Open Label Study to Compare Efficacy, Safety and Tolerability of Hydroxychloroquine Combined With Azithromycin Compared to Hydroxychloroquine Combined With Camostat Mesylate and to no Treatment in SARS CoV 2 Virus

Study Overview
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Brief Summary
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Patients with COVID-19 which are 60 years old or above or with comorbidities are at risk of deteriorating and developing severe illness. This prospective open label study will include people 60 years old or above or younger if at risk for severe disease. Individuals confirmed to have SARS-CoV-2 infection will be identified using medical records screening. They will then be offered to participate in the study and if agree will be given the informed consent. After examining inclusion and exclusion criteria they will be asked to sign the informed consent and after signing Information like immunizations, ECG results, diagnostic images and reports, written medical reports, diagnostic lab testing results (e.g. blood tests, urine tests, blood bank info), allergies and intolerances (drug and food allergies, food intolerances), prescription history, and general patient information (e.g. name, birthdate, personal health number, address, phone number) will be gathered. Those who are not eligible for the study will be informed of the reason(s) for ineligibility (generally it will be a safety exclusion and they should be aware of this). Those who are eligible will be randomized to one of three arms: hydroxychloroquine + azithromycin, hydroxychloroquine + camostat mesylate or doing nothing in a ratio of 2:1:2. Study drug will be dispensed by the hospital pharmacy. Follow up will continue for 8 weeks.

Detailed Description
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This prospective, open-label, placebo-controlled, randomized clinical trial will determine if hydroxychloroquine for 5 days plus camostat mesylate for 10 days, initiated in patients older than 60 years or younger but with risk factors for severe COVID 19 disease will reduce the risk of progression to severe COVID-19 disease compared to hydroxychloroquine plus azithromycin for 5 days or not treating with neither. Severe disease is defined as progression to invasive mechanical ventilation, reduced respiratory parameters (according to NEWS criteria) and 14 and 30-day mortality. This trial will enroll hospitalized consenting adults, who are age 18 or over, have a risk factor for severe disease, have no contraindication to treatment with hydroxychloroquine, can swallow pills, and who do not have severe underlying comorbidity where treatment is not likely to be beneficial to the patient. The primary outcome will be clinical state of the patient according to NEWS scoring on day 7. Secondary outcomes will be the proportion of participants requiring invasive mechanical ventilation, 14 and 30 -day mortality, and positive viral PCR at day 14. Randomization will be stratified by age and sex. Sheba medical center is a tertiary hospital affiliated to Tel Aviv University.

Official Title
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An Open-Label Study to Compare the Efficacy, Safety, and Tolerability of Hydroxychloroquine Combined With Azithromycin Compared to Hydroxychloroquine Combined With Camostat Mesylate and to no Treatment in Hospitalized Patients Suffering From a Mild or Moderate SARS CoV 2 Virus

Conditions
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COVID - 19

Intervention / Treatment
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* Drug: hydroxychloroquine in combination with camostat mesylate
* Drug: Hydroxychloroquine in combination of Azithromycin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 18 years and above COVID-19 confirmed by a real-time RT-PCR tests 7 days prior to clinical trial enrollment Mild disease (no pneumonia) with at least one of the following risk factors: Age > 55, prior lung or kidney disease, DM with HbA1c > 7.6%, hypertension, CVD, immuno - supressed, organ transplantation, HIV with a CD4 cell count of less than 250 cells/mm3, heavy smoking, BMI > 30. Moderate disease - pneumonia, Tachypnea > 24 BPM, tachicardia > 125 BPM, O2 saturation 93% or less Exclusion Criteria: Severe or critical disase Assisted ventilation Hospitalization in ICU Neutrophiles less than 2000 AST or ALT > 5 times normal QTc > 500 msec Pregnancy Treatment with a drug that prolongs QT

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 120 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: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: A - HCQ + AZT<br>Hydroxychloroquine 400 mg BID on day 1 and than 200 mg BID on days 2-5 + Azithromycin 500 mg QD on day 1 and 250 mg QD on days 2-5 | Drug: Hydroxychloroquine in combination of Azithromycin<br>* Hydroxychloroquine 400 mg BID on day 1 and than 200 mg BID on days 2-5 + Azithromycin 500 mg QD on day 1 and 250 mg QD on days 2-5<br>|
| Experimental: B - HCQ + CAM<br>Hydroxychloroquine 400 mg BID on day 1 and than 200 mg BID on days 2-5 + Camostat mesylat 200 mg TID for 10 days | Drug: hydroxychloroquine in combination with camostat mesylate<br>* Two drugs which may act as antivirals against SARS CoVid 2 (Hydroxychloroquine may also act as an immunomodulator, Camostat mesylate is a protease inhibitor)<br>|
| No Intervention: C - NI<br>No Intervention | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| clinical state as reflected by NEWS scoring | the clinical state of the patient regarding respiratory state as defined by the NEWS scoring system | 7 days | 
| positive PCR | positive PCR SARS COVID 2 in the respiratory system | 7 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| prevention of ICU | prevention of hospitaliztion in the ICU | 14 days | 
| prevention of assisted ventilation | prevention of assisted ventilation | 14 days | 
| prevention of ECMO | prevention of Extracorporeal Membrane Oxygenation (ECMO) | 14 days | 
| death | death | 14 days | 
| positive PCR | positive PCR SARS COVID 2 in the respiratory system | 14 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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COVID - 19, hydroxychloroquine, camostat mesylate