eVusheld Assessment reaL wORld Effectiveness in Israel Clalit Health Services

Study Overview
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Brief Summary
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An AstraZeneca-sponsored observational, electronic healthcare record (EHR)-embedded retrospective cohort study to assess the real-world effectiveness of EVUSHELD against SARS-CoV-2 infection, COVID-19-related hospitalization, and other COVID-19 related outcomes in the total EVUSHELD eligible patient population in the Clalit Health Services in Israel.

Detailed Description
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This a Phase IV observational, secondary data study to assess the effectiveness of EVUSHELD in preventing COVID-19 infection and severe outcomes using the electronic medical records from the nationwide integrated health system. The study is designed as an AstraZeneca-sponsored observational, electronic healthcare record (EHR)-embedded retrospective cohort study to assess the real-world effectiveness of EVUSHELD against SARS-CoV-2 infection, COVID-19-related hospitalization, and other COVID-19 related outcomes in the total EVUSHELD eligible patient population in the Clalit Health Services in Israel.

Official Title
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An Observational Study to Assess the Real-world Effectiveness of EVUSHELD™ (Tixagevimab/Cilgavimab) as Pre-exposure Prophylaxis Against COVID-19 Among Immunocompromised Patients in Israel

Conditions
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SARS-CoV-2, COVID-19

Intervention / Treatment
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* Drug: EVUSHELD


Participation Criteria
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Eligibility Criteria
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Individuals who meet all criteria below will be included. The eligibility criteria aligns with the guidelines of the Israeli Ministry of Health Inclusion criteria: Aged 12 years and older as of the date of receipt of EVUSHELD No record of infection or SARS-CoV- hospitalization within last 90 days prior to the index date Individuals who are moderate/severe immune compromised due to a medical condition or receipt of immunosuppressive medications or treatments and may mount an adequate immune response to COVID-19 vaccine: Hypogammaglobinemia patients regularly treated with immunoglobulins Patients treated with B-cell depleting therapy, including for example such anti-CD20 as rituximab, obinatuzumab, ofatumumab, veltuzumab, Y-ibritumomab tiuxetan or ocrelizumab, even without malignant disease, up to six months from treatment. Patients that are treated with B-cell depleting therapy (i.e. anti CD20, rituximab, Y-ibritumomab tiuxetan, veltuzumab, ofatumumab, obinatuzumab, ocrelizumab), without a malignant disease Bone marrow transplant (up to a year from the BMT) from outside donors, or with GVHD grades 3-4. Bone marrow transplant (up to a 6 months after the BMT) from self Patients after (CAR) T-cell therapy (chimeric antigen receptor T-cell therapy) up to 6 months from the treatment. Lungs transplant recipients Solid organ transplant recipients (who has any kind of transplant) or those who received ATG (anti thymocyte globulin) over the last 6 months Patients with aggressive lymphoma. Multiple Myeloma patients that have active disease, and on treatment at the time of study initiation. Individuals who meet the criterion below will be excluded: Per the current FDA EUA, individuals currently infected with SARS-CoV-2 are not eligible for EVUSHELD as PrEP. Therefore, in the main analysis, individuals who meet the following criteria will also be excluded. Exclusion Criteria: With evidence of COVID 19 (i.e., a positive diagnostic test, or COVID-19 diagnosis code) in the period of 90 days before (pseudo) index date OR With evidence of SARS-CoV-2 infection on the (pseudo) index date or anytime within the 6-day period immediately following this date (i.e., index date to index date+6)
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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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| EVUSHELD Arm<br>Individuals given EVUSHELD for pre-exposure prophylaxis | Drug: EVUSHELD<br>* EVUSHELD (AZD 7442, Tixagévimab/Cilgavimab)<br>|
| Concurrent Control Arm<br>Individuals eligible for EVUSHELD pre-exposure prophylaxis but did not receive Evusheld | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hospitalisation due to COVID-19 | Any record of admission to hospital that was reported to the Israeli MOH as hospitalization due to SARS-CoV-2 | up to 6 months | 
| All-cause mortality | All-cause deaths reported in the patient's record | up to 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Documented SARS-CoV-2 Infection, COVID-19 related mortality, Severe COVID-19 | SARS-CoV-2 diagnostic test (eg, PCR, nucleic acid amplification, antigen) OR medical encounter resulting in a diagnosis code for COVID-19b OR medical encounter resulting in a code for isolation due to COVID-19 | 6 months and 12 months | 
| COVID-19 mortality | Any record indicating death due to COVID-19 or record of death certificate mentioning SARS-CoV-2 as cause of death. | 6 months and 12 months | 
| COVID-19-related healthcare resource utilization (HCRU) | Any record of COVID-19 hospitalisation, ICU admission, mechanical ventilation and prescriptions of therapies for COVID-19 | 6 months | 
| COVID-19-related healthcare resource utilization | Any record of hospital admission including hospital lenght of stay, ICU, mechanical ventilation, prescription/dispensations of antiviral drugs used for COVID-19 drugs | 6 months | 
| SAEs/AESIs | Any record of Serious Adverse Events (SAEs) or Adverse Events of Special Interests (AESIs) up to 6 months following initiation of Evusheld | 6 months | 
| Adverse events (AEs) | Any record of Adverse events up to 12 months following initiation of Evusheld | 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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SARS-CoV-2, COVID-19, Immunocompromised Patients, Pre-exposure Prophylaxis Against COVID-19, Evusheld