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

COVID - 19 Clinical Trial

— COSTA  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04355052
• Other study ID #: 7092-20-SMC
• Status: Recruiting
• Phase: Phase 3
• Start date: April 11, 2020
• Est. completion date: December 11, 2020

Study information

• Verified date: April 2020
• Source: Sheba Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 250
• Est. completion date: December 11, 2020
• Est. primary completion date: October 11, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 120 Years

Eligibility

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

Related Conditions & MeSH terms

• COVID - 19

Intervention

Drug:
• 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)
• 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

Locations

Country	Name	City	State
Israel	Sheba Medical Center	Ramat Gan
Israel	Sheba Medical Center	Tel HaShomer

Sponsors (1)

Lead Sponsor	Collaborator
Sheba Medical Center

Country where clinical trial is conducted

Israel, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	death	death	60 days
Primary	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
Primary	positive PCR	positive PCR SARS COVID 2 in the respiratory system	7 days
Secondary	prevention of ICU	prevention of hospitaliztion in the ICU	14 days
Secondary	prevention of assisted ventilation	prevention of assisted ventilation	14 days
Secondary	prevention of ECMO	prevention of Extracorporeal Membrane Oxygenation (ECMO)	14 days
Secondary	death	death	14 days
Secondary	positive PCR	positive PCR SARS COVID 2 in the respiratory system	14 days