Cardiovascular Events, MACE
Conditions
Keywords
post Marketing Requirements (PMR) study, cardiovascular events, non-fatal myocardial infarction, non-fatal stroke, cardiovascular death, arrythmias, coronary artery disease, heart failure, myocardial disorders
Brief summary
The aim of this study is to evaluate the risk of serious adverse cardiovascular events in adolescent and adult patients with severe asthma taking tezepelumab compared to a population receiving standard of care treatment for severe asthma.
Detailed description
Tezepelumab (brand name: TEZSPIRE®), a human monoclonal antibody specific for the epithelial cell-derived cytokine thymic stromal lymphopoietin (TSLP), was recently launched as a first-in-class biologic add on treatment for patients with severe asthma. Results from DESTINATION, a long-term extension, phase 3 trial, showed a numeric imbalance in the occurrence of cardiac disorder system organ class serious adverse events (SAEs) in participants receiving tezepelumab compared to placebo. The observed imbalance resulted in the inclusion of serious cardiovascular events as an important potential risk to be addressed in the European Union (EU) risk management plan (RMP). AstraZeneca proposed to evaluate the risk of serious cardiovascular events with long-term tezepelumab treatment to meet regulatory requirements under a category 3 Post-Authorisation Safety Study (PASS). This study is a non-interventional, longitudinal, population-based cohort study, using secondary data derived from multiple data sources. The study will consist of descriptive and a prevalent new-user design for comparative analyses of serious cardiovascular events outcomes in adolescent and adult patients with severe asthma exposed and unexposed to tezepelumab. The study will be conducted using data sources from Denmark, France, Germany, and the United States of America (USA). The start of the study period will correspond to tezepelumab market launch date in each country of interest (i.e. between Q1 2022 - Q3 2023). An approximately five-year study period is planned in each country, with an anticipated last date of study period on 28 February 2029.
Interventions
DRUGTezepelumab
The exposure of primary interest is tezepelumab for severe asthma. Exposure will be assessed based on prescriptions or administrations depending on the data source. A comparable cohort of unexposed patients treated with high-intensity SOC will be identified based on the presence of a trigger exposure (i.e., augmentation or change of the non-biologic high-intensity treatment that does not represent treatment de-escalation) to mirror tezepelumab start in the exposed cohort. Due to the limited knowledge of the cardiovascular profile of biologics, SOC for comparative analyses will only include non-biologic high-intensity treatment.
Sponsors
AstraZeneca
IQVIA Pvt. Ltd
Study design
Observational model
COHORT
Time perspective
RETROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
12 Years to 130 Years
Healthy volunteers
No
Inclusion criteria
* patients with a diagnosis of asthma receiving tezepelumab or high-intensity SOC treatment for severe asthma at any point during the study inclusion period.
Exclusion criteria
for both exposed and unexposed groups include: * \<12 months of data availability prior to index date, * age \<12 years at index date, * history of congenital heart disease or heart transplant outcome-specific exclusion criterion applied for each objective will include the presence of non-fatal myocardial infarction or stroke and the specific outcome of interest in the 180 days prior to index date * for comparative analysis, an additional exclusion criterion will be considered, i.e. exposure to non-tezepelumab biologics on index date or within the 5-half-life clearance period of the biologic * matching criteria (including, among other variables, the type and duration of SOC exposure in the 12 months before index date and propensity score \[PS\] matching) will be applied to ensure exposed and unexposed patients' comparability
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| composite outcome MACE | five years from tezepelumab market launch | The primary outcome of interest is the composite outcome MACE, consisting of non-fatal myocardial infarction, non-fatal stroke, or cardiovascular death. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| composite of four serious adverse cardiovascular events | five years from tezepelumab market launch | The secondary outcomes of interest are a composite of four serious adverse cardiovascular events, including arrhythmias, coronary artery disease, heart failure and myocardial disorders, and the individual components of the primary and secondary composite outcomes. |
Countries
Denmark, France, Germany, United States
Contacts
CONTACTAstraZeneca Clinical Study Information Center
PRINCIPAL_INVESTIGATORPeter Egger
IQVIA Pty Ltd
Outcome results
None listed