Design and rationale of DemonsTTRate: a global, long-term observational study to evaluate vutrisiran in patients with transthyretin amyloidosis with cardiomyopathy
P Garcia-Pavia, R Khedraki, Y Matsue, R Pfister, D Yaranov, S Bender, E S Brouwer, V Menon, K Verhulst, Z ShahAbstract
Background/Introduction
Transthyretin amyloidosis with cardiomyopathy (ATTR-CM) is a progressive, fatal disease caused by amyloid deposits in the heart. In the HELIOS-B trial, RNA interference with vutrisiran significantly reduced the risk of all-cause mortality and recurrent cardiovascular events while preserving functional capacity and quality of life vs placebo in patients with ATTR-CM. These benefits were maintained in the 1-year open-label extension. Real-world data can further enhance the understanding of ATTR-CM treatment patterns and assess outcomes with vutrisiran in clinical practice.
Purpose
To describe the rationale and design of DemonsTTRate, a global, prospective, long-term, observational study to assess vutrisiran use in real-world healthcare management of patients treated for ATTR-CM.
Methods
DemonsTTRate will enrol ≥2000 adult patients with ATTR-CM who are initiating treatment with vutrisiran or another approved ATTR-CM therapy (who have never received vutrisiran) in a real-world setting. Patients enrolled in interventional clinical trials will be excluded. Data will be collected by physicians at enrolment, at each routine visit and at least every 6 months. Patient-reported outcomes (PROs) will be collected directly from patients at enrolment and every 6 months thereafter. Data will be collected on patient demographics and disease characteristics, other relevant medical history, PROs, imaging, ATTR-CM and heart failure treatments, laboratory tests, healthcare resource use and vital status. Patients will be followed for up to 5 years, or until patient withdrawal of consent, loss to follow-up, death or the end of the study, whichever occurs first. Study results will be mainly descriptive. Time-to-event analyses will be performed for relevant outcomes.
Results
The study was initiated in November 2025 at cardiac amyloidosis treatment sites in the US, Germany and Japan. Additional countries will be included as access to vutrisiran for the ATTR-CM indication expands. Full details of the study design will be presented.
Conclusion
The real-world DemonsTTRate study will examine the clinical characteristics and treatment patterns of patients with ATTR-CM treated with vutrisiran over 5 years. It will also assess their health-related quality of life and healthcare resource utilisation. Additionally, the study will generate robust real-world evidence on long-term outcomes with vutrisiran compared to other ATTR-CM treatments in routine clinical practice.