Effect of Bronchipret on Antiviral Immune Response in Patients With Mild COVID-19

Study Overview
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Brief Summary
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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
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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.

Official Title
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Effect of Bronchipret on Antiviral Immune Response in Patients With Mild COVID-19 (BroVID)

Conditions
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COVID-19

Intervention / Treatment
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* Drug: Bronchipret


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients ≥ 18 years and ≤ 75 years o If > 50 years, complete COVID-19 vaccination mandatory SARS-CoV-2 infection confirmed by PCR test ≤ 4 days before screening/baseline visit Onset of the earliest symptoms < 7 days before screening/baseline visit 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) 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 Exclusion Criteria: 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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Comparison of Verum (Bronchipret) versus no verum i.d. standard of care
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Bronchipret<br>Bronchipret syrup (3x 5,4 ml daily, according to summary of product characteristics) until day 14 | Drug: Bronchipret<br>* Bronchipret syrup (3x 5,4 ml daily) until day 14<br>|
| No Intervention: standard of care<br>no study intervention | |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in average concentration of immunologic markers | concentration of Interleukin 2 (IL-2) | Comparison Baseline to day 7 | 
| Change in average concentration of immunologic markers - IL4 | concentration of Interleukin (IL) 4 | Comparison Baseline to day 7 | 
| Change in average concentration of immunologic markers - Interleukin (IL)-6 | concentration of IL-6 | Comparison Baseline to day 7 | 
| Change in average concentration of immunologic markers - IL-8 | concentration of IL-8 | Comparison Baseline to day 7 | 
| Change in average concentration of immunologic markers - IL-10 | concentration of IL-10 | Comparison Baseline to day 7 | 
| Change in average concentration of immunologic markers - Interferon y | concentration of interferon (INF) y | Comparison Baseline to day 7 | 
| Change in average concentration of immunologic markers- c-reactive protein (CRP) | concentration of c-reactive protein (CRP) | Comparison Baseline to day 7 | 
| Change in average concentration of immunologic markers - IL-1β | concentration of IL-1β | Comparison Baseline to day 7 | 
| Change in average concentration of immunologic markers - Interferon (INF) α | concentration of INFα | Comparison Baseline to day 7 | 
| Change in average concentration of immunologic markers - TNFα | concentration of tumor necrosis factor alpha (TNFα) | Comparison Baseline to day 7 | 
| Change in average number of immunologic markers - neutrophils | number of neutrophils | Comparison Baseline to day 7 | 
| Change in average number of immunologic markers - lymphocytes | number of lymphocytes | Comparison Baseline to day 7 | 
| Change in average number of immunologic markers - monocytes | number of monocytes | Comparison Baseline to day 7 | 
| Change in average number of immunologic markers - eosinophils | number of eosinophils | Comparison Baseline to day 7 | 
| Change in average number of immunologic markers - basophils | number of basophils | Comparison Baseline to day 7 | 
| Change in average number of immunologic markers - platelets | number of platelets | Comparison Baseline to day 7 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Concentration of blood parameters and change to BL - IL2 | percentage of change of concentration of IL-2 | Day 4 | 
| Concentration of blood parameters and change to BL | absolute change of concentration of IL-2 | Day 4 | 
| Concentration of blood parameters and change to BL (percentage): IL2 | percentage of change of concentration of IL-2 | Day 7 | 
| Concentration of blood parameters and change to BL (absolute change): IL2 | absolute change of concentration of IL-2 | Day 7 | 
| Concentration of blood parameters and change to BL (absolute change): IL2 | absolute change of concentration of IL-2 | Day 14 | 
| Concentration of blood parameters and change to BL (percentage): IL2 | percentage of change of concentration of IL-2 | Day 14 | 
| Concentration of blood parameters and change to BL (percentage) IL4 | percentage of change of concentration of IL-4 | Day 4 | 
| Concentration of blood parameters and change to BL (absolute change): IL4 | absolute change of concentration of IL-4 | Day 7 | 
| Concentration of blood parameters and change to BL (percentage) IL4 | percentage of change of concentration of IL-4 | Day 7 | 
| Concentration of blood parameters and change to BL (absolute change) IL4 | absolute change of concentration of IL-4 | Day 14 | 
| Concentration of blood parameters and change to BL (percentage) IL4 | percentage of change of concentration of IL-4 | Day 14 | 
| Concentration of blood parameters and change to BL (absolute change) IL6 | absolute change of concentration of IL-6 | Day 4 | 
| Concentration of blood parameters and change to BL (percentage) IL6 | percentage of change of concentration of IL-6 | Day 4 | 
| Concentration of blood parameters and change to BL (absolute change) IL6 | absolute change of concentration of IL-6 | Day 7 | 
| Concentration of blood parameters and change to BL (percentage) IL6 | percentage of change of concentration of IL-6 | Day 7 | 
| Concentration of blood parameters and change to BL (percentage) IL6 | percentage of change of concentration of IL-6 | Day 14 | 
| Concentration of blood parameters and change to BL (absolute change) IL6 | absolute change of concentration of IL-6 | Day 14 | 
| Concentration of blood parameters and change to BL (percentage) IL8 | percentage of change of concentration of IL-8 | Day 4 | 
| Concentration of blood parameters and change to BL (absolute change) IL8 | absolute change of concentration of IL-8 | Day 4 | 
| Concentration of blood parameters and change to BL (percentage): | percentage of change of concentration of IL-8 | Day 7 | 
| Concentration of blood parameters and change to BL (absolute change): | absolute change of concentration of IL-8 | Day 7 | 
| Concentration of blood parameters and change to BL (percentage): | percentage of change of concentration of IL-8 | Day 14 | 
| Concentration of blood parameters and change to BL (absolute change IL8): | absolute change of concentration of IL-8 | Day 14 | 
| Concentration of blood parameters and change to BL (absolute change IL10): | absolute change of concentration of IL-10 | Day 4 | 
| Concentration of blood parameters and change to BL (IL10 percentage): | percentage of change of concentration of IL-10 | Day 4 | 
| Concentration of blood parameters and change to BL (absolute change IL10): | absolute change of concentration of IL-10 | Day 7 | 
| Concentration of blood parameters and change to BL (percentage): IL10 | percentage of change of concentration of IL-10 | Day 7 | 
| Concentration of blood parameters and change to BL (absolute change IL10): | absolute change of concentration of IL-10 | Day 14 | 
| Concentration of blood parameters and change to BL (percentage): IL10 | percentage of change of concentration of IL-10 | Day 14 | 
| Concentration of blood parameters and change to BL (INFy percentage): | percentage of change of concentration of INFy | Day 4 | 
| Concentration of blood parameters and change to BL (absolute change INFy): | absolute change of concentration of INFy | Day 4 | 
| Concentration of blood parameters and change to BL (percentage): INFy | percentage of change of concentration of INFy | Day 7 | 
| Concentration of blood parameters and change to BL (absolute change): INFy | absolute change of concentration of INFy | Day 7 | 
| Concentration of blood parameters and change to BL (percentage): INFy | percentage of change of concentration of INFy | Day 14 | 
| Concentration of blood parameters and change to BL (absolute change): INFy | absolute change of concentration of INFy | Day 14 | 
| Concentration of blood parameters and change to BL (absolute change): CRP | absolute change of concentration of CRP | Day 4 | 
| Concentration of blood parameters and change to BL (percentage): CRP | percentage of change of concentration of CRP | Day 4 | 
| Concentration of blood parameters and change to BL (absolute change): CRP | absolute change of concentration of CRP | Day 7 | 
| Concentration of blood parameters and change to BL (percentage): CRP | percentage of change of concentration of CRP | Day 7 | 
| Concentration of blood parameters and change to BL (absolute change): CRP | absolute change of concentration of CRP | Day 14 | 
| Concentration of blood parameters and change to BL (percentage): CRP | percentage of change of concentration of CRP | Day 14 | 
| Concentration of blood parameters and change to BL (percentage): IL-1β | percentage of change of concentration of IL-1β | Day 4 | 
| Concentration of blood parameters and change to BL (absolute change): IL-1β | absolute change of concentration of IL-1β | Day 4 | 
| Concentration of blood parameters and change to BL (percentage): IL-1β | percentage of change of concentration of IL-1β | Day 7 | 
| Concentration of blood parameters and change to BL (absolute change): IL-1β | absolute change of concentration of IL-1β | Day 7 | 
| Concentration of blood parameters and change to BL (percentage): IL-1β | percentage of change of concentration of IL-1β | Day 14 | 
| Concentration of blood parameters and change to BL (absolute change): IL-1β | absolute change of concentration of IL-1β | Day 14 | 
| Concentration of blood parameters and change to BL (absolute change): INFα | absolute change of concentration of INFα | Day 4 | 
| Concentration of blood parameters and change to BL (percentage): INFα | percentage of change of concentration of INFα | Day 4 | 
| Concentration of blood parameters and change to BL (absolute change):INFα | absolute change of concentration of INFα | Day 7 | 
| Concentration of blood parameters and change to BL (percentage): INFα | percentage of change of concentration of INFα | Day 7 | 
| Concentration of blood parameters and change to BL (percentage): INFα | percentage of change of concentration of INFα | Day 14 | 
| Concentration of blood parameters and change to BL (absolute change): INFα | absolute change of concentration of INFα | Day 14 | 
| Concentration of blood parameters and change to BL (absolute change): TNFα, | absolute change of concentration of TNFα, | Day 4 | 
| Concentration of blood parameters and change to BL (percentage): TNFα, | percentage of change of concentration of TNFα, | Day 4 | 
| Concentration of blood parameters and change to BL (absolute change): TNFα, | absolute change of concentration of TNFα, | Day 7 | 
| Concentration of blood parameters and change to BL (percentage): TNFα, | percentage of concentration of TNFα, | Day 7 | 
| Concentration of blood parameters and change to BL (absolute change): TNFα, | absolute change of concentration of TNFα, | Day 14 | 
| Concentration of blood parameters and change to BL (percentage): TNFα, | percentage of change of concentration of TNFα, | Day 14 | 
| Concentration of blood parameters and change to BL (percentage): neutrophils | percentage change of neutrophils | Day 4 | 
| Concentration of blood parameters and change to BL (absolute change): neutrophils | absolute change of neutrophils number | Day 4 | 
| Concentration of blood parameters and change to BL (percentage): neutrophils | percentage change of neutrophils | Day 7 | 
| Concentration of blood parameters and change to BL (absolute change): neutrophils | absolute change of neutrophils number | Day 7 | 
| Concentration of blood parameters and change to BL (percentage): neutrophils | percentage change of neutrophils | Day 14 | 
| Concentration of blood parameters and change to BL (absolute change): neutrophils | absolute change of neutrophils number | Day 14 | 
| Concentration of blood parameters and change to BL (absolute change): lymphocytes | absolute change of lymphocytes number | Day 4 | 
| Concentration of blood parameters and change to BL (percentage): lymphocytes | percentage change of lymphocytes | Day 4 | 
| Concentration of blood parameters and change to BL (absolute change): lymphocytes | absolute change of lymphocytes number | Day 7 | 
| Concentration of blood parameters and change to BL (percentage): lymphocytes | percentage change of lymphocytes | Day 7 | 
| Concentration of blood parameters and change to BL (absolute change): lymphocytes | absolute change of lymphocytes number | Day 14 | 
| Concentration of blood parameters and change to BL (percentage): lymphocytes | percentage change of lymphocytes | Day 14 | 
| Concentration of blood parameters and change to BL (percentage): monocytes | percentage change of monocytes | Day 4 | 
| Concentration of blood parameters and change to BL (absolute change): monocytes | absolute change of monocytes number | Day 4 | 
| Concentration of blood parameters and change to BL (percentage): monocytes | percentage change of monocytes | Day 7 | 
| Concentration of blood parameters and change to BL (absolute change): monocytes | absolute change of monocytes number | Day 7 | 
| Concentration of blood parameters and change to BL (percentage): monocytes | percentage of change of monocytes | Day 14 | 
| Concentration of blood parameters and change to BL (absolute change): monocytes | absolute change of monocytes number | Day 14 | 
| Concentration of blood parameters and change to BL (absolute change): eosinophils | absolute change of eosinophils number | Day 4 | 
| Concentration of blood parameters and change to BL (percentage): eosinophils | percentage of change of eosinophils | Day 4 | 
| Concentration of blood parameters and change to BL (percentage): eosinophils | percentage of change of eosinophils | Day 7 | 
| Concentration of blood parameters and change to BL (absolute change): eosinophils | absolute change of eosinophils number | Day 7 | 
| Concentration of blood parameters and change to BL (percentage): eosinophils | percentage of change of eosinophils | Day 14 | 
| Concentration of blood parameters and change to BL (absolute change): eosinophils | absolute change of eosinophils number | Day 14 | 
| Concentration of blood parameters and change to BL (percentage): | percentage of change of basophils number | Day 4 | 
| Concentration of blood parameters and change to BL (absolute change): | absolute change of basophils number | Day 4 | 
| Concentration of blood parameters and change to BL (absolute change): | absolute change of basophils number | Day 7 | 
| Concentration of blood parameters and change to BL (percentage): | percentage of change of basophils | Day 7 | 
| Concentration of blood parameters and change to BL (absolute change): | absolute change of basophils number | Day 14 | 
| Concentration of blood parameters and change to BL (percentage): | percentage of change of basophils | Day 14 | 
| Concentration of blood parameters and change to BL (percentage): | percentage of change of platelets | Day 4 | 
| Concentration of blood parameters and change to BL (absolute change): | absolute change of platelet number | Day 4 | 
| Concentration of blood parameters and change to BL (percentage): | percentage of change of platelets | Day 7 | 
| Concentration of blood parameters and change to BL (absolute change): | absolute change of platelet number | Day 7 | 
| Concentration of blood parameters and change to BL (percentage): | percentage of change of platelets | Day 14 | 
| Concentration of blood parameters and change to BL (absolute change): | absolute change of platelet number | Day 14 | 
| Concentration of blood parameters and change to BL (percentage): | percentage of change of lactate dehydrogenase (LDH) | Day 4 | 
| Concentration of blood parameters and change to BL (absolute change): | absolute change of lactate dehydrogenase (LDH) | Day 4 | 
| Concentration of blood parameters and change to BL (absolute change): | absolute change of LDH | Day 7 | 
| Concentration of blood parameters and change to BL (percentage): | percentage of change of LDH | Day 7 | 
| Concentration of blood parameters and change to BL (absolute change): | absolute change of LDH | Day 14 | 
| Concentration of blood parameters and change to BL (percentage): | percentage of change of LDH | Day 14 | 
| Concentration of blood parameters and change to BL (percentage): | percentage of change of ferritin | Day 4 | 
| Concentration of blood parameters and change to BL (absolute change): | absolute change of ferritin | Day 4 | 
| Concentration of blood parameters and change to BL (percentage): | percentage of change of ferritin | Day 7 | 
| Concentration of blood parameters and change to BL (absolute change): | absolute change of ferritin | Day 7 | 
| Concentration of blood parameters and change to BL (percentage): | percentage of change of ferritin | Day 14 | 
| Concentration of blood parameters and change to BL (absolute change): | absolute change of ferritin | Day 14 | 
| Concentration of blood parameters and change to BL (absolute change): | absolute change of haemoglobin | Day 4 | 
| Concentration of blood parameters and change to BL (percentage): | percentage of change of haemoglobin | Day 4 | 
| Concentration of blood parameters and change to BL (absolute change): | absolute change of haemoglobin | Day 7 | 
| Concentration of blood parameters and change to BL (percentage): | percentage of change of haemoglobin | Day 7 | 
| Concentration of blood parameters and change to BL (absolute change): | absolute change of haemoglobin | Day 14 | 
| Concentration of blood parameters and change to BL (percentage): | percentage of change of haemoglobin | Day 14 | 
| Concentration of blood parameters and change to BL (absolute change): | absolute change of alanine aminotransferase (ALT) | Day 4 | 
| Concentration of blood parameters and change to BL (percentage): | percentage of change of alanine aminotransferase (ALT) | Day 4 | 
| Concentration of blood parameters and change to BL (absolute change): | absolute change of alanine aminotransferase (ALT) | Day 7 | 
| Concentration of blood parameters and change to BL (percentage): | percentage of change of alanine aminotransferase (ALT) | Day 7 | 
| Concentration of blood parameters and change to BL (percentage): | percentage of change of alanine aminotransferase (ALT) | Day 14 | 
| Concentration of blood parameters and change to BL (absolute change): | absolute change of alanine aminotransferase (ALT) | Day 14 | 
| Concentration of blood parameters and change to BL (absolute change): | absolute change of Aspartate aminotransferase (AST) | Day 4 | 
| Concentration of blood parameters and change to BL (absolute change): | absolute change of Aspartate aminotransferase (AST) | Day 7 | 
| Concentration of blood parameters and change to BL (percentage): | percentage of change of Aspartate aminotransferase (AST) | Day 7 | 
| Concentration of blood parameters and change to BL (absolute change): | absolute change of Aspartate aminotransferase (AST) | Day 14 | 
| Concentration of blood parameters and change to BL (percentage): | percentage of change of Aspartate aminotransferase (AST) | Day 14 | 
| Concentration of blood parameters and change to BL (percentage): | percentage of change of activated partial thromboplastin time | Day 4 | 
| Concentration of blood parameters and change to BL (absolute change): | absolute change of activated partial thromboplastin time | Day 4 | 
| Concentration of blood parameters and change to BL (absolute change): | absolute change of activated partial thromboplastin time | Day 7 | 
| Concentration of blood parameters and change to BL (percentage): | percentage of change of activated partial thromboplastin time | Day 7 | 
| Concentration of blood parameters and change to BL (percentage): | percentage of change of activated partial thromboplastin time | Day 14 | 
| Concentration of blood parameters and change to BL (absolute change): | absolute change of activated partial thromboplastin time | Day 14 | 
| Concentration of blood parameters and change to BL (absolute change): | absolute change of prothrombin Z | Day 4 | 
| Concentration of blood parameters and change to BL (percentage): | percentage of change of prothrombin Z | Day 4 | 
| Concentration of blood parameters and change to BL (absolute change): | absolute change of prothrombin Z | Day 7 | 
| Concentration of blood parameters and change to BL (percentage): | percentage of change of prothrombin Z | Day 7 | 
| Concentration of blood parameters and change to BL (absolute change): | absolute change of prothrombin Z | Day 14 | 
| Concentration of blood parameters and change to BL (percentage): | percentage of change of prothrombin Z | Day 14 | 
| Concentration of blood parameters and change to BL (percentage): | percentage of change of fibrinogen | Day 4 | 
| Concentration of blood parameters and change to BL (absolute change): | absolute change of fibrinogen | Day 4 | 
| Concentration of blood parameters and change to BL (percentage): | percentage of change of fibrinogen | Day 7 | 
| Concentration of blood parameters and change to BL (absolute change): | absolute change of fibrinogen | Day 7 | 
| Concentration of blood parameters and change to BL (percentage): | percentage of change of fibrinogen | Day 14 | 
| Concentration of blood parameters and change to BL (absolute change): | absolute change of fibrinogen | Day 14 | 
| Concentration of blood parameters and change to BL (absolute change): | absolute change of d-dimeric | Day 4 | 
| Concentration of blood parameters and change to BL (percentage): | percentage of change of d-dimeric | Day 4 | 
| Concentration of blood parameters and change to BL (absolute change): | absolute change of d-dimeric | Day 7 | 
| Concentration of blood parameters and change to BL (percentage): | percentage of change of d-dimeric | Day 7 | 
| Concentration of blood parameters and change to BL (absolute change): | absolute change of d-dimeric | Day 14 | 
| Concentration of blood parameters and change to BL (percentage): | percentage of change of d-dimeric | Day 14 | 
| Concentration of blood parameters and change to BL (percentage): | percentage of change of fibrin-degranulation products | Day 4 | 
| Concentration of blood parameters and change to BL (absolute change): | absolute change of fibrin-degranulation products | Day 4 | 
| Concentration of blood parameters and change to BL (percentage): | percentage of change of fibrin-degranulation products | Day 7 | 
| Concentration of blood parameters and change to BL (absolute change): | absolute change of fibrin-degranulation products | Day 7 | 
| Concentration of blood parameters and change to BL (percentage): | percentage of change of fibrin-degranulation products | Day 14 | 
| Concentration of blood parameters and change to BL (absolute change): | absolute change of fibrin-degranulation products | Day 14 | 
| Concentration of blood parameters and change to BL (absolute change): | absolute change of anti-thrombin III activity | Day 4 | 
| Concentration of blood parameters and change to BL (percentage): | percentage of change of anti-thrombin III activity | Day 4 | 
| Concentration of blood parameters and change to BL (absolute change): | absolute change of anti-thrombin III activity | Day 7 | 
| Concentration of blood parameters and change to BL (percentage): | percentage of change of anti-thrombin III activity | Day 7 | 
| Concentration of blood parameters and change to BL (absolute change): | absolute change of anti-thrombin III activity | Day 14 | 
| Concentration of blood parameters and change to BL (percentage): | percentage of change of anti-thrombin III activity | Day 14 | 
| Concentration of blood parameters and change to BL (percentage): | percentage of change of Immunglobulin M (IgM) | Day 4 | 
| Concentration of blood parameters and change to BL (absolute change): | absolute change of Immunglobulin M (IgM) | Day 4 | 
| Concentration of blood parameters and change to BL (percentage): | percentage of change of Immunglobulin M (IgM) | Day 7 | 
| Concentration of blood parameters and change to BL (absolute change): | absolute change of Immunglobulin M (IgM) | Day 7 | 
| Concentration of blood parameters and change to BL (percentage): | percentage of change of Immunglobulin M (IgM) | Day 14 | 
| Concentration of blood parameters and change to BL (absolute change): | absolute change of Immunglobulin M (IgM) | Day 14 | 
| Concentration of blood parameters and change to BL (absolute change): | absolute change of Immunglobulin G (IgG) | Day 4 | 
| Concentration of blood parameters and change to BL (percentage): | percentage of change of Immunglobulin G (IgG) | Day 4 | 
| Concentration of blood parameters and change to BL (absolute change): | absolute change of Immunglobulin G (IgG) | Day 7 | 
| Concentration of blood parameters and change to BL (percentage): | percentage of change of Immunglobulin G (IgG) | Day 7 | 
| Concentration of blood parameters and change to BL (absolute change): | absolute change of Immunglobulin G (IgG) | Day 14 | 
| Concentration of blood parameters and change to BL (percentage): | percentage of change of Immunglobulin G (IgG) | Day 14 | 
| Concentration of blood parameters and change to BL (percentage): | percentage of change of Creatinin | Day 4 | 
| Concentration of blood parameters and change to BL (absolute change): | absolute change of Creatinin | Day 4 | 
| Concentration of blood parameters and change to BL (percentage): | percentage of change of Creatinin | Day 7 | 
| Concentration of blood parameters and change to BL (absolute change): | absolute change of Creatinin | Day 7 | 
| Concentration of blood parameters and change to BL (percentage): | percentage of change of Creatinin | Day 14 | 
| Concentration of blood parameters and change to BL (absolute change): | absolute change of Creatinin | Day 14 | 
| Neutrophil to lymphocyte ratio | Neutrophil to lymphocyte number ratio | Day 4 | 
| Neutrophil to lymphocyte ratio | Neutrophil to lymphocyte number ratio | Day 7 | 
| Neutrophil to lymphocyte ratio | Neutrophil to lymphocyte number ratio | Day 14 | 
| IL-6/IL-10 ratio | IL-6/IL-10 concentration ratio | Day 4 | 
| IL-6/IL-10 ratio | IL-6/IL-10 concentration ratio | Day 7 | 
| IL-6/IL-10 ratio | IL-6/IL-10 concentration ratio | Day 14 | 
| IL-6/INFy ratio | IL-6/INFy concentration ratio | Day 14 | 
| IL-6/INFy ratio | IL-6/INFy concentration ratio | Day 7 | 
| IL-6/INFy ratio | IL-6/INFy concentration ratio | Day 4 | 
| Assessment of symptom improvement/worsening | 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) | Day 4 | 
| Assessment of symptom improvement/worsening | 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) | Day 7 | 
| Assessment of symptom improvement/worsening | 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) | Day 14 | 
| Assessment of symptom improvement/worsening | 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) | Day 28 | 
| Assessment of number of symptoms | 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) | Day 4 | 
| Assessment of number of symptoms | 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) | Day 7 | 
| Assessment of number of symptoms | 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) | Day 14 | 
| Assessment of number of symptoms | 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) | Day 28 | 
| Assessment of symptom distribution | 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) | Day 4 | 
| Assessment of symptom distribution | 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) | Day 7 | 
| Assessment of symptom distribution | 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) | Day 14 | 
| Assessment of symptom distribution | 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) | Day 28 | 
| Assessment of defervescence | Time to defervescence in days | Day 28 | 
| Assessment of defervescence - number of patients | Number of patients who achieved defervescence | Day 28 | 
| Assessment of defervescence - portion of patients | Proportion of patients who achieved defervescence | Day 28 | 
| Assessment of defervescence | Absolute temperature values and change to BL | Day 4 | 
| Assessment of defervescence | Absolute temperature values and change to BL | Day 7 | 
| Assessment of defervescence | Absolute temperature values and change to BL | Day 14 | 
| Assessment of defervescence | Absolute temperature values and change to BL | Day 28 | 
| Assessment of improvement or absence of coughing | Time to cough reported as mild oder non existent in days | Day 28 | 
| Assessment of improvement or absence of coughing | Time to non-existent coughing for all patients in days | Day 28 | 
| Assessment of improvement or absence of coughing - proportion of patients | proportion of patients with moderate or severe cough at BL who achieved cough reported as mild or none existent | Day 28 | 
| Assessment of improvement or absence of coughing - number of patients | Number of patients with moderate or severe cough at BL who achieved cough reported as mild or none existent | Day 28 | 
| Assessment of improvement or absence of coughing | proportion of patients who achieved cough reported as none existent | Day 28 | 
| Assessment of intensity and distribution of most bothersome symptom | Intensity of most bothersome symptom assessment done by visual analogue scale (VAS) and change to Baseline - score 0 to 10 cm, higher values describe higher intensity | Day 28 | 
| Assessment of intensity and distribution of most bothersome symptom | 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 | Day 28 | 
| Proportion of patients who return to usual health | proportion of patients who return to usual health | Day 28 | 
| Number of patients who return to usual health | Number of patients who return to usual health | Day 28 | 
| proportion of patients who return to usual activity | proportion of patients who return to usual activity | Day 28 | 
| Requirement of hospitalisation or oxygen supplementation | Number of patients requiring hospitalisation or oxygen supplementation (patient reported) | Day 28 | 
| Requirement of hospitalisation or oxygen supplementation | proportion of patients requiring hospitalisation or oxygen supplementation (patient reported) | Day 28 | 
| Disease progression/improvement | Number of patients with improved or progressed disease state (according to world health organisation (WHO) scale) - Score 0 - 10, higher score described more progressed state | Day 4 | 
| Disease progression/improvement | proportion of patients with improved or progressed disease state (according to world health organisation (WHO) scale) - Score 0 - 10, higher score described more progressed state | Day 4 | 
| Disease progression/improvement | Number of patients with improved or progressed disease state (according to world health organisation (WHO) scale) Score 0 - 10, higher score described more progressed state | Day 7 | 
| Disease progression/improvement | proportion of patients with improved or progressed disease state (according to world health organisation (WHO) scale) Score 0 - 10, higher score described more progressed state | Day 7 | 
| Disease progression/improvement | Number of patients with improved or progressed disease state (according to world health organisation (WHO) scale) Score 0 - 10, higher score described more progressed state | Day 14 | 
| Disease progression/improvement | proportion of patients with improved or progressed disease state (according to world health organisation (WHO) scale), Score 0 - 10, higher score described more progressed state | Day 14 | 
| Disease progression/improvement | Number of patients with improved or progressed disease state (according to world health organisation (WHO) scale) Score 0 - 10, higher score described more progressed state | Day 28 | 
| Disease progression/improvement | proportion of patients with improved or progressed disease state (according to world health organisation (WHO) scale) Score 0 - 10, higher score described more progressed state | Day 28 | 
| Disease progression/improvement | Number of patients with each WHO score Score 0 - 10, higher score described more progressed state | Day 4 | 
| Disease progression/improvement | proportion of patients with each WHO score Score 0 - 10, higher score described more progressed state | Day 4 | 
| Disease progression/improvement | Number of patients with each WHO score Score 0 - 10, higher score described more progressed state | Day 7 | 
| Disease progression/improvement | proportion of patients with each WHO score Score 0 - 10, higher score described more progressed state | Day 7 | 
| Disease progression/improvement | Number of patients with each WHO score Score 0 - 10, higher score described more progressed state | Day 14 | 
| Disease progression/improvement | proportion of patients with each WHO score Score 0 - 10, higher score described more progressed state | Day 14 | 
| Disease progression/improvement | Number of patients with each WHO score Score 0 - 10, higher score described more progressed state | Day 28 | 
| Disease progression/improvement | proportion of patients with each WHO score Score 0 - 10, higher score described more progressed state | Day 28 | 
| Disease progression/improvement | WHO score and change to BL Score 0 - 10, higher score described more progressed state | Day 4 | 
| Disease progression/improvement | WHO score and change to BL Score 0 - 10, higher score described more progressed state | Day 7 | 
| Disease progression/improvement | WHO score and change to BL Score 0 - 10, higher score described more progressed state | Day 14 | 
| Disease progression/improvement | WHO score and change to BL Score 0 - 10, higher score described more progressed state | Day 28 | 
| Disease progression/improvement | Number of patients in each disease severity state according to WHO score Score 0 - 10, higher score described more progressed state | Day 4 | 
| Disease progression/improvement | proportion of patients in each disease severity state according to WHO score Score 0 - 10, higher score described more progressed state | Day 4 | 
| Disease progression/improvement | Number of patients in each disease severity state according to WHO score Score 0 - 10, higher score described more progressed state | Day 7 | 
| Disease progression/improvement | proportion of patients in each disease severity state according to WHO score Score 0 - 10, higher score described more progressed state | Day 7 | 
| Disease progression/improvement | proportion of patients in each disease severity state according to WHO score Score 0 - 10, higher score described more progressed state | Day 14 | 
| Disease progression/improvement | Number of patients in each disease severity state according to WHO score Score 0 - 10, higher score described more progressed state | Day 14 | 
| Disease progression/improvement | proportion of patients in each disease severity state according to WHO score Score 0 - 10, higher score described more progressed state | Day 28 | 
| Disease progression/improvement | Number of patients in each disease severity state according to WHO score Score 0 - 10, higher score described more progressed state | Day 28 | 
| Assessment of oxygen saturation | Oxygen saturation measured by finger clip and change to BL | Day 4 | 
| Assessment of oxygen saturation | Oxygen saturation measured by finger clip and change to BL | Day 7 | 
| Assessment of oxygen saturation | Oxygen saturation measured by finger clip and change to BL | Day 14 | 
| Assessment of oxygen saturation | Oxygen saturation measured by finger clip and change to BL | Day 28 | 
| Assessment of intake of concomitant medication | Type and average daily dose of concomitant medication and total dose of paracetamol | Day 14 | 
| Assessment of intake of concomitant medication | Average days of additional intake of concomitant medication paracetamol | Day 4 | 
| Assessment of intake of concomitant medication | Average days of additional intake of concomitant medication paracetamol | Day 7 | 
| Assessment of intake of concomitant medication | Average days of additional intake of concomitant medication paracetamol | Day 14 | 
| Assessment of intake of concomitant medication | Average days of additional intake of concomitant medication paracetamol | Day 28 | 
| Assessment of intake of concomitant medication | Number of patients with a reduction in concomitant medication intake | Day 14 | 
| Assessment of intake of concomitant medication | proportion of patients with a reduction in concomitant medication intake | Day 14 | 
| Number of patients with hyposmia or anosmia | Number of patients with hyposmia or anosmia | Day 4 | 
| proportion of patients with hyposmia or anosmia | proportion of patients with hyposmia or anosmia | Day 4 | 
| Number of patients with hyposmia or anosmia | Number of patients with hyposmia or anosmia | Day 7 | 
| proportion of patients with hyposmia or anosmia | proportion of patients with hyposmia or anosmia | Day 7 | 
| Number of patients with hyposmia or anosmia | Number of patients with hyposmia or anosmia | Day 14 | 
| proportion of patients with hyposmia or anosmia | proportion of patients with hyposmia or anosmia | Day 14 | 
| Number of patients with hyposmia or anosmia | Number of patients with hyposmia or anosmia | Day 28 | 
| proportion of patients with hyposmia or anosmia | proportion of patients with hyposmia or anosmia | Day 28 | 
| Number of patients with fever | Number of patients with fever | Day 4 | 
| proportion of patients with fever | proportion of patients with fever | Day 4 | 
| Number of patients with fever | Number of patients with fever | Day 7 | 
| proportion of patients with fever | proportion of patients with fever | Day 7 | 
| Number of patients with fever | Number of patients with fever | Day 14 | 
| proportion of patients with fever | proportion of patients with fever | Day 14 | 
| Number of patients with fever | Number of patients with fever | Day 28 | 
| proportion of patients with fever | proportion of patients with fever | Day 28 | 
| Number of patients with COVID-19 vaccination | Number of patients with COVID-19 vaccination | Day 4 | 
| proportions of patients with COVID-19 vaccination | proportions of patients with COVID-19 vaccination | Day 4 | 
| Number of patients with COVID-19 vaccination | Number of patients with COVID-19 vaccination | Day 7 | 
| proportions of patients with COVID-19 vaccination | proportions of patients with COVID-19 vaccination | Day 7 | 
| Number of patients with COVID-19 vaccination | Number of patients with COVID-19 vaccination | Day 14 | 
| proportions of patients with COVID-19 vaccination | proportions of patients with COVID-19 vaccination | Day 14 | 
| Number of patients with COVID-19 vaccination | Number of patients with COVID-19 vaccination | Day 28 | 
| proportions of patients with COVID-19 vaccination | proportions of patients with COVID-19 vaccination | Day 28 | 
| Number of recovered COVID-19 patients | Number of recovered COVID-19 patients | Day 4 | 
| proportion of recovered COVID-19 patients | proportion of recovered COVID-19 patients | Day 4 | 
| Number of recovered COVID-19 patients | Number of recovered COVID-19 patients | Day 7 | 
| proportion of recovered COVID-19 patients | proportion of recovered COVID-19 patients | Day 7 | 
| Number of recovered COVID-19 patients | Number of recovered COVID-19 patients | Day 14 | 
| proportion of recovered COVID-19 patients | proportion of recovered COVID-19 patients | Day 14 | 
| Number of recovered COVID-19 patients | Number of recovered COVID-19 patients | Day 28 | 
| proportion of recovered COVID-19 patients | proportion of recovered COVID-19 patients | Day 28 | 
| Assessment of severe acute respiratory syndrome (SARS)- Corona virus (CoV) -2 negativity | Assessment of SARS-CoV-2 negativity measured by polymerase chain reaction (PCR) test) | Day 4 | 
| Assessment of SARS-CoV-2 negativity | Assessment of SARS-CoV-2 negativity measured by polymerase chain reaction (PCR) test) | Day 7 | 
| Assessment of SARS-CoV-2 negativity | Assessment of SARS-CoV-2 negativity measured by polymerase chain reaction (PCR) test) | Day 14 | 
| Assessment of SARS-CoV-2 negativity | Assessment of SARS-CoV-2 negativity measured by polymerase chain reaction (PCR) test) | Day 28 | 
| Assessment of compliance | Compliance to investigational medicinal product (IMP) by dose taken and as documented in patient diary | Day 4 | 
| Assessment of compliance | Compliance to IMP by dose taken and as documented in patient diary | Day 7 | 
| Assessment of compliance | Compliance to IMP by dose taken and as documented in patient diary | Day 14 | 
| Number of adverse events (AE) | Number of adverse events (AE) | through study completion, average 28 days | 
| Number of serious adverse events (SAE) | Number of serious adverse events (SAE) | through study completion, average 28 days | 
| Type and severity of adverse events | Type and severity of adverse events | through study completion, average 28 days | 
| Type and severity of serious adverse events | Type and severity of serious adverse events | through study completion, average 28 days | 
| Seriousness and relatedness of AEs | Seriousness and relatedness of AEs | through study completion, average 28 days | 
| Seriousness and relatedness of SAEs | Seriousness and relatedness of SAEs | through study completion, average 28 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ARDS, COVID 19, Bronchipret