Retinal Fundus Imaging and OCT Imaging for Ocular Detection of ATTR-CM

A Multicenter Pilot Study to Investigate Ocular Involvement and the Potential of Ocular Imaging for Non-invasive Screening for Transthyretin Amyloid Cardiomyopathy (ATTR-CM)

This multicenter pilot study will enroll adult participants with a confirmed clinical diagnosis of transthyretin amyloid cardiomyopathy (ATTR-CM) and heart failure (HF) controls with documentation within the past 2 years that either excludes ATTR-CM or indicates a low probability of ATTR-CM. Ocular imaging and other study data will be collected to assess the feasibility of developing and preliminarily evaluating a machine learning model to discriminate ATTR-CM cases from HF controls without ATTR-CM.

Study Overview

• Status: Not yet recruiting
• Conditions: Transthyretin Amyloid Cardiomyopathy

Detailed Description

A participant who does not complete the study within 90 days from enrollment will be discontinued from the study. A participant may be discontinued from the study at any time at the discretion of the investigator for behavioral or compliance reasons. A participant may withdraw from the study at any time at the participant's own request for any reason (or without providing any reason) without any implication on participant's rights.

• Study Type: Observational
• Enrollment (Estimated): 500

Contacts and Locations

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

Study Locations

• Germany
  • Essen, Germany, 45147
    • Research Site
  • Würzburg, Germany, 97078
    • Research Site
• Portugal
  • Guimarães, Portugal, 4835-044
    • Research Site
• Spain
  • L'Hospitalet de Llobregat, Spain, 08907
    • Research Site
  • Palma de Mallorca, Spain, 07198
    • Research Site
• United States
  • California
    • Palo Alto, California, United States, 94305
      • Research Site
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Research Site
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Research Site
  • Oregon
    • Portland, Oregon, United States, 97239-3098
      • Research Site
  • Tennessee
    • Germantown, Tennessee, United States, 38138
      • Research Site

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Non-Probability Sample

Study Population

The study population will comprise adult participants with a confirmed clinical diagnosis of transthyretin amyloid cardiomyopathy (ATTR-CM) and heart failure (HF) controls who have documentation within the past 2 years that either excludes ATTR-CM or indicates a low probability of ATTR-CM.

Description

Inclusion Criteria:

• 1. Participant must be 18 years and older at the time of signing the informed consent form.
• 2. Participants with either of the following:
• - Positive ATTR-CM cases: Participants with a clinical diagnosis of transthyretin amyloid cardiomyopathy (ATTR-CM) with amyloid deposits in cardiac or non-cardiac tissue confirmed by Congo Red (or equivalent) staining, or DPD-Tc, PYP-Tc, or HMDP-Tc scintigraphy with Grade 2 or 3 cardiac uptake in the absence of abnormal light chains ratio.
• - Control population: Participants with a clinical diagnosis of guideline-directed medical therapy-directed heart failure (HF) and either:
• a) Subgroup A: Definitively excluded ATTR-CM amyloidosis: negative cardiac or non-cardiac tissue biopsy for amyloid, or negative technetium scintigraphy within the past 2 years.
• b) Subgroup B: Low probability of ATTR-CM amyloidosis, not definitively excluded: absence of amyloid-suggestive features on echocardiography (ECHO), electrocardiography (ECG), or cardiac magnetic resonance imaging (MRI) within the past 2 years, with documented clinical assessment indicating HF etiology unlikely attributable to amyloidosis; no amyloid-specific testing (technetium scintigraphy or biopsy) performed.
• 3. Participant or legally authorized representative (LAR) must sign the informed consent form.

Exclusion Criteria:

• 1. Any known eye condition that may preclude clear imaging of the retina.
• 2. Any known history of amyloid light-chain (AL) amyloidosis.
• 3. Any ocular surgery that, in the opinion of the investigator, makes participation in the study undesirable.
• 4. Any medical condition that, in the opinion of the investigator, makes participation in the study undesirable, for example, if the participant is critically unwell or requires ongoing emergency treatment.
• 5. Involvement in the planning and/or conduct of the study.
• 6. In the opinion of the investigator, the participant is unlikely to comply with study procedures, restrictions, and requirements.
• 7. Previous enrollment in the present study.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
ATTR-CM; Participants with a confirmed clinical diagnosis of transthyretin amyloid cardiomyopathy (ATTR-CM).
HF Control; Participants with guideline-directed medical therapy-directed heart failure and documentation within the past 2 years that either excludes transthyretin amyloid cardiomyopathy (ATTR-CM) or indicates a low probability of ATTR-CM.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Comparison of per-participant confidence scores distributions between ATTR-CM cases and HF controls without ATTR-CM	Per-participant confidence score distributions generated by the machine learning (ML) model will be compared between participants with clinically confirmed transthyretin amyloid cardiomyopathy (ATTR-CM) and heart failure controls without ATTR-CM.	At a single assessment time point within 90 days following informed consent form signing
Qualitative assessment of features learned indicative of ATTR pathology	Features learned by the machine learning (ML) model that are indicative of transthyretin amyloid pathology will be qualitatively assessed.	At a single assessment time point within 90 days following informed consent form signing

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Sensitivity, specificity, and Area Under the Receiver Operating Characteristic Curve (AUROC) of the ML model to correctly identify ATTR-CM cases based on ocular imaging data	Sensitivity, specificity, and area under the receiver operating characteristic curve will be used to describe the performance of the machine learning model for distinguishing participants with clinically confirmed transthyretin amyloid cardiomyopathy (ATTR-CM) from heart failure controls without ATTR-CM based on ocular imaging data.	At a single assessment time point within 90 days following informed consent form signing
Descriptive comparison of score distributions across study population strata and demographics	Score distributions generated by the machine learning model will be descriptively compared across study population strata and demographic groups.	At a single assessment time point within 90 days following informed consent form signing

Collaborators and Investigators

• Sponsor: AstraZeneca

Study record dates

Study Major Dates

• Study Start (Estimated): July 2, 2026
• Primary Completion (Estimated): June 3, 2027
• Study Completion (Estimated): June 3, 2027

Study Registration Dates

• First Submitted: July 2, 2026
• First Submitted That Met QC Criteria: July 2, 2026
• First Posted (Actual): July 8, 2026

Study Record Updates

• Last Update Posted (Actual): July 8, 2026
• Last Update Submitted That Met QC Criteria: July 2, 2026
• Last Verified: July 1, 2026

More Information

Terms related to this study

• Keywords: Heart Failure; Optical coherence tomography; Machine Learning; ATTR-CM; Transthyretin Amyloid Cardiomyopathy; Ocular Imaging; Retinal fundus imaging
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Heart Diseases; Heart Failure
• Other Study ID Numbers: D8455R00001

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.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No