Global Prevalence of ATTR-CM in Participants With HFpEF

GLOBAL PREVALENCE OF TRANSTHYRETIN AMYLOID CARDIOMYOPATHY (ATTR-CM) IN PARTICIPANTS WITH HEART FAILURE WITH PRESERVED EJECTION FRACTION (HFpEF)

This study is a global, multi-center study designed to estimate the global prevalence of transthyretin amyloid cardiomyopathy (ATTR-CM) within a clinically at risk population [participants with heart failure with preserved ejection fraction (HFpEF)].

Study Overview

• Status: Terminated
• Conditions: Heart Failure With Preserved Ejection Fraction; Transthyretin Amyloid Cardiomyopathy
• Intervention / Treatment: Diagnostic test: Scintigraphy

• Study Type: Interventional
• Enrollment (Actual): 347
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Ottawa, Ontario, Canada, K1Y 4W7
      • University of Ottawa Heart Institute
  • Quebec
    • Saint-Jean-sur-Richelieu, Quebec, Canada, J3A 1C3
      • CardioVasc HR Inc
    • Trois-Rivieres, Quebec, Canada, G9A 4P3
      • Diex Recherche Trois-rivieres
• France
  • Bron Cedex, France, 69677
    • Hopital Louis Pradel
  • LYON cedex 07, France, 69365
    • Centre Hospitalier Saint-Joseph Saint-Luc
  • Nimes, France, 30029
    • CHU Nimes - Hospital Caremeau
  • Toulouse cedex 9, France, 50032 - 31059
    • CHU de Toulouse - Hôpital de Rangueil
  • Villeurbanne, France, 69100
    • Médecine Nucléaire de la Doua
• Italy
  • Genova, Italy, 16132
    • U.O. Clinica delle Malattie dell'Apparato Cardiovascolare - Ospedale Policlinico San Martino IRCCS
  • Pavia, Italy, 27100
    • Fondazione IRCCS Policlinico San Matteo - Centro per lo Studio e la Cura delle Amiloidosi Sistemiche
  • Pisa, Italy, 56124
    • Fondazione Toscana Gabriele Monasterio-UOC Cardiologia e Medicina Cardiovascolare
  • BO
    • Bologna, BO, Italy, 40138
      • IRCCS Azienda Ospedaliero-Universitaria di Bologna, Policlinico di Sant'Orsola
  • Genoa
    • Genova, Genoa, Italy, 16132
      • U.O. Clinica delle Malattie dell'Apparato Cardiovascolare - Ospedale Policlinico San Martino IRCCS
• Japan
  • Okayama, Japan, 700-8558
    • Okayama University Hospital
  • Aichi
    • Kasugai, Aichi, Japan, 487-0016
      • Nagoya Tokushukai General Hospital
  • Fukuoka
    • Kasuga, Fukuoka, Japan, 816-0864
      • Fukuoka Tokushukai Hospital
  • Tokyo
    • Shinjuku-ku, Tokyo, Japan, 160-8582
      • Keio University Hospital
• Poland
  • Dolnoslaskie
    • Wroclaw, Dolnoslaskie, Poland, 50-556
      • Uniwersytecki Szpital Kliniczny im. Jana Mikulicza-Radeckiego we Wrocławiu
  • Dolnośląskie
    • Wrocław, Dolnośląskie, Poland, 50-556
      • Uniwersytecki Szpital Kliniczny im. Jana Mikulicza-Radeckiego we Wrocławiu
  • Malopolskie
    • Krakow, Malopolskie, Poland, 31-202
      • Krakowski Szpital Specjalistyczny im. Jana Pawła II
  • Podlaskie
    • Białystok, Podlaskie, Poland, 15-276
      • Uniwersytecki Szpital Kliniczny w Białymstoku
  • Łódzkie
    • Łódź, Łódzkie, Poland, 90-549
      • SPZOZ Uniwersytecki Szpital Kliniczny Im. Wojskowej Akademii Medycznej UM W Łodzi Centralny Szpital
• Spain
  • Barcelona, Spain, 08036
    • Hospital Clinic De Barcelona
  • Barcelona, Spain, 08907
    • Hospital Universitari de Bellvitge
  • Barcelona, Spain, 08035
    • Hospital Universitari Vall d´Hebrón
  • Madrid, Spain, 28034
    • Hospital Universitario Ramon y Cajal
  • Salamanca, Spain, 37007
    • Hospital Universitario de Salamanca - Complejo Asistencial Universitario de Salamanca
  • Valencia, Spain, 46026
    • Hospital Universitari i Politecnic La Fe
  • Madrid
    • Majadahonda, Madrid, Spain, 28222
      • Hospital Universitario Puerta de Hierro Majadahonda
• United Kingdom
  • London, United Kingdom, SW17 0QT
    • St George's Hospital, St George's University Hospitals NHS Foundation Trust
• United States
  • Alabama
    • Fairhope, Alabama, United States, 36532
      • Eastern shore Research Institute LLC
    • Huntsville, Alabama, United States, 35801
      • Heart Center Research, LLC
  • Florida
    • Miami, Florida, United States, 33135
      • Advance Medical Research Center
    • Miami, Florida, United States, 33165
      • Biogenix Molecular
    • Miami, Florida, United States, 33155
      • Bioclinical Research Alliance Inc.
    • Miami, Florida, United States, 33165
      • CIRA (Nuclear Imaging Facility)
    • Miami, Florida, United States, 33165
      • Nucleotron/ Doral Imaging Institute, CIRA DBA
    • Miami, Florida, United States, 33175
      • Innova Pharma Research
    • Ocala, Florida, United States, 34471
      • Ocala Cardiovascular Research
  • Illinois
    • Hazel Crest, Illinois, United States, 60429
      • Chicago Medical Research, LLC
    • Oak Lawn, Illinois, United States, 60453
      • Advocate Christ Medical Center
  • Kansas
    • Topeka, Kansas, United States, 66604
      • Stormont Vail Health
    • Topeka, Kansas, United States, 66606
      • Cotton O'Neil Heart Center
  • Louisiana
    • New Orleans, Louisiana, United States, 70121
      • Ochsner Medical Center
  • Michigan
    • Grand Rapids, Michigan, United States, 49503
      • Corewell Health
    • Grand Rapids, Michigan, United States, 49525
      • Spectrum Health Medical Group Cardiovascular Medicine
  • Mississippi
    • Tupelo, Mississippi, United States, 38801
      • Cardiology Associates Research, LLC
    • Tupelo, Mississippi, United States, 38801
      • Cardiology Associates of North Mississippi, LLC
  • New York
    • New York, New York, United States, 10016
      • NYU Langone Health
  • North Carolina
    • Raleigh, North Carolina, United States, 27610
      • Wakemed Health and Hospital
  • Tennessee
    • Jackson, Tennessee, United States, 38301
      • The Jackson Clinic
  • Washington
    • Spokane, Washington, United States, 99204
      • Providence Sacred Heart Medical Center and Children's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 60 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Medical history of heart failure (HF) with:

   1. At least 1 episode with clinical evidence of HF (without hospitalization) by signs or symptoms of volume overload or elevated intracardiac pressures that required/requires treatment with a diuretic for improvement; OR
   2. 1 prior hospitalization for HF.
2. Left ventricular ejection fraction (LVEF) >40%.
3. End-diastolic interventricular septal wall thickness (IVST) ≥12 mm.
4. Willing and able to undergo scintigraphy.

Exclusion Criteria:

1. Diagnosis of heart failure with reduced ejection fraction (HFrEF) (EF ≤40%).
2. Prior clinical history of myocardial infarction, CABG or multi-vessel obstructive coronary disease (>50% stenosis of ≥2 epicardial coronary arteries).
3. Presence or history of any severe valvular heart disease (obstructive or regurgitant).
4. A confirmed diagnosis of a non-amyloid infiltrative cardiomyopathy (ie, cardiac sarcoidosis, hemochromatosis), muscular dystrophies, cardiomyopathy with reversible causes, hypertrophic obstructive cardiomyopathy with known genetic etiology, or known pericardial constriction.

5. Any type of diagnosed amyloidosis (eg, amyloid A amyloidosis, primary [light chain] amyloidosis) or prior diagnosis of ATTR-CM.

   -

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Screening
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: ATTR-CM positive; Participants diagnosed with ATTR-CM by scintigraphy	Diagnostic test: Scintigraphy; scintigraphy
Other: ATTR-CM negative; Participants who are scintigraphy negative for ATTR-CM	Diagnostic test: Scintigraphy; scintigraphy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Global Prevalence of ATTR-CM in HFpEF Participants Clinically At-Risk of Disease Among Total Evaluable Participants	Global prevalence of ATTR-CM in HFpEF participants was obtained by dividing the number of participants who were diagnosed with ATTR-CM in the study by the total number of HFpEF participants evaluated. Diagnosis of ATTR-CM was defined as: cardiac scintigraphy Grade 1, with confirmation of ATTR by cardiac biopsy; or cardiac scintigraphy Grade 2 or above. Exact 95% confidence intervals for the prevalence estimates were calculated using the method of Clopper and Pearson.	Day 1

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Global Prevalence of ATTR-CM in Participants With HFpEF Clinically At-Risk of Disease by Subgroups (Regions, Age, Gender) Among Total Evaluable Participants	The prevalence of ATTR-CM in HFpEF participants was evaluated for subgroups including regions (North America, Europe, and Asia), age categories (60-64 years, 65-69 years, 70-74 years, 75-79 years, 80-85 years, 85-89 years, >=90 years), and gender (male, female). The estimate of prevalence was defined as the number of participants meeting the diagnosis criteria of ATTR-CM divided by the number of evaluable participants in the study in the given subgroup category. Diagnosis of ATTR-CM was defined as: cardiac scintigraphy Grade 1, with confirmation of ATTR by cardiac biopsy; or cardiac scintigraphy Grade 2 or above. Exact 95% confidence intervals for the prevalence estimates were calculated using the method of Clopper and Pearson.	Day 1
Number of Participants According to TTR Genotypes Among Participants Diagnosed With ATTR-CM	Number of participants diagnosed with ATTR-CM were evaluated for TTR genotypes (wild-type or hereditary form).	Day 1
Number of HFpEF Participants With and Without ATTR-CM Based on New York Heart Association (NYHA) Classification	Participants were evaluated using the NYHA classification at Day 1. Class I: participants with cardiac disease but without resulting limitations of physical activity. Class II: participants with cardiac disease resulting in slight limitation of physical activity. Class III: participants with cardiac disease resulting in marked limitation of physical activity. Class IV: participants with cardiac disease resulting in inability to carry on any physical activity without discomfort.	Day 1
N-terminal Pro-brain Natriuretic Peptide (NT-proBNP) in Participants With and Without ATTR-CM	Participants were evaluated using NT-proBNP cardiac biomarker that was assessed at Day 1.	Day 1

Collaborators and Investigators

• Sponsor: Pfizer
• Investigators: Study Director: Pfizer CT.gov Call Center, Pfizer

Publications and helpful links

Helpful Links

• To obtain contact information for a study center near you, click here.

Study record dates

Study Major Dates

• Study Start (Actual): December 30, 2020
• Primary Completion (Actual): June 2, 2023
• Study Completion (Actual): June 2, 2023

Study Registration Dates

• First Submitted: May 27, 2020
• First Submitted That Met QC Criteria: June 5, 2020
• First Posted (Actual): June 11, 2020

Study Record Updates

• Last Update Posted (Actual): July 19, 2024
• Last Update Submitted That Met QC Criteria: February 1, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: prevalence; scintigraphy; HFpEF; ATTR-CM; transthyretin amyloid
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Metabolic Diseases; Proteostasis Deficiencies; Heart Failure; Amyloidosis; Cardiomyopathies
• Other Study ID Numbers: B3461087; HFpEF ATTR-CM prevalence study (Other Identifier: Alias Study Number); 2020-002378-29 (EudraCT Number); ATTR-POP (Other Identifier: Alias Study Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.

Drug and device information, study documents

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