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

NCT ID: NCT04355052

Last Updated: 2020-04-21

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE3
• Total Enrollment: 250 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-04-11
• Study Completion Date: 2020-12-11

Brief Summary

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

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.

Conditions

COVID - 19

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

A - HCQ + AZT

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

Group Type: ACTIVE_COMPARATOR

Hydroxychloroquine in combination of Azithromycin

Intervention Type: DRUG

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

B - HCQ + CAM

Hydroxychloroquine 400 mg BID on day 1 and than 200 mg BID on days 2-5 + Camostat mesylat 200 mg TID for 10 days

Group Type: EXPERIMENTAL

hydroxychloroquine in combination with camostat mesylate

Intervention Type: DRUG

Two drugs which may act as antivirals against SARS CoVid 2 (Hydroxychloroquine may also act as an immunomodulator, Camostat mesylate is a protease inhibitor)

C - NI

No Intervention

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

hydroxychloroquine in combination with camostat mesylate

Two drugs which may act as antivirals against SARS CoVid 2 (Hydroxychloroquine may also act as an immunomodulator, Camostat mesylate is a protease inhibitor)

Intervention Type: DRUG

Hydroxychloroquine in combination of Azithromycin

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

Intervention Type: DRUG

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 120 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Sheba Medical Center

OTHER_GOV

Sponsor Role: lead

Responsible Party

Itsik Levy Dr

Infectious Disease specialist

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Sheba Medical Center

Ramat Gan, , Israel

Site Status: RECRUITING

Sheba Medical Center

Tel Litwinsky, , Israel

Site Status: RECRUITING

Countries

Israel

Facility Contacts

Itzchak Levy, MD

Role: primary

itsik.levi@sheba.health.gov.il

97235304937

Irit Avisar, RN

Role: backup

irit.avisar@sheba.health.gov.il

97235304937

Itzchak Levy, MD

Role: primary

itsik.levy@sheba.health.gov.il

0526667525

Other Identifiers

7092-20-SMC

Identifier Type: -

Identifier Source: org_study_id