Effect of Bronchipret on Antiviral Immune Response in Patients With Mild COVID-19
- Registration Number
- NCT05276375
- Lead Sponsor
- Dr. Frank Behrens
- Brief Summary
There is currently an urgent need for effective and safe treatments of Coronavirus Disease (COVID) - 19 and the cytokine storm that is responsible for the development of patient's Acute Respiratory Distress Syndrome (ARDS).
As Bronchipret has been proven to be a very safe medicine, it is not expected that it would lead to the development of severe adverse effects in COVID-19 patients. Bronchipret can therefore be recommended as effective and safe supplementary treatments of COVID-19, even more so considering the positive effects shown in vitro. Thus, this randomized study is conducted to assess the effect of Bronchipret on the immune response and recovery in patients with mild COVID-19 by assessing several blood parameters as well as the symptom recovery and improvement in comparison to patients who do not receive Bronchipret. Another aim of this feasibility study is to determine the best possible primary endpoint, i.e. which shows the greatest effect according to Cohen.
- Detailed Description
Although intensive research efforts have been underway worldwide, so far, only few effective treatment against the disease has been brought to the market in Germany. Based on the pathological features and different clinical phases of COVID-19, particularly in patients with moderate to severe COVID- 19, the classes of drugs used are antiviral agents (e.g., remdesivir), inflammation inhibitors/antirheumatic drugs (e.g., dexamethasone), low molecular weight heparins, plasma, and hyperimmune immunoglobulins Bronchipret exhibits multidirectional anti-inflammatory effects as demonstrated in vitro and in vivo studies. Several clinical trials have demonstrated positive effects of Bronchipret, a fixed combination of thyme herb and ivy leaf fluid extracts, on symptom relieve and recovery time in patients with acute bronchitis and cough. There is currently an urgent need for effective and safe treatments of COVID- 19 and the cytokine storm that is responsible for the development of Acute Respiratory Distress Syndrome (ARDS).
As Bronchipret has been proven to be a very safe medicine, it is not expected that it would lead to the development of severe adverse effects in COVID-19 patients. Bronchipret can therefore be recommended as effective and safe supplementary treatments of COVID-19, even more so considering the positive effects shown in vitro. Thus, this randomized study will be conducted to assess the effect of Bronchipret on the immune response and recovery in patients with mild COVID-19 by assessing several blood parameters as well as the symptom recovery and improvement in comparison to patients who do not receive Bronchipret. Another aim of this feasibility study is to determine the best possible primary endpoint, i.e. which shows the greatest effect according to Cohen.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 21
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Patients ≥ 18 years and ≤ 75 years
o If > 50 years, complete COVID-19 vaccination mandatory
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SARS-CoV-2 infection confirmed by PCR test ≤ 4 days before screening/baseline visit
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Onset of the earliest symptoms < 7 days before screening/baseline visit
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Mild COVID-19 with the following symptoms (outpatient management/non hospitalized patients):
ᴑ Cough and ᴑ At least one other symptom (e.g., sore throat, nasal congestion, headache, nausea, low energy/fatigue, muscle or body ache, shortness of breath, fever, diarrhea, altered sense of smell or taste)
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Written informed consent obtained prior to the initiation of any protocol-required procedures by the patient
-
Willingness to comply to study procedures and study protocol
- WHO score ≥ 3
- Other advanced or chronic lung diseases (Chronic obstructive pulmonary disease (COPD), silicosis, bronchial asthma)
- Unable to take oral medication
- Body mass index (BMI) > 35 or ≤ 43kg
- Requirement for oxygen administration
- Current hospitalization
- Known hypersensitivity to the active substances ivy, thyme, plants of the aralia family or other labiates (Lamiaceae), birch, mugwort, celery or to any of the excipients
- Patients with rare hereditary fructose intolerance
- Inability to monitor body temperature
- Patients regularly taking immune suppressive medication, nonsteroidal anti-rheumatic drug(s) (NSARs) or steroids (e.g., because of underlying disease)
- Known significant concomitant diseases or serious and/or uncontrolled diseases that are likely to interfere with the evaluation of the patient's safety and with the study outcome such as stem cell or organ transplantation within the last 5 years, cardiovascular disease, diabetes mellitus, chronic liver disease, chronic kidney disease including dialysis patients, sickle cell anemia or thalassemia, and other forms of immunosuppression (e.g. tumor patients, HIV-infected patients with weakened immune system, iatrogenic immunosuppression) as judged by the study physician according to patient's reports.
- COVID-19 vaccination planned within study period and/or COVID-19 vaccination within the last 28 days
- Women pregnant (patient reported at pre-Screening and confirmation via pregnancy test at Screening/baseline) or nursing
- Males or females of reproductive potential not willing to use effective contraception (defined as PEARL index <1 - e.g. contraceptive pills/intra-uterine devices (IUD))
- Alcohol, drug or chemical abuse
- Current participation in another interventional clinical trial
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Bronchipret Bronchipret Bronchipret syrup (3x 5,4 ml daily, according to summary of product characteristics) until day 14
- Primary Outcome Measures
Name Time Method Change in average concentration of immunologic markers - Interferon y Comparison Baseline to day 7 concentration of interferon (INF) y
Change in average number of immunologic markers - monocytes Comparison Baseline to day 7 number of monocytes
Change in average concentration of immunologic markers Comparison Baseline to day 7 concentration of Interleukin 2 (IL-2)
Change in average concentration of immunologic markers - IL4 Comparison Baseline to day 7 concentration of Interleukin (IL) 4
Change in average concentration of immunologic markers - Interleukin (IL)-6 Comparison Baseline to day 7 concentration of IL-6
Change in average concentration of immunologic markers - IL-8 Comparison Baseline to day 7 concentration of IL-8
Change in average concentration of immunologic markers- c-reactive protein (CRP) Comparison Baseline to day 7 concentration of c-reactive protein (CRP)
Change in average number of immunologic markers - neutrophils Comparison Baseline to day 7 number of neutrophils
Change in average number of immunologic markers - eosinophils Comparison Baseline to day 7 number of eosinophils
Change in average concentration of immunologic markers - IL-10 Comparison Baseline to day 7 concentration of IL-10
Change in average number of immunologic markers - basophils Comparison Baseline to day 7 number of basophils
Change in average concentration of immunologic markers - IL-1β Comparison Baseline to day 7 concentration of IL-1β
Change in average concentration of immunologic markers - Interferon (INF) α Comparison Baseline to day 7 concentration of INFα
Change in average concentration of immunologic markers - TNFα Comparison Baseline to day 7 concentration of tumor necrosis factor alpha (TNFα)
Change in average number of immunologic markers - lymphocytes Comparison Baseline to day 7 number of lymphocytes
Change in average number of immunologic markers - platelets Comparison Baseline to day 7 number of platelets
- Secondary Outcome Measures
Name Time Method proportion of patients with fever Day 28 proportion of patients with fever
proportions of patients with COVID-19 vaccination Day 28 proportions of patients with COVID-19 vaccination
Concentration of blood parameters and change to BL - IL2 Day 4 percentage of change of concentration of IL-2
Concentration of blood parameters and change to BL (absolute change): IL2 Day 14 absolute change of concentration of IL-2
Concentration of blood parameters and change to BL (absolute change) IL4 Day 14 absolute change of concentration of IL-4
Concentration of blood parameters and change to BL (percentage) IL8 Day 4 percentage of change of concentration of IL-8
Concentration of blood parameters and change to BL (INFy percentage): Day 4 percentage of change of concentration of INFy
Concentration of blood parameters and change to BL (percentage): CRP Day 14 percentage of change of concentration of CRP
Concentration of blood parameters and change to BL (percentage): TNFα, Day 14 percentage of change of concentration of TNFα,
Concentration of blood parameters and change to BL (absolute change): neutrophils Day 14 absolute change of neutrophils number
Concentration of blood parameters and change to BL (absolute change) IL8 Day 4 absolute change of concentration of IL-8
Concentration of blood parameters and change to BL (absolute change IL8): Day 14 absolute change of concentration of IL-8
Concentration of blood parameters and change to BL (percentage): INFy Day 14 percentage of change of concentration of INFy
Concentration of blood parameters and change to BL Day 4 absolute change of concentration of IL-2
Concentration of blood parameters and change to BL (percentage): IL2 Day 14 percentage of change of concentration of IL-2
Concentration of blood parameters and change to BL (percentage) IL4 Day 14 percentage of change of concentration of IL-4
Concentration of blood parameters and change to BL (absolute change): IL4 Day 7 absolute change of concentration of IL-4
Concentration of blood parameters and change to BL (absolute change): Day 14 absolute change of Creatinin
Concentration of blood parameters and change to BL (absolute change IL10): Day 14 absolute change of concentration of IL-10
Concentration of blood parameters and change to BL (absolute change): lymphocytes Day 14 absolute change of lymphocytes number
Concentration of blood parameters and change to BL (absolute change) IL6 Day 14 absolute change of concentration of IL-6
Concentration of blood parameters and change to BL (percentage) IL6 Day 14 percentage of change of concentration of IL-6
Concentration of blood parameters and change to BL (percentage): IL10 Day 14 percentage of change of concentration of IL-10
Concentration of blood parameters and change to BL (absolute change):INFα Day 7 absolute change of concentration of INFα
Neutrophil to lymphocyte ratio Day 14 Neutrophil to lymphocyte number ratio
IL-6/INFy ratio Day 4 IL-6/INFy concentration ratio
Assessment of defervescence - number of patients Day 28 Number of patients who achieved defervescence
Concentration of blood parameters and change to BL (percentage): Day 14 percentage of change of Creatinin
Concentration of blood parameters and change to BL (absolute change): CRP Day 14 absolute change of concentration of CRP
Concentration of blood parameters and change to BL (percentage): INFα Day 14 percentage of change of concentration of INFα
Concentration of blood parameters and change to BL (percentage): lymphocytes Day 14 percentage change of lymphocytes
Concentration of blood parameters and change to BL (percentage): monocytes Day 14 percentage of change of monocytes
proportion of patients with hyposmia or anosmia Day 28 proportion of patients with hyposmia or anosmia
Number of recovered COVID-19 patients Day 28 Number of recovered COVID-19 patients
Concentration of blood parameters and change to BL (IL10 percentage): Day 4 percentage of change of concentration of IL-10
Concentration of blood parameters and change to BL (absolute change INFy): Day 4 absolute change of concentration of INFy
Concentration of blood parameters and change to BL (absolute change): INFy Day 14 absolute change of concentration of INFy
Concentration of blood parameters and change to BL (percentage): IL-1β Day 14 percentage of change of concentration of IL-1β
Concentration of blood parameters and change to BL (absolute change): IL-1β Day 14 absolute change of concentration of IL-1β
Concentration of blood parameters and change to BL (absolute change): INFα Day 14 absolute change of concentration of INFα
Concentration of blood parameters and change to BL (absolute change): TNFα, Day 14 absolute change of concentration of TNFα,
Concentration of blood parameters and change to BL (percentage): neutrophils Day 14 percentage change of neutrophils
Concentration of blood parameters and change to BL (percentage): eosinophils Day 14 percentage of change of eosinophils
Assessment of defervescence Day 28 Absolute temperature values and change to BL
Assessment of improvement or absence of coughing Day 28 proportion of patients who achieved cough reported as none existent
Assessment of improvement or absence of coughing - proportion of patients Day 28 proportion of patients with moderate or severe cough at BL who achieved cough reported as mild or none existent
Assessment of intensity and distribution of most bothersome symptom Day 28 Most bothersome symptom distribution (i.e.,number and percentage of patients with each symptom) (the most bothersome symptom will be defined by the patient at BL) assessment done by visual analogue scale (VAS) - score 0 to 10 cm, higher values describe higher intensity
Proportion of patients who return to usual health Day 28 proportion of patients who return to usual health
Requirement of hospitalisation or oxygen supplementation Day 28 proportion of patients requiring hospitalisation or oxygen supplementation (patient reported)
Assessment of intake of concomitant medication Day 14 proportion of patients with a reduction in concomitant medication intake
Concentration of blood parameters and change to BL (absolute change): monocytes Day 14 absolute change of monocytes number
Assessment of symptom distribution Day 28 FDA (Federal drug agency) recommended symptom questionnaire - higher scores describe worse symptoms, scoring 0 to 3 (question 1 to 12) and 0 to 2 (question 13 and 14)
proportion of patients who return to usual activity Day 28 proportion of patients who return to usual activity
Number of patients with hyposmia or anosmia Day 28 Number of patients with hyposmia or anosmia
Number of patients with fever Day 28 Number of patients with fever
proportion of recovered COVID-19 patients Day 28 proportion of recovered COVID-19 patients
Concentration of blood parameters and change to BL (absolute change): eosinophils Day 14 absolute change of eosinophils number
Assessment of symptom improvement/worsening Day 28 FDA (Federal drug agency) recommended symptom questionnaire - higher scores describe worse symptoms, scoring 0 to 3 (question 1 to 12) and 0 to 2 (question 13 and 14)
Assessment of number of symptoms Day 28 FDA (Federal drug agency) recommended symptom questionnaire - higher scores describe worse symptoms, scoring 0 to 3 (question 1 to 12) and 0 to 2 (question 13 and 14)
Number of patients who return to usual health Day 28 Number of patients who return to usual health
Assessment of severe acute respiratory syndrome (SARS)- Corona virus (CoV) -2 negativity Day 4 Assessment of SARS-CoV-2 negativity measured by polymerase chain reaction (PCR) test)
Number of adverse events (AE) through study completion, average 28 days Number of adverse events (AE)
IL-6/IL-10 ratio Day 14 IL-6/IL-10 concentration ratio
Assessment of defervescence - portion of patients Day 28 Proportion of patients who achieved defervescence
Disease progression/improvement Day 28 Number of patients in each disease severity state according to WHO score Score 0 - 10, higher score described more progressed state
Number of patients with COVID-19 vaccination Day 28 Number of patients with COVID-19 vaccination
Seriousness and relatedness of AEs through study completion, average 28 days Seriousness and relatedness of AEs
Assessment of improvement or absence of coughing - number of patients Day 28 Number of patients with moderate or severe cough at BL who achieved cough reported as mild or none existent
Assessment of oxygen saturation Day 28 Oxygen saturation measured by finger clip and change to BL
Assessment of SARS-CoV-2 negativity Day 28 Assessment of SARS-CoV-2 negativity measured by polymerase chain reaction (PCR) test)
Assessment of compliance Day 14 Compliance to IMP by dose taken and as documented in patient diary
Number of serious adverse events (SAE) through study completion, average 28 days Number of serious adverse events (SAE)
Type and severity of adverse events through study completion, average 28 days Type and severity of adverse events
Type and severity of serious adverse events through study completion, average 28 days Type and severity of serious adverse events
Seriousness and relatedness of SAEs through study completion, average 28 days Seriousness and relatedness of SAEs
Trial Locations
- Locations (1)
Fraunhofer ITMP - early clinical development
🇩🇪Frankfurt, Hessia, Germany