OverTTuRe: Characteristics, Treatment Patterns and Outcomes of Patients With ATTR Amyloidosis (OverTTuRe)

OverTTuRe: An Observational Multi-Country Study Collecting Real-World Secondary Data on the Characteristics, Treatment Patterns and Outcomes of Patients With ATTR Amyloidosis

The overall aim of this observational study is to generate real-world evidence on the pre- and post-diagnosis disease journeys, including baseline characteristics, treatment patterns and selected clinical, economic, and humanistic outcomes (for example Health Related Quality of Life (HRQoL), Neuropathy impairment score, activities of daily living (ADL) assessments) in patients with ATTR amyloidosis, and to better understand how the disease is presented.

Study Overview

• Status: Recruiting
• Conditions: ATTR Amyloidosis
• Intervention / Treatment: Other: no intervention

Detailed Description

This retrospective, observational, longitudinal, multi-country cohort study aims to describe characteristics, treatment patterns, and outcomes in ATTR amyloidosis patients.

Primary objectives: Describe patient characteristics (for example demographics, family history of ATTR, key comorbidities and humanistic outcomes (e.g. Health Related Quality of Life (HRQoL), Neuropathy impairment score, activities of daily living (ADL) assessments), treatment patterns, and disease outcomes. Characterize and quantify the healthcare resource utilization (HCRU) in ATTR amyloidosis patients who will be followed post-index until the end of follow-up.

Secondary objectives: Describe demographics, clinical characteristics and HCRU in ATTR amyloidosis patients prior to diagnosis.

• Study Type: Observational
• Enrollment (Estimated): 52121

Contacts and Locations

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

Study Locations

• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2P 4K7
      • Recruiting
      • Research Site
• China
  • Beijing, China
    • Completed
    • Research Site
  • Changsha, China
    • Completed
    • Research Site
  • Chengdu, China
    • Completed
    • Research Site
  • Guangzhou, China
    • Completed
    • Research Site
  • Wuhan, China
    • Completed
    • Research Site
• Denmark
  • Horsens, Denmark
    • Completed
    • Research Site
• Germany
  • Berlin, Germany
    • Completed
    • Research Site
• Japan
  • Tokyo, Japan
    • Completed
    • Research Site
• Portugal
  • Lisbon, Portugal
    • Recruiting
    • Research Site
  • Porto, Portugal
    • Not yet recruiting
    • Research Site
• Spain
  • A Coruña, Spain
    • Completed
    • Research Site
  • Barcelona, Spain
    • Completed
    • Research Site
  • Bilbao, Spain
    • Completed
    • Research Site
  • El Palmar, Spain
    • Completed
    • Research Site
  • Huelva, Spain
    • Completed
    • Research Site
  • Las Palmas de Gran Canaria, Spain
    • Completed
    • Research Site
  • Madrid, Spain
    • Completed
    • Research Site
  • Majadahonda, Spain
    • Completed
    • Research Site
  • Palma de Mallorca, Spain
    • Completed
    • Research Site
  • Salamanca, Spain
    • Completed
    • Research Site
  • Valencia, Spain
    • Completed
    • Research Site
• Sweden
  • Södertälje, Sweden
    • Completed
    • Research Site
  • Umeå, Sweden
    • Completed
    • Research Site
• United Kingdom
  • London, United Kingdom
    • Completed
    • Research Site
• United States
  • Minnesota
    • Eden Prairie, Minnesota, United States, 55344
      • Completed
      • Research Site

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Non-Probability Sample

Study Population

This study will include data from patients aged > 18 years with a diagnosis of ATTR amyloidosis or other evidence confirming ATTR amyloidosis. Patients will be followed until exit from the database (loss to follow-up), death, or end of database period (data collection). Baseline data will apply a lookback period of 12 months. Patient identification will be from 2014-01-01 onwards

Description

Inclusion Criteria:

• Patients aged >18 years at study index date AND
• A reported diagnosis code for amyloidosis OR
• A claim for ATTR-specific treatment OR
• A positive biopsy for amyloidosis and positive immunostaining result of biopsy for ATTR

Exclusion Criteria:

• Evidence of primary (AL) and secondary (AA) amyloidosis AND/OR
• At least one claim/procedure code for stem cell transplant or at least two claims/procedure codes for chemotherapy and autoimmune disease drugs which may represent AL (primary) or AA (secondary) amyloidosis treatments

Study Plan

How is the study designed?

Number of groups / cohorts

6

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
ATTR cardiomyopathy; Patients with Transthyretin Amyloidosis Cardiomyopathy	Other: no intervention; not applicable, this is an observational retrospective data analysis study; no interventions in the study
ATTR polyneuropathy; Patients with Transthyretin Amyloidosis Neuropathy	Other: no intervention; not applicable, this is an observational retrospective data analysis study; no interventions in the study
ATTR unknown; Patients with ATTR unknown genotype	Other: no intervention; not applicable, this is an observational retrospective data analysis study; no interventions in the study
ATTR with mixed phenotype; Patients with ATTR mixed phenotype	Other: no intervention; not applicable, this is an observational retrospective data analysis study; no interventions in the study
ATTR wild type; Patients with Transthyretin Amyloidosis wild type	Other: no intervention; not applicable, this is an observational retrospective data analysis study; no interventions in the study
ATTR hereditary; Patients with Transthyretin Hereditary	Other: no intervention; not applicable, this is an observational retrospective data analysis study; no interventions in the study

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Health Care Resource Utilization (HCRU) - Outpatient visits	Annualized events rate for: Overall outpatient visits	From diagnosis of ATTR amyloidosis (index date), assessed throughout the study until end of follow-up, up to a maximum of 12 years
Health Care Resource Utilization (HCRU) - Outpatient visits by specialty	Annualized events rate for: Overall outpatient visits by specialty	From diagnosis of ATTR amyloidosis (index date), assessed throughout the study until end of follow-up, up to a maximum of 12 years
Health Care Resource Utilization (HCRU) - Emergency department visits	Annualized events rate for: Emergency department visits	From diagnosis of ATTR amyloidosis (index date), assessed throughout the study until end of follow-up, up to a maximum of 12 years
Health Care Resource Utilization (HCRU) - Hospitalizations, length of stay	Annualized events rate for: Hospitalizations (bed days)	From diagnosis of ATTR amyloidosis (index date), assessed throughout the study until end of follow-up, up to a maximum of 12 years
Health Care Resource Utilization (HCRU) - Hospitalizations	Annualized events rate for: Hospitalizations Overlaps (e.g., hospitalization after emergency department visit) are allowed and counted as separate visits	From diagnosis of ATTR amyloidosis (index date), assessed throughout the study until end of follow-up, up to a maximum of 12 years
Health Care Resource Utilization (HCRU) - Health care cost	This variable will describe all-cause direct medical and pharmacy costs only, utilizing the amount charged, where available in the data. The direct medical costs will include costs incurred from inpatient stays, outpatient visits, emergency room visits, procedures, and laboratory tests. The inclusion of pharmacy costs is subject to data availability and will include all pharmacy costs per patient separated on pharmacy dispensed and in-hospital dispensed when possible. When feasible, costs will be divided on all-cause, CV, and other specialties	From diagnosis of ATTR amyloidosis (index date), assessed throughout the study until end of follow-up, up to a maximum of 12 years
Cardiac transplant	Cardiac transplant (Time to event)	From diagnosis of ATTR amyloidosis (index date) until date of first cardiac transplant, assessed throughout the study until end of follow-up, up to a maximum of 12 years
All cause mortality	Mortality (time-to-event)	From diagnosis of ATTR amyloidosis (index date) until date of death due to any cause, assessed throughout the study until end of follow-up, up to a maximum of 12 years
Liver transplant	Liver transplant (time-to-event)	From diagnosis of ATTR amyloidosis (index date) until date of first liver transplant, assessed throughout the study until end of follow-up, up to a maximum of 12 years
Heart Failure Hospitalization	Heart failure hospitalization (time-to-event)	From diagnosis of ATTR amyloidosis (index date) until date of first hospitalization for heart failure, assessed throughout the study until end of follow-up, up to a maximum of 12 years
New ATTR amyloidosis clinical manifestation	New amyloidosis manifestation (time-to-event); Time to the first development of a new clinical manifestation that the patient did not have pre-index)	From diagnosis of ATTR amyloidosis (index date) until date of first diagnosis of new ATTR amyloidosis clinical manifestation, assessed throughout the study until end of follow-up, up to a maximum of 12 years
Hospitalization (any cause)	Time to hospitalization (all-cause)	From diagnosis of ATTR amyloidosis (index date) until date of first hospitalization for any reason, assessed throughout the study until end of follow-up, up to a maximum of 12 years
Neuropathy Impairment Score (NIS)	The NIS Score has a range of 0 to 244 and a higher NIS score indicates poorer function	From diagnosis of ATTR amyloidosis (index date), assessed throughout the study until end of follow-up, up to a maximum of 12 years
Neuropathy Impairment Score Lower Limbs (NIS-LL)	The NIS-LL score has a range of 0-88 and a greater NIS-LL score indicates poorer function	From diagnosis of ATTR amyloidosis (index date), assessed throughout the study until end of follow-up, up to a maximum of 12 years
Neuropathy Impairment Score +7 (NIS+7)	The NIS+7 Score has a range of -26.04 to 270.04 and a higher NIS+7 score indicates poorer function	From diagnosis of ATTR amyloidosis (index date), assessed throughout the study until end of follow-up, up to a maximum of 12 years
Neuropathy Impairment Score modified +7 (mNIS+7)	The mNIS+7 Score has a range of -22.32 to 102.32 and a higher mNIS+7 score indicates poorer function	From diagnosis of ATTR amyloidosis (index date), assessed throughout the study until end of follow-up, up to a maximum of 12 years
Neuropathy symptoms and change (NCS) score	NSC score is a questionnaire composed of 38 questions that assess the presence and severity of these neuropathy symptoms. The NSC score ranges from -114 to 114 for males and -108 to 108 for females. Greater scores indicate worse symptom severity; a negative value indicates an improvement in symptom severity from baseline	From diagnosis of ATTR amyloidosis (index date), assessed throughout the study until end of follow-up, up to a maximum of 12 years
PND (Polyneuropathy Disability)	The PND is a 6-stage scoring system: Stage 0: no impairment; Stage 1: sensory disturbances but preserved walking capabilities; Stage 2: impaired walking capacity, but ability to walk without a stick or crutches; Stage 3A/B: walking with help of 1 or 2 sticks or crutches; Stage 4: confined to wheel chair or bedridden. A greater stage indicates greater impairment	From diagnosis of ATTR amyloidosis (index date), assessed throughout the study until end of follow-up, up to a maximum of 12 years
Other relevant clinical measurement of ATTR amyloidosis functional status	Any other relevant clinical measurement of ATTR amyloidosis functional status	From diagnosis of ATTR amyloidosis (index date), assessed throughout the study until end of follow-up, up to a maximum of 12 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Health Care Resource Utilization (HCRU) - Outpatient visits	Annualized events rate for: Overall outpatient visits	From up to 12 years prior to ATTR amyloidosis diagnosis, assessed throughout the study, up to a maximum of 12 years.
Health Care Resource Utilization (HCRU) - Outpatient visits by specialty	Annualized events rate for: Overall outpatient visits by specialty	From up to 12 years prior to ATTR amyloidosis diagnosis, assessed throughout the study, up to a maximum of 12 years.
Health Care Resource Utilization (HCRU) - Emergency department visits	Annualized events rate for: Emergency department visits	From up to 12 years prior to ATTR amyloidosis diagnosis, assessed throughout the study, up to a maximum of 12 years.
Health Care Resource Utilization (HCRU) - Hospitalizations, length of stay	Annualized events rate for: Hospitalizations (bed days)	From up to 12 years prior to ATTR amyloidosis diagnosis, assessed throughout the study, up to a maximum of 12 years.
Health Care Resource Utilization (HCRU) - Hospitalizations	Annualized events rate for: Hospitalizations Overlaps (e.g., hospitalization after emergency department visit) are allowed and counted as separate visits	From up to 12 years prior to ATTR amyloidosis diagnosis, assessed throughout the study, up to a maximum of 12 years.
Health Care Resource Utilization (HCRU) - Health care cost	This variable will describe all-cause direct medical and pharmacy costs only, utilizing the amount charged, where available in the data. The direct medical costs will include costs incurred from inpatient stays, outpatient visits, emergency room visits, procedures, and laboratory tests. The inclusion of pharmacy costs is subject to data availability and will include all pharmacy costs per patient separated on pharmacy dispensed and in-hospital dispensed when possible. When feasible, costs will be divided on all-cause, CV, and other specialties	From up to 12 years prior to ATTR amyloidosis diagnosis, assessed throughout the study, up to a maximum of 12 years.

Collaborators and Investigators

• Sponsor: AstraZeneca

Publications and helpful links

General Publications

• Gillmore JD, Hahn K, Smith JG, Conceicao I, Tian Z, Grogan M, Pao C, Wittbrodt E, Jarbrink K, Papas MA, Davis MK. Rationale and Design of ANTHOLOGY: An ATTR Amyloidosis Real-World Evidence Program Aiming to Address Gaps in Amyloidosis Care. Cardiol Ther. 2025 Sep;14(3):477-490. doi: 10.1007/s40119-025-00402-y. Epub 2025 Mar 19.

Study record dates

Study Major Dates

• Study Start (Actual): August 21, 2023
• Primary Completion (Estimated): September 30, 2026
• Study Completion (Estimated): September 30, 2026

Study Registration Dates

• First Submitted: February 12, 2024
• First Submitted That Met QC Criteria: April 3, 2024
• First Posted (Actual): April 10, 2024

Study Record Updates

• Last Update Posted (Actual): May 19, 2026
• Last Update Submitted That Met QC Criteria: May 18, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: ATTR-CM, ATTRv-PN
• Additional Relevant MeSH Terms: Metabolic Diseases; Proteostasis Deficiencies; Amyloidosis
• Other Study ID Numbers: D8450R00004

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 rerefer 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.

Signed Data Usage Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information.