BromhexIne And Spironolactone For CoronаVirUs Infection Requiring HospiTalization (BISCUIT)

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

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.

Study Overview

• Status: Unknown
• Conditions: COVID 19
• Intervention / Treatment: Drug: Bromhexine and Spironolactone; Drug: Base therapy

• Study Type: Interventional
• Enrollment (Anticipated): 80
• Phase: Phase 3

Contacts and Locations

Study Locations

• Russian Federation
  • Moscow Region
    • Moscow, Moscow Region, Russian Federation, 119620
      • Recruiting
      • Lomonosov Moscow State University Medical Research and Educational Center
      • Contact: Julia Begrambekova, Phd; Phone Number: +79854679273; Email: begrambekova@ossn.ru
      • Contact: Yana Orlova, Professor; Phone Number: +791651663002; Email: yaorlova@mc.msu.ru

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

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

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

Collaborators and Investigators

• Sponsor: Lomonosov Moscow State University Medical Research and Educational Center

Study record dates

Study Major Dates

• Study Start (Actual): May 16, 2020
• Primary Completion (Anticipated): July 18, 2020
• Study Completion (Anticipated): August 23, 2020

Study Registration Dates

• First Submitted: May 27, 2020
• First Submitted That Met QC Criteria: June 7, 2020
• First Posted (Actual): June 9, 2020

Study Record Updates

• Last Update Posted (Actual): June 9, 2020
• Last Update Submitted That Met QC Criteria: June 7, 2020
• Last Verified: June 1, 2020

More Information

Terms related to this study

• Keywords: COVID 19; spironolactone; bromhexine
• Additional Relevant MeSH Terms: Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19; Coronavirus Infections; Physiological Effects of Drugs; Hormones, Hormone Substitutes, and Hormone Antagonists; Natriuretic Agents; Diuretics; Respiratory System Agents; Hormone Antagonists; Mineralocorticoid Receptor Antagonists; Diuretics, Potassium Sparing; Expectorants; Spironolactone; Bromhexine
• Other Study ID Numbers: MSU160520

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Sharing Time Frame: After publishing
• IPD Sharing Access Criteria: any application for access the data will be evaluated by ethical commite of LOMONOSOV MOSCOW STATE UNIVERSITY MEDICAL RESEARCH AND EDUCATIONAL CENTER
• IPD Sharing Supporting Information Type: Study Protocol; Informed Consent Form (ICF); Clinical Study Report (CSR); Analytic Code

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No