Tezspire Cardiac Events PASS (TRESPASS)

An Observational Multi-Country Post-Authorisation Safety Study to Evaluate the Risk of Serious Adverse Cardiovascular Events in Adolescent and Adult Patients With Severe Asthma Taking Tezepelumab

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.

Study Overview

• Status: Recruiting
• Conditions: Cardiovascular Events; MACE
• Intervention / Treatment: Drug: Tezepelumab

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.

• Study Type: Observational
• Enrollment (Estimated): 16640

Contacts and Locations

• Study Contact: Name: AstraZeneca Clinical Study Information Center; Phone Number: 1-877-240-9479; Email: information.center@astrazeneca.com

Study Locations

• Denmark
  • Copenhagen, Denmark
    • Recruiting
    • Danish registries (access/analysis)
    • Contact: Email: kontakt@sundhedsdata.dk
• France
  • Paris, France
    • Recruiting
    • French National Health Data System (SNDS)
    • Contact: Email: regis.lassalle@health-data-hub.fr
• Germany
  • Berlin, Germany
    • Recruiting
    • Team Gesundheit GKV Claims data (SHI)
    • Contact: Email: friedel@teamgesundheit.de
• United States
  • Delaware
    • Wilmington, Delaware, United States, 19801
      • Recruiting
      • Healthcare Integrated Research Database (HIRD)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

The study will be conducted using data sources from Denmark, France, Germany, and the United States of America (USA).

The source population will consist of patients with a diagnosis of asthma receiving tezepelumab or high-intensity SOC treatment for severe asthma at any point during the study inclusion period. From this source population, the exposed study population (i.e. patients who initiate tezepelumab treatment) and the unexposed study population (i.e. comparable patients who are unexposed to tezepelumab) will be identified.

Description

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

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
tezepelumab severe asthma patients; patients with a diagnosis of severe asthma receiving tezepelumab	Drug: Tezepelumab; 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.; Other Names: TEZSPIRE
tezepelumab unexposed asthma patients; patients with a diagnosis of severe asthma receiving non-tezepelumab standard of care for severe asthma

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
composite outcome MACE	The primary outcome of interest is the composite outcome MACE, consisting of non-fatal myocardial infarction, non-fatal stroke, or cardiovascular death.	five years from tezepelumab market launch

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
composite of four serious adverse cardiovascular events	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.	five years from tezepelumab market launch

Collaborators and Investigators

• Sponsor: AstraZeneca
• Collaborators: IQVIA Pvt. Ltd
• Investigators: Principal Investigator: Peter Egger, IQVIA Pty Ltd

Study record dates

Study Major Dates

• Study Start (Actual): September 15, 2025
• Primary Completion (Estimated): May 31, 2029
• Study Completion (Estimated): May 31, 2029

Study Registration Dates

• First Submitted: April 23, 2025
• First Submitted That Met QC Criteria: April 23, 2025
• First Posted (Actual): April 30, 2025

Study Record Updates

• Last Update Posted (Actual): May 11, 2026
• Last Update Submitted That Met QC Criteria: May 8, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: coronary artery disease; cardiovascular events; heart failure; cardiovascular death; non-fatal stroke; arrythmias; post Marketing Requirements (PMR) study; non-fatal myocardial infarction; myocardial disorders
• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Heart Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Coronary Disease; Myocardial Ischemia; Heart Failure; Coronary Artery Disease; tezepelumab
• Other Study ID Numbers: D5180R00024

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal Vivli.org. All requests will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. "Yes", indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.
• IPD Sharing Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA PhRMA Data Sharing Principles. For details of our timelines, please refer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• IPD Sharing Access Criteria: When a request has been approved, AstraZeneca will provide access to the anonymized individual patient-level data via secure research environment Vivli.org. A signed Data Usage Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No