BromhexIne And Spironolactone For CoronаVirUs Infection Requiring HospiTalization

Study Overview
=================
Brief Summary
-----------------
Patients with mild and severe COVID 19 will be randomized 1:1 into two groups: experimental, which will get bromhexine and spironolactone, and control. Patients will get investigated therapy for ten days. Change in clinical assessment score COVID 19 (CAS COVID 19) between baseline and 12th day will be evaluated as a primary endpoint. Forty-five-day risk of death or mechanical ventilation will also be assessed.

Official Title
-----------------
Open Label Randomized Clinical Trial BromhexIne And Spironolactone For CoronаVirUs Infection Requiring HospiTalization

Conditions
-----------------
COVID 19

Intervention / Treatment
-----------------
* Drug: Bromhexine and Spironolactone
* Drug: Base therapy


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: signed inform consent COVID 19 with the mild and severe course. The diagnosis could be made with positive polymerase chain reaction (PCR) (International Statistical Classification (ICD-10) code - U07.1) and/or virus pneumonia in computer tomography (ICD 10 code - U07.2) 5. Lung exposure on CT more than 25% 6. Sp02 without supportive oxygen ≤ 93% 7. C-reactive protein > 60 mg/l or elevation of C reactive protein 3 times in 8-14 days after first symptoms Exclusion Criteria: pregnancy and breastfeeding hypersensitivity to Spironolactone hypersensitivity to Bromhexine Known liver failure Glomerular filtration rate <20 ml/ min physician judgment that the patient will need mechanical ventilation in 24 hours other indications for Spironolactone Active cancer

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Bromhexine And Spironolactone<br> | Drug: Bromhexine and Spironolactone<br>* Bromhexine 8 mg x 4 times a day x 10 days Spironolactone 50 mg x once a day x 10 days<br>|
| Active Comparator: Base therapy<br> | Drug: Base therapy<br>* Therapy currently recommended by Ministry of Health of Russian Federation for COVID 19 treatment<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in clinical assessment score COVID 19 (CAS COVID 19) | change in CAS COVID 19 between baseline and 12th +/- 2 days CAS COVID 19 measures clinical and laboratory parameters in 7 domains: respiratory rate (< 18 - 0 point; 18-22 - 1 point; 23-26 - 2 point; >26 - 3 point) body temperature (35.5 - 37.0 - 0 point; < 35.5 - 1 point; 37.1 - 38.5 - 1 point; > 38.5 - 2 point) Sp02 without support oxygen (> 93% - 0 point; 90-93% - 1 point; < 90% - 2 point) ventilation (not required - 0 point; low-flow ventilation - 1 point; Non-invasive positive pressure ventilation - 2 point; mechanical ventilation - 3 point) C-reactive protein (> 10 - 0 point; 10-59 - 1 point; 60-120 - 2 point; > 120 - 3 point) d - dimer (< 0.51 - 0 point; 0.51 - 2.0 - 1 point; 2.01 - 5.0 - 2, > 5.0 - 3 point) exposure area on lung CT (no pneumonia - 0; 1-24% - 1 point; 25-50% - 2; 51-75% - 3, > 75% - 4). Minimal number of points - 0; max - 20.Lower the score-better health | baseline, day 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| - Combine endpoint - | time to death or mechanical ventilation | 12 days, 45 days | 
| C-reactive protein | - Change from baseline in C-reactive protein | 12 days, 45 days | 
| D-dimer | - Change from baseline in D-dimer | 12 days, 45 days | 
| EuroQol Group. EQ-5D™ | Change from baseline in EQ-5D. The EQ-5D descriptive system comprises the 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 3 levels: no problems, some problems, and extreme problems. The patient is asked to indicate his/her health state by ticking the box to the most appropriate statement. This decision results into a 1-digit number, . The digits for the five dimensions can be combined into a 5-digit number that describes the patient's health state. | 12 days, 45 days | 
| EuroQol Group. EQ VAS | Change from baseline in EQ VAS EQ VAS records the patient's self-rated health on a vertical visual analogue scale where the endpoints are labelled 'Best imaginable health state' and 'Worst imaginable health state'. The VAS can be used as a quantitative measure of health outcome by patient's own judgement. | 12 days, 45 days | 
| HADS | - Change from baseline Hospital Anxiety and Depression Scale/The Hospital Anxiety and Depression Scale (HADS) is a 14-item measure designed to assess anxiety and depression symptoms in medical patients, with emphasis on reducing the impact of physical illness on the total score. Items are rated on a 4-point severity scale. The HADS produces two scales, one for anxiety (HADS-A) and one for depression (HADS-D), differentiating the two states. Scores of greater than or equal to 11 on either scale indicate a definitive case | 14 days, 45 days | 
| Hospital length of stay | Time from admission to the hospital to discharge form the hospital | up to 45 days | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
COVID 19, bromhexine, spironolactone