MedPath

Tezspire Cardiac Events PASS

Not yet recruiting
Conditions
Cardiovascular Events
MACE
Interventions
Registration Number
NCT06951867
Lead Sponsor
AstraZeneca
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.

Recruitment & Eligibility

Status
NOT_YET_RECRUITING
Sex
All
Target Recruitment
95574
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
Exclusion Criteria

Not provided

Study & Design

Study Type
OBSERVATIONAL
Study Design
Not specified
Arm && Interventions
GroupInterventionDescription
tezepelumab exposed pregnanciesTezepelumabpatients with a diagnosis of severe asthma receiving tezepelumab
Primary Outcome Measures
NameTimeMethod
composite outcome MACEfive 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 Outcome Measures
NameTimeMethod
composite of four serious adverse cardiovascular eventsfive 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.

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