Clinical trial NCT04355052: 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
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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: COVID - 19
Keywords: COVID - 19
hydroxychloroquine
camostat mesylate
Lead sponsor: Sheba Medical Center
Sponsor class: OTHER_GOV
First posted: 2020-04-21
Enrollment: 250
Sex: ALL
Minimum age (years): 18
Maximum age (years): 120
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: clinical state as reflected by NEWS scoring
timeFrame: 7 days
measure: positive PCR
timeFrame: 7 days
Secondary outcomes:
measure: prevention of ICU
timeFrame: 14 days
measure: prevention of assisted ventilation
timeFrame: 14 days
measure: prevention of ECMO
timeFrame: 14 days
measure: death
timeFrame: 14 days
measure: positive PCR
timeFrame: 14 days
Other outcomes:
measure: death
timeFrame: 60 days
Locations:
city: Ramat Gan
country: Israel
facility: Sheba Medical Center
city: Tel HaShomer
country: Israel
facility: Sheba Medical Center
Study officials:
References: