A prospective controlled proof-of-concept trial to demonstrate anti-viral effects of oral bromelaine in COVID-19 positive patients

INTERVENTION: Trade Name: Bromelaintabletten hysan, 500 F.I.P.‐Einheiten, magensaftresistente Tabletten Pharmaceutical Form: Gastro‐resistant tablet INN or Proposed INN: Bromelains CAS Number: 9001‐00‐7 Current Sponsor code: Bromelain Other descriptive name: Bromelaina Concentration unit: U unit(s) Concentration type: equal Concentration number: 500‐ Pharmaceutical form of the placebo: Gastro‐resistant tablet Route of administration of the placebo: Oral use CONDITION: Diagnosis of SARS‐CoV‐2 infection documented by a positive PCR test ; MedDRA version: 23.1 Level: PT Classification code 10084460 Term: COVID‐19 treatment System Organ Class: 10042613 ‐ Surgical and medical procedures Therapeutic area: Diseases [C] ‐ Virus Diseases [C02] PRIMARY OUTCOME: Main Objective: The primary objective of the treatment with Bromelain tablets in COVID‐19 positive patients is to assess the change in Patient reported symptoms. Primary end point(s): Primary endpoint of the efficacy of Bromelain tablets in COVID‐positive patients is the baseline‐adjusted course of the median of Symptoms (anosmia, ageusia, fever, cough, sore throat, shortness of breath, coryza, general weakness, headache, aching limbs, loss of appetite, pneumonia, nausea, abdominal pain, vomiting, diarrhoea, conjunctivitis, rash, lymph node swelling, apathy, somnolence) documented over the course of the study (day 1 ‐ day 11).; Secondary Objective: Secondary objectives of the Trial are: ; ‐ to assess the Clinical improvement of the Patient Status via a WHO ordinal scale; ‐ to assess the Clinical improvement of the Patient state via measurement of Body temperature and blood Oxygen Saturation; ‐ to assess the Clinical improvement of the Patient state via measurement of blood Parameters; ‐ to assess the Clinical improvement of the Patient state via measurement of Virus load in nasopharyngeal swabs (Ct values) ; ‐ to assess the clincal Impact of the Treatment with Bromelain tablets with regards to Quality of Life Timepoint(s) of evaluation of this end point: COVID‐19 symptom severity will be assessed daily (day 1 to day 11). SECONDARY OUTCOME: Secondary end point(s): 1. baseline‐adjusted area under the curve of the total symptom score ; 2. baseline‐adjusted area under the curve of each individual symptom ; 3. proportion of patients who show a decrease in their baseline‐adjusted symptoms score of SARS‐CoV‐2 within 3 days of treatment ; 4. change in patient status via measurement of virus load in nasopharyngeal swabs (Ct value at baseline D1 vs. Ct‐values at D4, D7 and D11). ; 5. proportion of patients with the presence of a positive PCR‐test at day 11 (virus load in nasopharyngeal swabs) ; 6. change in patient status using a 11‐category ordinal score as proposed by the WHO ; 7. baseline‐adjusted change in patient status by measurement of temperature (fever) and oxygen saturation of the blood ; 8. baseline‐adjusted Change in patient status via measurement of blood parameters ; 9. baseline‐adjusted change in quality of life as assessed by the SF‐36 generic quality of life questionnaire. ; 10. Treatment emergent adverse Events and adverse drug reactions Timepoint(s) of evaluation of this end point: 1) baseline‐adjusted area under the curve (day 1 ‐ day 11) ; 2) baseline‐adjusted area under the curve (day 1 ‐ day 11) ; 3) day 4 ; 4) day 1, day 4, day 7, day 11 ; 5) day 11 ; 6) day 1, day 4, day 7, day 11, day 60 ; 7) day 1, day 4, day 7, day 11 ; 8) day 1, day 4, day 7, day 11 ; 9) day 1, day 4, day 7, day 11 ; 10) over the entire study period (day 1 ‐ day 60) ; ; INCLUSION CRITERIA: Patients must meet all of the following inclusion criteria in order to participate in this study: ‐ Legally competent patients who are personally capable of giving informed consent and to sign and date the Consent Form prior to any trial related activity, ‐ Patients aged from 18 ‐ 60 years ‐ Having the diagnosis of SARS‐CoV‐2 infection documented by a positive PCR test ‐ Patients showing at least one of the typical symptoms for COVID‐19 disease, such as fever, shortness of breath, cough, anosmia (loss of odor), or ageusia (loss of taste). ‐ Enrolment should generally done on the day of availability of positive COVID‐19 PCR test result, and on the subsequent day. The interval between sample collection and enrolment should generally not exceed 48 hours. ‐ For females: non‐pregnant, non‐lactating with adequate contraception*, until D16 or females unable to bear children (i.e., tubal ligation, hysterectomy, or post‐menopausal (de