Patients With Normal Body Temperature | Evening, Day 3 | 43 Percentage of participants |
| Oseltamivir Goup (OG) | Percentage of Patients With Normal Body Temperature | Evening, Day 4 | 72 Percentage of participants |
Comparison: PP set was analyzedp-value: 0.05Wald method of Z statistics calculation
Secondary
Change in the Patient's Quality of Life.
The quality of life was assessed in influenza patients at baseline and at the end of the treatment period using the European Quality of Life Questionnaire (EQ5D) measuring the health status by five dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression (each dimension is assessed by 1 to 3 point scale; the minimum score 5 points refers to the best status, 15 points refers to the worst status).
Time frame: Day 7 vs. Day 1
Population: Per Protocol set
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ergoferon Group (EG) | Change in the Patient's Quality of Life. | Day 7 | 5.4 Scores on a scale | Standard Deviation 0.9 |
| Ergoferon Group (EG) | Change in the Patient's Quality of Life. | Day 1 | 9.5 Scores on a scale | Standard Deviation 1.9 |
| Oseltamivir Goup (OG) | Change in the Patient's Quality of Life. | Day 1 | 9.4 Scores on a scale | Standard Deviation 2.2 |
| Oseltamivir Goup (OG) | Change in the Patient's Quality of Life. | Day 7 | 5.4 Scores on a scale | Standard Deviation 0.8 |
Comparison: PP set was analyzedp-value: <0.05t-test, 1 sided
Secondary
Change in the Subjective Health Status
The patient subjective health status assessment was based on Visual Analogue Scale - VAS). VAS includes a rating of current health status from 0 (worst) to 100 (best).
Time frame: Day 7 vs. Day 1
Population: Per Protocol set
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ergoferon Group (EG) | Change in the Subjective Health Status | Day 1 | 41.6 Scores on a scale | Standard Deviation 18.2 |
| Ergoferon Group (EG) | Change in the Subjective Health Status | Day 7 | 87.7 Scores on a scale | Standard Deviation 10.7 |
| Oseltamivir Goup (OG) | Change in the Subjective Health Status | Day 1 | 46.2 Scores on a scale | Standard Deviation 15.4 |
| Oseltamivir Goup (OG) | Change in the Subjective Health Status | Day 7 | 88.0 Scores on a scale | Standard Deviation 10.6 |
Comparison: PP set was analyzedp-value: <0.05t-test, 1 sided
Secondary
Mean Body Temperature
The axillary temperature was assessed during a physical examination at Day 1, 3 and 7; axillary temperature was assessed in degrees (Celsius, °С)
Time frame: on days 1, 3 and 7 of the observation
Population: Per Protocol set
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ergoferon Group (EG) | Mean Body Temperature | Axillary temperature, Day 1 | 38.3 °C | Standard Deviation 0.4 |
| Ergoferon Group (EG) | Mean Body Temperature | Axillary temperature, Day 3 | 37.0 °C | Standard Deviation 0.5 |
| Ergoferon Group (EG) | Mean Body Temperature | Axillary temperature, Day 7 | 36.5 °C | Standard Deviation 0.2 |
| Oseltamivir Goup (OG) | Mean Body Temperature | Axillary temperature, Day 1 | 38.3 °C | Standard Deviation 0.4 |
| Oseltamivir Goup (OG) | Mean Body Temperature | Axillary temperature, Day 3 | 37.0 °C | Standard Deviation 0.5 |
| Oseltamivir Goup (OG) | Mean Body Temperature | Axillary temperature, Day 7 | 36.6 °C | Standard Deviation 0.3 |
Comparison: PP set was analyzedp-value: <0.05t-test, 1 sided
Secondary
Percentage of Patients With Complications of the Influenza
Pneumonia, sinusitis, otitis media are examples of the influenza complications
Time frame: Day 1 to Day 7
Population: Per Protocol set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ergoferon Group (EG) | Percentage of Patients With Complications of the Influenza | 0 Percentage of participants |
| Oseltamivir Goup (OG) | Percentage of Patients With Complications of the Influenza | 2 Percentage of participants |
Comparison: PP set was analyzedp-value: <0.05The Wald method of Z statistics calcul
Secondary
Percentage of Patients With Resolution of Influenza Symptoms
Assessment of the proportion of subjects with no clinical symptoms of the disease (fever, common and respiratory symptoms) at Study Day 7 (Visit 3). The severity of influenza symptoms was assessed by a physician with 0 to 3 point scale, where 0 means no symptom, 1=mild symptom, 2=moderate symptom, and 3=severe symptom
Time frame: on the day 7 of the observation
Population: Per Protocol set.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Ergoferon Group (EG) | Percentage of Patients With Resolution of Influenza Symptoms | Fever | 100 Percentage of participants |
| Ergoferon Group (EG) | Percentage of Patients With Resolution of Influenza Symptoms | Common symptoms | 61 Percentage of participants |
| Ergoferon Group (EG) | Percentage of Patients With Resolution of Influenza Symptoms | Respiratory symptoms | 83 Percentage of participants |
| Ergoferon Group (EG) | Percentage of Patients With Resolution of Influenza Symptoms | All symptoms | 47 Percentage of participants |
| Oseltamivir Goup (OG) | Percentage of Patients With Resolution of Influenza Symptoms | All symptoms | 49 Percentage of participants |
| Oseltamivir Goup (OG) | Percentage of Patients With Resolution of Influenza Symptoms | Fever | 100 Percentage of participants |
| Oseltamivir Goup (OG) | Percentage of Patients With Resolution of Influenza Symptoms | Respiratory symptoms | 76 Percentage of participants |
| Oseltamivir Goup (OG) | Percentage of Patients With Resolution of Influenza Symptoms | Common symptoms | 64 Percentage of participants |
Comparison: PP set was analyzedp-value: <0.05Wald method of Z statistics calculation
Secondary
Severity of Influenza Symptoms (Total Score of the Common Symptoms and Respiratory Symptoms)
The severity of influenza symptoms was assessed during a physical examination at Day 1, 3 and 7; common (10 symptoms) and respiratory (5 symptoms) symptom's total score was assessed with using the point scale: 0=No symptom; 1=Mild symptom; 2=Moderate symptom ; 3=Severe symptom. The Common Symptoms total score ranged from 0 (no symptoms) to 30 (severe symptoms). The Respiration Symptoms total score ranged from 0 (no symptoms) to 15 (severe symptoms)
Time frame: on days 1, 3 and 7 of the observation
Population: Per Protocol set
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ergoferon Group (EG) | Severity of Influenza Symptoms (Total Score of the Common Symptoms and Respiratory Symptoms) | Common symptoms, Day 1 | 19.0 Scores on a scale | Standard Deviation 6.7 |
| Ergoferon Group (EG) | Severity of Influenza Symptoms (Total Score of the Common Symptoms and Respiratory Symptoms) | Common symptoms, Day 3 | 9.2 Scores on a scale | Standard Deviation 5.1 |
| Ergoferon Group (EG) | Severity of Influenza Symptoms (Total Score of the Common Symptoms and Respiratory Symptoms) | Common symptoms, Day 7 | 2.3 Scores on a scale | Standard Deviation 2.7 |
| Ergoferon Group (EG) | Severity of Influenza Symptoms (Total Score of the Common Symptoms and Respiratory Symptoms) | Respiratory symptoms, Day 1 | 6.1 Scores on a scale | Standard Deviation 3.7 |
| Ergoferon Group (EG) | Severity of Influenza Symptoms (Total Score of the Common Symptoms and Respiratory Symptoms) | Respiratory symptoms, Day 3 | 4.3 Scores on a scale | Standard Deviation 2.4 |
| Ergoferon Group (EG) | Severity of Influenza Symptoms (Total Score of the Common Symptoms and Respiratory Symptoms) | Respiratory symptoms, Day 7 | 1.3 Scores on a scale | Standard Deviation 1.5 |
| Oseltamivir Goup (OG) | Severity of Influenza Symptoms (Total Score of the Common Symptoms and Respiratory Symptoms) | Respiratory symptoms, Day 3 | 4.0 Scores on a scale | Standard Deviation 2.7 |
| Oseltamivir Goup (OG) | Severity of Influenza Symptoms (Total Score of the Common Symptoms and Respiratory Symptoms) | Common symptoms, Day 1 | 18.6 Scores on a scale | Standard Deviation 6.3 |
| Oseltamivir Goup (OG) | Severity of Influenza Symptoms (Total Score of the Common Symptoms and Respiratory Symptoms) | Respiratory symptoms, Day 1 | 5.9 Scores on a scale | Standard Deviation 3.6 |
| Oseltamivir Goup (OG) | Severity of Influenza Symptoms (Total Score of the Common Symptoms and Respiratory Symptoms) | Common symptoms, Day 3 | 7.8 Scores on a scale | Standard Deviation 4.3 |
| Oseltamivir Goup (OG) | Severity of Influenza Symptoms (Total Score of the Common Symptoms and Respiratory Symptoms) | Respiratory symptoms, Day 7 | 1.4 Scores on a scale | Standard Deviation 1.8 |
| Oseltamivir Goup (OG) | Severity of Influenza Symptoms (Total Score of the Common Symptoms and Respiratory Symptoms) | Common symptoms, Day 7 | 1.9 Scores on a scale | Standard Deviation 2.3 |
Comparison: PP set was analyzedp-value: <0.05t-test, 1 sided
Secondary
The Number of the Antipyretic Intake
A subject recorded the number of antipyretic intake in patient diary.
Time frame: Day 1 to Day 5
Population: Per Protocol set
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ergoferon Group (EG) | The Number of the Antipyretic Intake | Day 2 | 0.40 Number of Doses | Standard Deviation 0.49 |
| Ergoferon Group (EG) | The Number of the Antipyretic Intake | Day 4 | 0.01 Number of Doses | Standard Deviation 0.12 |
| Ergoferon Group (EG) | The Number of the Antipyretic Intake | Day 3 | 0.19 Number of Doses | Standard Deviation 0.39 |
| Ergoferon Group (EG) | The Number of the Antipyretic Intake | Day 5 | 0.00 Number of Doses | Standard Deviation 0 |
| Ergoferon Group (EG) | The Number of the Antipyretic Intake | Day 1 | 0.65 Number of Doses | Standard Deviation 0.48 |
| Oseltamivir Goup (OG) | The Number of the Antipyretic Intake | Day 5 | 0.01 Number of Doses | Standard Deviation 0.12 |
| Oseltamivir Goup (OG) | The Number of the Antipyretic Intake | Day 1 | 0.72 Number of Doses | Standard Deviation 0.45 |
| Oseltamivir Goup (OG) | The Number of the Antipyretic Intake | Day 2 | 0.49 Number of Doses | Standard Deviation 0.5 |
| Oseltamivir Goup (OG) | The Number of the Antipyretic Intake | Day 3 | 0.15 Number of Doses | Standard Deviation 0.36 |
| Oseltamivir Goup (OG) | The Number of the Antipyretic Intake | Day 4 | 0.03 Number of Doses | Standard Deviation 0.17 |
Comparison: PP set was analyzedp-value: <0.05t-test, 1 sided
Secondary
Time to Resolution of the Influenza
Time to resolution was considered as time to the absence of any flu symptom. Absence of symptoms was considered as axillary temperature decline to or below 37.0 ºС without subsequent rise, resolution of the common and respiratory symptoms. The duration of a symptom was defined by physician recorded presence/absence of the symptoms during a physical examination at Day 1 to Day 7.
Time frame: Day 1 to Day 7
Population: Per Protocol set
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ergoferon Group (EG) | Time to Resolution of the Influenza | Fever | 2.1 Days | Standard Deviation 1.4 |
| Ergoferon Group (EG) | Time to Resolution of the Influenza | Common symptoms | 2.6 Days | Standard Deviation 2.2 |
| Ergoferon Group (EG) | Time to Resolution of the Influenza | Respiratory symptoms | 2.7 Days | Standard Deviation 2.5 |
| Ergoferon Group (EG) | Time to Resolution of the Influenza | All influenza symptoms | 2.6 Days | Standard Deviation 2.3 |
| Oseltamivir Goup (OG) | Time to Resolution of the Influenza | All influenza symptoms | 2.5 Days | Standard Deviation 2.2 |
| Oseltamivir Goup (OG) | Time to Resolution of the Influenza | Fever | 2.3 Days | Standard Deviation 1.6 |
| Oseltamivir Goup (OG) | Time to Resolution of the Influenza | Respiratory symptoms | 2.6 Days | Standard Deviation 2.6 |
| Oseltamivir Goup (OG) | Time to Resolution of the Influenza | Common symptoms | 2.4 Days | Standard Deviation 2.1 |
Comparison: PP set was analyzedp-value: <0.05t-test, 1 sided