Transthyretin Amyloidosis Outcome Survey (THAOS) (THAOS)

Transthyretin Amyloidosis Outcomes Survey (THAOS): A Global, Multi-Center, Longitudinal, Observational Survey of Patients With Documented Transthyretin Gene Mutations or Wild-Type Transthyretin Amyloidosis.

THAOS is a global, multi-center, longitudinal observational survey open to all patients with transthyretin amyloidosis (ATTR), including ATTR-PN (polyneuropathy), ATTR-CM (cardiomyopathy) and wild-type ATTR-CM. It is open-ended with a minimum duration of 10 years. Patients will be followed as long as they are able to participate. The principal aims of this outcome survey are to better understand and characterize the natural history of the disease by studying a large and heterogenous patient population. Survey data may be used to develop new treatment guidelines and recommendations, and to inform and educate clinicians about the management of this disease.

Study Overview

• Status: Completed
• Conditions: Transthyretin Amyloidosis; Transthyretin Gene Mutations
• Intervention / Treatment: Other: None. Observational Study.

Detailed Description

n/a NA

• Study Type: Observational
• Enrollment (Actual): 6718

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina, 1199ABB
    • Hospital Italiano de Buenos Aires (HIBA)
  • Ciudad Autonoma De Buenos Aires, Argentina
    • Instituto De Investigaciones Medicas Dr Alfredo Lanari
  • Ciudad Autonoma de Buenos aires, Argentina, C1428AQK
    • FLENI
• Belgium
  • Leuven, Belgium, 3000
    • Afdeling Klinische Cardiologie, O&N I
• Brazil
  • Rio de Janeiro, Brazil, 21941-913
    • Hospital Universitário Clementino Fraga Filho -HUCFF Universidade Federal do Rio de Janeiro
  • Sao Paulo, Brazil, 04012-909
    • Instituto Dante Pazzanese de Cardiologia
• Bulgaria
  • Sofia, Bulgaria, 1431
    • Alexandrovska University Hospital Clinic of Neurology
• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2N 4Z6
      • University of Alberta Foothills Medical Centre
  • Ontario
    • Toronto, Ontario, Canada, M5G 2N2
      • Toronto General Hospital
    • Toronto, Ontario, Canada, M5G 2C4
      • Toronto General Hospital-University Health Network
• Cyprus
  • Nicosia, Cyprus, 23462
    • Cyprus Institute of Neurology and Genetics
• Denmark
  • Aarhus, Denmark, 8200
    • Aarhus University Hospital, Skejby
• France
  • Cedex, France, 94275
    • CHU de Bicetre
  • Colmar, France, 68024
    • Hopital Louis Pasteur
  • Créteil, France, 94000
    • Chu Henri Mondor
  • Fort De France, France, 97200
    • CHU de Fort de France
  • Lille, France, 59037
    • CHRU de Lille, Hôpital Claude Huriez
  • Lille, France, 59037
    • Hopital Salengro - CHRU de Lille
  • Toulouse cedex 09, France, 31059
    • CHU de Toulouse - Hôpital Rangueil
• Germany
  • Aachen, Germany, 52074
    • University Hospital of RWTH Aachen
  • Berlin, Germany, 13353
    • Charite CAmpus Rudolf-Virchow-Klinikum
  • Heidelberg, Germany, D-69120
    • Medical University of Heidelberg
  • Mainz, Germany, 55131
    • Johann-Gutenberg-Universität
  • Mainz, Germany, 55131
    • University Medical Center, Johannes Gutenberg-University Mainz
  • Mainz, Germany, 55131
    • Universitätsmedizin der Johannes Gutenberg Universität Mainz KöR
  • Muenster, Germany, 48149
    • Universitatsklinikum Muenster - Transplant Hepatology
• Israel
  • Holon, Israel, 58100
    • Wolfson Medical Center
  • Ramat Gan, Israel, 52621
    • Sheba Medical Center
• Italy
  • Bologna, Italy, 40138
    • Comitato Etico Indipendente dell Azienda
  • Firenze, Italy, 50134
    • Azienda Ospedaliero-Universitaria di Careggi
  • Messina, Italy, 98125
    • AOU Policlinico G. Martino - Messina - Comitato Etico Scientifico
  • Messina, Italy, 98125
    • AOU Policlinico G. Martino - Messina - Dr. Vita
  • Pavia, Italy, 27100
    • Centro per lo Studio e la Cura delle Amiloidosi Sistemiche - Pavia - Prof. Merlini
  • Pavia, Italy, 27100
    • Comitato di Bioetica della Fondazione IRCCS Policlinico S. Matteo
  • Pisa, Italy, 56126
    • Fondazione Toscana Gabriele Monasterio Per La Ricerca Medica E Di Sanita Pubblica (Ftgm)
  • Roma, Italy, 00168
    • Fondazione Policlinico Gemelli - Universita Cattolica del Sacro Cuore
• Japan
  • Chiba, Japan, 260-8677
    • Chiba University Hospital
  • Kumamoto, Japan, 860-8556
    • Kumamoto University
  • JP
    • Matsumoto, JP, Japan, 390-8621
      • Shinshu University School of Medicine
• Korea, Republic of
  • Seoul, Korea, Republic of, 143-729
    • Konkuk University Medical Center
  • Seoul, Korea, Republic of, 135-710
    • Samsung Medical Center, Sungkyunkwan University School of Medicine
• Malaysia
  • Wilayah Persekutuan
    • Kuala Lumpur, Wilayah Persekutuan, Malaysia, 59100
      • University Malaya Medical Centre (UMMC)
• Mexico
  • Distrito Federal, Mexico, 14000
    • Instituto Nacional de Ciencia Medicas y Nutricion Salvador Zubiran
• Netherlands
  • Groningen, Netherlands, 9713 GZ
    • University Medical Center Groningen
• Portugal
  • Guimaraes, Portugal, 4835-004
    • Centro Hospitalar Do Alto Ave, Epe
  • Lisboa, Portugal, 1649-035
    • Hospital Santa Maria
  • Lisboa, Portugal, 1649-035
    • Centro Hospitalar Lisboa Norte (CHLN) EPE - Hospital de Santa Maria
  • Porto, Portugal, 4099-001
    • Unidade Clinica de Paramiloidose-Centro Hospitalar Porto,EPE-Hospital Geral Santo Antonio
• Romania
  • Bucuresti, Romania, 022328
    • Institutul De Cardiologie Prof. Dr. C. C. Iliescu Spitalului Fundeni
• Saudi Arabia
  • Riyadh, Saudi Arabia, 11564
    • King Faisal Specialist Hospital and Research Center
• Spain
  • Barcelona, Spain, 08907
    • Hospital Universitari de Bellvitge
  • Barcelona, Spain, 08036
    • Institut Clinic de Nefrologia i Urologia - ICNU, Hospital Clinic i Provincial de Barcelona
  • Granada, Spain, 18013
    • Hospital de Rehabilitacion y Traumatologia Virgen de las Nieves
  • Huelva, Spain, 21005
    • Hospital Juan Ramón Jimenez
  • Madrid, Spain, 28040
    • Hospital Clinico San Carlos
  • Madrid, Spain, 28007
    • Hospital Gregorio Maranon
  • Palma de Mallorca, Spain, 07198
    • Hospital Son Llatzer
  • Donostia
    • Gipuzkoa - SanSebastian, Donostia, Spain, 20014
      • Hospital Universitario Donostia
  • Madrid
    • Majadahonda, Madrid, Spain, 28220
      • Hospital Universitario Puerta de Hierro
• Sweden
  • Piteå, Sweden, 941 50
    • Piteå Älvdals Hospital
  • Stockholm, Sweden, 141 86
    • Karolinska University Hospital, Huddinge
  • Umeå, Sweden
    • Umea University Hospital
• Taiwan
  • Taipei, Taiwan, 100
    • National Taiwan University Hospital
  • Taipei, Taiwan, 10018
    • National Taiwan University Hospital
• Turkey
  • Istanbul, Turkey, 34093
    • Istanbul University,Istanbul Faculty of Medicine,Department of Neurology
• United Arab Emirates
  • Abu Dhabi, United Arab Emirates
    • Cleveland Clinic Abu Dhabi LLC
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • University of Alabama at Birmingham
  • Arizona
    • Phoenix, Arizona, United States, 85054
      • Mayo Clinic Arizona
  • California
    • Los Angeles, California, United States, 90073
      • VA Greater Los Angeles Healthcare System
    • Orange, California, United States, 92868
      • University of California, Irvine
    • San Francisco, California, United States, 94117
      • University of California - San Francisco, UCSF Department of Neurology
    • San Francisco, California, United States, 94143
      • Office of Sponsored Research
    • Stanford, California, United States, 94305-5406
      • Stanford University School of Medicine
  • Colorado
    • Aurora, Colorado, United States, 80045
      • UC Denver
  • Connecticut
    • New Haven, Connecticut, United States, 06510
      • Smilow Cancer Hospital at Yale-New Haven
  • Florida
    • Deerfield Beach, Florida, United States, 33442
      • UHealth Deerfield Beach
    • Miami, Florida, United States, 33136
      • University of Miami Hospital & Clinics
    • Plantation, Florida, United States, 33324
      • UHealth Plantation
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern University
    • Chicago, Illinois, United States, 60637
      • University of Chicago Medical Center
    • Chicago, Illinois, United States, 60611
      • Clinical Trials Unit
    • Chicago, Illinois, United States, 60637
      • University of Chicago Medical Center IRB
    • Oak Lawn, Illinois, United States, 60453
      • Advocate Christ Medical Centre
  • Louisiana
    • New Orleans, Louisiana, United States, 70121
      • John Ochsner Heart & Vascular Institute
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • University of Maryland
    • Baltimore, Maryland, United States, 21287
      • Johns Hopkins Hospital
    • Baltimore, Maryland, United States, 21201
      • University of Maryland School of Medicine
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Harvard Vanguard Medical Associates
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University School of Medicine
  • New York
    • Bronx, New York, United States, 10461
      • Cardiology Clinic at Montefiore Hutchinson Campus
    • Bronx, New York, United States, 10461
      • Montefiore Medical Center-Jack D. Weiler Hospital
    • Bronx, New York, United States, 10467
      • Congestive Heart Failure Clinic
    • Bronx, New York, United States, 10467
      • Montefiore Moses Division
    • New York, New York, United States, 10016
      • NYU Medical Center
    • New York, New York, United States, 10034
      • Columbia University Medical Center
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic Foundation
    • Columbus, Ohio, United States, 43210
      • The Ohio University College of Medicine
    • Columbus, Ohio, United States, 43221
      • OSU Wexner Medical Center
  • Oregon
    • Portland, Oregon, United States, 97239
      • Oregon Health and Science University
  • Pennsylvania
    • McMurray, Pennsylvania, United States, 15317
      • Peters Township Health and Wellness Pavillion
    • Philadelphia, Pennsylvania, United States, 19140
      • Temple University School of Medicine
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania - Perelman Center for Advanced Medicine
    • Philadelphia, Pennsylvania, United States, 19104
      • Penn Presbyterian Medical Center-University of Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15212
      • Allegheny General Hospital
    • Pittsburgh, Pennsylvania, United States, 15213
      • University of Pittsburgh Medical Center (UPMC)
    • Pittsburgh, Pennsylvania, United States, 15213
      • Admin
    • Wexford, Pennsylvania, United States, 15090
      • Wexford Health and Wellness Pavillion
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt University School of Medicine
    • Nashville, Tennessee, United States, 37232
      • IRB
  • Utah
    • Salt Lake City, Utah, United States, 84132
      • The University of Utah Health Sciences Center
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Medical College of Wisconsin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

The study population includes patients with confirmed hereditary or wild-type ATTR amyloidosis (inclusive of ATTR-PN and ATTR-CM) and those with TTR gene mutations without a diagnosis of ATTR amyloidosis.

Description

Inclusion Criteria: Patients must meet all of the following inclusion criteria to be eligible for inclusion into THAOS:

1. Evidence of a personally signed and dated informed consent document indicating that the participant (or a legally acceptable representative) has been informed of all pertinent aspects of the study.
2. Males and females greater than or equal to 18 years of age.

3. Confirmed genotyped TTR mutation with or without a diagnosis of hereditary or wild-type ATTR amyloidosis. Confirmation of ATTRwt amyloidosis will be determined by genotyped confirmation that patient does not possess a known mutation in TTR gene (ie, is a carrier of wild-type allele only) via genetic testing and one of the following set of criteria (a, b, or c):

   1. Presence of amyloid in cardiac biopsy tissue confirmed as TTR amyloid by mass spectrometry or immunohistochemistry; or
   2. Evidence of cardiac involvement by echocardiogram as defined by left ventricle wall thickness of >12 mm, and presence of amyloid in non-cardiac tissue confirmed as TTR amyloid by mass spectrometry or immunohistochemistry; or
   3. Evidence of cardiac involvement by echocardiogram as defined by left ventricle wall thickness of >12 mm, and presence of amyloid in cardiac tissue indirectly confirmed by scintigraphy with a "bone seeking tracer" eg, 99mTC-DPD [99mTC-3,3-diphosphono-1,2-propano-dicarboxylic acid], 99mTC- PYP [Pyrophosphate], and 99mTC-HMDP [hydroxymethylene diphosphonate] with Perugini grade greater than or equal to 2.

Exclusion Criteria

Patients meeting any of the following will not be included in the study:

1. Patient has evidence of primary (light chain) or secondary amyloidosis.

Study Plan

How is the study designed?

Design Details

• Observational Models: Other
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Observational	Other: None. Observational Study.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)	An AE was any untoward medical occurrence in a participant who administered a medicinal product without regard to possibility of causal relationship with the study treatment. SAE was defined as one of the following: resulted in death; was life-threatening (immediate risk of death); requires inpatient hospitalization or prolongation of hospitalization; resulted in persistent or significant disability/incapacity (substantial disruption of the ability to conduct normal life functions); constituted a congenital anomaly/birth defect. Treatment-emergent AE was defined as an AE with onset date occurring during the on-treatment period. AEs included all SAEs and non-SAEs.	From the start of data collection at Baseline (Day 1) to the end of data collection (Up to 14.4 years)
Number of Participants With Treatment Emergent Treatment Related AEs and SAEs	A treatment-related AE was any untoward medical occurrence attributed to the administered medicinal product in a participant who received study drug. Treatment emergent AEs included both SAEs and all non-SAEs. A treatment-related SAE was a treatment-related AE and was defined as any untoward medical occurrence at any dose that: resulted in death; was life-threatening (immediate risk of death); requires inpatient hospitalization or prolongation of hospitalization; resulted in persistent or significant disability/incapacity (substantial disruption of the ability to conduct normal life functions); constituted a congenital anomaly/birth defect. Causality was assessed by the investigator.	From the start of data collection at Baseline (Day 1) to the end of data collection (Up to 14.4 years)
Number of All-Cause Deaths	Number of deaths due to any cause was analyzed as time from enrollment or first treatment of tafamidis.	From the start of data collection at Baseline (Day 1) to the end of data collection (Up to 14.4 years)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Modified Polyneuropathy Disability (mPND) Scores at Baseline	Modified Polyneuropathy Disability (mPND) is a score that categorizes participants into six stages (0, I,II, IIIa, IIIb, IV) based on mobility status. 0 = No sensory disturbances in the feet and able to walk without difficulty; I=Sensory disturbances in the feet but able to walk without difficulty; II=Some difficulties with walking but can walk without aid; IIIa=Able to walk with 1 stick or crutch; IIIb=Able to walk with 2 sticks or crutches; IV=Not ambulatory, confined to a wheelchair or bedridden. Higher stage indicates lower mobility status.	At the start of data collection at Baseline (Day 1)
Number of Participants With Coutinho Disease Stages at Baseline	Coutinho disease stages is the most common classification used to capture ATTR (Transthyretin Amyloidosis) disease progression. Participants with stage 0 disease are asymptomatic, Participants with stage 1 (mild) disease are ambulatory, Participants with stage 2 (moderate) disease are ambulatory but require assistance and/or have involvement of the upper limbs, and Participants with stage 3 (severe) disease are bedridden or wheelchair-bound.	At the start of data collection at Baseline (Day 1)
Number of Participants With Karnofsky Performance Index at Baseline	Karnofsky performance score is used to quantify participant's general well-being and activities of daily life and participants are classified based on their functional impairment. Karnofsky performance score is 10 level score which ranges between 10 (moribund) to 100 (normal, no evidence of disease). Higher score means higher ability to perform daily tasks.	At the start of data collection at Baseline (Day 1)
Number of Participants With Heart Failure at Baseline	Heart failure, also known as congestive heart failure is a cardiovascular event.	At the start of data collection at Baseline (Day 1)
Number of Participants With New York Heart Association (NYHA) Classifications at Baseline	New York Health Association (NYHA) functional classification included: Class I (no limitation in physical activity, no dyspnea with normal activity), Class II (slight limitation of physical activity; fatigue, palpitation, or dyspnea with ordinary physical activity), Class III (marked limitation of physical activity; fatigue, palpitation, or dyspnea with less than ordinary physical activity) and Class IV (cannot perform a physical activity without any symptoms, dyspnea at rest).	At the start of data collection at Baseline (Day 1)
Number of Participants Diagnosed With ATTR at Baseline	Participants diagnosed with Transthyretin Amyloidosis (ATTR) at baseline with assessed category of yes, no, and unknown.	At the start of data collection at Baseline (Day 1)
Number of Participants With Prior Misdiagnosis at Baseline	Number of participants with ATTR and participants who had prior misdiagnosis at the baseline were reported.	At the start of data collection at Baseline (Day 1)
Number of Participants With ATTR Genotypes at Baseline	Genetic mutation leads to misfolding of protein transthyretin (TTR) which results in ATTR. In this outcome, number of participants with ATTRv mutation type and wild type TTR were reported.	At the start of data collection at Baseline (Day 1)
Number of Participants With Past or Current Clinical Trial Participation at Baseline	Number of participants had previous or current participant in any clinical trials at the baseline.	At the start of data collection at Baseline (Day 1)
Number of Participants With Past or Current Tafamidis Compassionate Use/Early Access or Other Non-commercial Program at Baseline	Number of participants being allowed for the use of Tafamidis when under strict conditions, Tafamidis was in development and made available to groups of participants who have a disease with no satisfactory authorised therapies and who cannot enter clinical trials.	At the start of data collection at Baseline (Day 1)
Number of Participants With Known Family History of Symptomatic ATTR at Baseline	Number of participants whether with family history of symptomatic ATTR amyloidosis at Baseline were reported.	At the start of data collection at Baseline (Day 1)
Number of Affected Generations at Baseline	The mean of affected generations in participants with a known family history was reported.	At the start of data collection at Baseline (Day 1)
Derived Neuropathy Impairment Score-Lower Limb (NIS-LL) at Baseline	Neuropathy Impairment Score - Lower Limb (NIS-LL) assessed motor, sensory and reflex activity specifically in the lower limbs and combined total scores for the lower limbs were collected and reported. Derived NIS LL score extends from 0 (normal functions) to a maximum possible value of 88 points, the scale is additive for all deficits and is applied bilaterally for each modality tested: 1) muscle strength: 0 (normal)-4 (paralysis), higher score = more weakness; 2) sensory and 3) reflex testings: 0=normal, 1=decreased, or 2=absent. Reflex score: 0 (normal)-10 (present), higher score =present in more anatomic sites; Motor score: 0-160 (full range of motion with maximum resistance across all anatomical sites), higher score=more impairment. Sensory Score has a range of 0 to the normal value of 124 where ratings are coded as 0=absent; 1=decreased; 2=normal.	At the start of data collection at Baseline (Day 1)
Body Mass Index (BMI) at Baseline	BMI was calculated by weight divided by height squared and measured as kilogram per square meter (kg/m^2).	At the start of data collection at Baseline (Day 1)
Modified Body Mass Index (mBMI) at Baseline	mBMI was calculated by multiplying BMI by serum albumin levels [gram/liter (g/L)]. mBMI was measured as kg/m^2*g/L. A progressive decline in mBMI indicated worsening of disease severity.	At the start of data collection at Baseline (Day 1)
Sitting Systolic and Diastolic Blood Pressures (SBP and DBP) at Baseline	BP (Blood Pressure) is the pressure of the blood within the arteries. It is produced primarily by the contraction of the heart muscle. BP measurement is recorded by 2 numbers: systolic BP (SBP, BP when heart is contracting; it is the maximum arterial pressure during contraction of left ventricle) and diastolic BP (DBP, BP when heart is relaxing; it is the minimum arterial pressure during relaxation and dilation of ventricles). Available sitting SBP and DBP at Baseline were reported.	At the start of data collection at Baseline (Day 1)
Left Ventricular (LV) Septum Thickness at Baseline	Cardiac amyloidosis is attributable to intramyocardial amyloid infiltration, which leads to a progressive increase of ventricular wall thickness and stiffness. A left ventricular (LV) wall thickness ≥12 mm plus at least one red flag should raise the suspicion of cardiac amyloidosis.	At the start of data collection at Baseline (Day 1)
Left Ventricular (LV) Ejection Fraction at Baseline	Left ventricular dysfunction, a condition in which the left ventricle of the heart exhibits a decreased functionality, was assessed based on systolic ejection fraction. Systolic ejection fraction was the fraction of the end-diastolic volume (EDV) that was ejected out of left ventricle with each contraction.	At the start of data collection at Baseline (Day 1)
Euro Quality of Life-5 Dimensions-3 Level (EQ-5D-3L): Visual Analog Scale (VAS) Overall Health Score at Baseline	EQ-5D-3L VAS: participant rated questionnaire to assess generic health status in two parts: single utility score and visual analog scale. The VAS component rated the current health state on a scale ranging from 0 (worst imaginable health state) to 100 (best imaginable health state); higher scores indicating a better health state.	At the start of data collection at Baseline (Day 1)
EQ-5D-3L: VAS Derived Index at Baseline	The EQ-5D-3L VAS derived index is calculated by subtracting the values of the descriptive EQ-5D system from the numerical value. This corresponds to the best possible health status, the scale of the Derived Index is 0 [death] to 1 [perfect health]. EQ-5D-3L VAS overall health score and derived score data were sourced from different part of the EQ-5D questionnaire and are conceptually different from each other as EQ VAS is a 0-100 scale and EQ-5D index is a value attached to an EQ-5D profile according to a set of weights that reflect, on average, participant's preferences about how good or bad the state is. More data were collected for EQ-5D index score compared to EQ VAS overall health score at the baseline.	At the start of data collection at Baseline (Day 1)
Norfolk Total Quality of Life (QoL) Score at Baseline	Norfolk QOL: 35-item participant-rated questionnaire used to assess impact of neuropathy on the quality of life of participants diagnosed with ATTR. Scoring was based on 35 questions that yield a TQOL as well as 5 subscale scores: activities of daily living, large fiber neuropathy/physical functioning, small fiber neuropathy, autonomic neuropathy, and symptoms. TQOL= sum of all the items, total possible score range= -2 to 138, where higher score=worse quality of life.	At the start of data collection at Baseline (Day 1)
Number of Participants With Abnormal Electrocardiogram (ECG) at Baseline	Following parameters were analyzed: heart rate, PR interval, QT interval, QRS interval and QT interval corrected using Fridericia's formula (QTcF). Abnormal findings in ECG were based on investigator's discretion.	At the start of data collection at Baseline (Day 1)
Number of Participants With Atrial Fibrillation/Flutter, Pacemaker Implanted, and Implantable Cardioverter/Defibrillator (ICD) at Baseline	Number of participants with atrial fibrillation/flutter (rapid, irregular heart rhythm), implanted artificial cardiac pacemaker, and implantable cardioverter-defibrillator (ICD) (detects and stops irregular heartbeats, also called arrhythmias) were reported.	At the start of data collection at Baseline (Day 1)

Collaborators and Investigators

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

Publications and helpful links

General Publications

• Huber P, Flynn A, Sultan MB, Li H, Rill D, Ebede B, Gundapaneni B, Schwartz JH. A comprehensive safety profile of tafamidis in patients with transthyretin amyloid polyneuropathy. Amyloid. 2019 Dec;26(4):203-209. doi: 10.1080/13506129.2019.1643714. Epub 2019 Jul 27.
• Dispenzieri A, Coelho T, Conceicao I, Waddington-Cruz M, Wixner J, Kristen AV, Rapezzi C, Plante-Bordeneuve V, Gonzalez-Moreno J, Maurer MS, Grogan M, Chapman D, Amass L; THAOS investigators. Clinical and genetic profile of patients enrolled in the Transthyretin Amyloidosis Outcomes Survey (THAOS): 14-year update. Orphanet J Rare Dis. 2022 Jun 18;17(1):236. doi: 10.1186/s13023-022-02359-w.
• Campbell CM, LoRusso S, Dispenzieri A, Kristen AV, Maurer MS, Rapezzi C, Lairez O, Drachman B, Garcia-Pavia P, Grogan M, Chapman D, Amass L; THAOS investigators. Sex Differences in Wild-Type Transthyretin Amyloidosis: An Analysis from the Transthyretin Amyloidosis Outcomes Survey (THAOS). Cardiol Ther. 2022 Sep;11(3):393-405. doi: 10.1007/s40119-022-00265-7. Epub 2022 May 18.
• Barroso FA, Coelho T, Dispenzieri A, Conceicao I, Waddington-Cruz M, Wixner J, Maurer MS, Rapezzi C, Plante-Bordeneuve V, Kristen AV, Gonzalez-Duarte A, Chapman D, Stewart M, Amass L; THAOS investigators. Characteristics of patients with autonomic dysfunction in the Transthyretin Amyloidosis Outcomes Survey (THAOS). Amyloid. 2022 Sep;29(3):175-183. doi: 10.1080/13506129.2022.2043270. Epub 2022 Apr 22.
• Nativi-Nicolau J, Siu A, Dispenzieri A, Maurer MS, Rapezzi C, Kristen AV, Garcia-Pavia P, LoRusso S, Waddington-Cruz M, Lairez O, Witteles R, Chapman D, Amass L, Grogan M; THAOS Investigators. Temporal Trends of Wild-Type Transthyretin Amyloid Cardiomyopathy in the Transthyretin Amyloidosis Outcomes Survey. JACC CardioOncol. 2021 Oct 19;3(4):537-546. doi: 10.1016/j.jaccao.2021.08.009. eCollection 2021 Oct.
• Gonzalez-Moreno J, Losada-Lopez I, Cisneros-Barroso E, Garcia-Pavia P, Gonzalez-Costello J, Munoz-Beamud F, Campistol JM, Fernandez-Torron R, Chapman D, Amass L. A Descriptive Analysis of ATTR Amyloidosis in Spain from the Transthyretin Amyloidosis Outcomes Survey. Neurol Ther. 2021 Dec;10(2):833-845. doi: 10.1007/s40120-021-00267-y. Epub 2021 Jul 30.
• Gentile L, Tournev I, Amass L, Chapman D, Mazzeo A; THAOS investigators. Phenotypic Differences of Glu89Gln Genotype in ATTR Amyloidosis From Endemic Loci: Update From THAOS. Cardiol Ther. 2021 Dec;10(2):481-490. doi: 10.1007/s40119-021-00226-6. Epub 2021 Jun 19.
• Waddington-Cruz M, Wixner J, Amass L, Kiszko J, Chapman D, Ando Y; THAOS investigators. Characteristics of Patients with Late- vs. Early-Onset Val30Met Transthyretin Amyloidosis from the Transthyretin Amyloidosis Outcomes Survey (THAOS). Neurol Ther. 2021 Dec;10(2):753-766. doi: 10.1007/s40120-021-00258-z. Epub 2021 May 22.
• Gonzalez-Duarte A, Barroso F, Mundayat R, Shapiro B. Blood pressure and orthostatic hypotension as measures of autonomic dysfunction in patients from the transthyretin amyloidosis outcomes survey (THAOS). Auton Neurosci. 2019 Dec;222:102590. doi: 10.1016/j.autneu.2019.102590. Epub 2019 Oct 23.
• Pinto MV, Pinto LF, Dias M, Rosa RS, Mundayat R, Pedrosa RC, Waddington-Cruz M. Late-onset hereditary ATTR V30M amyloidosis with polyneuropathy: Characterization of Brazilian subjects from the THAOS registry. J Neurol Sci. 2019 Aug 15;403:1-6. doi: 10.1016/j.jns.2019.05.030. Epub 2019 May 28.
• Cruz MW, Pinto MV, Pinto LF, Gervais R, Dias M, Perez C, Mundayat R, Ong ML, Pedrosa RC, Foguel D. Baseline disease characteristics in Brazilian patients enrolled in Transthyretin Amyloidosis Outcome Survey (THAOS). Arq Neuropsiquiatr. 2019 Feb;77(2):96-100. doi: 10.1590/0004-282X20180156.
• Rubin J, Steidley DE, Carlsson M, Ong ML, Maurer MS. Myocardial Contraction Fraction by M-Mode Echocardiography Is Superior to Ejection Fraction in Predicting Mortality in Transthyretin Amyloidosis. J Card Fail. 2018 Aug;24(8):504-511. doi: 10.1016/j.cardfail.2018.07.001. Epub 2018 Aug 17.
• Mundayat R, Stewart M, Alvir J, Short S, Ong ML, Keohane D, Rill D, Sultan MB. Positive Effectiveness of Tafamidis in Delaying Disease Progression in Transthyretin Familial Amyloid Polyneuropathy up to 2 Years: An Analysis from the Transthyretin Amyloidosis Outcomes Survey (THAOS). Neurol Ther. 2018 Jun;7(1):87-101. doi: 10.1007/s40120-018-0097-9. Epub 2018 Apr 9.
• Kristen AV, Maurer MS, Rapezzi C, Mundayat R, Suhr OB, Damy T; THAOS investigators. Impact of genotype and phenotype on cardiac biomarkers in patients with transthyretin amyloidosis - Report from the Transthyretin Amyloidosis Outcome Survey (THAOS). PLoS One. 2017 Apr 6;12(4):e0173086. doi: 10.1371/journal.pone.0173086. eCollection 2017.
• Maurer MS, Hanna M, Grogan M, Dispenzieri A, Witteles R, Drachman B, Judge DP, Lenihan DJ, Gottlieb SS, Shah SJ, Steidley DE, Ventura H, Murali S, Silver MA, Jacoby D, Fedson S, Hummel SL, Kristen AV, Damy T, Plante-Bordeneuve V, Coelho T, Mundayat R, Suhr OB, Waddington Cruz M, Rapezzi C; THAOS Investigators. Genotype and Phenotype of Transthyretin Cardiac Amyloidosis: THAOS (Transthyretin Amyloid Outcome Survey). J Am Coll Cardiol. 2016 Jul 12;68(2):161-72. doi: 10.1016/j.jacc.2016.03.596.
• Damy T, Maurer MS, Rapezzi C, Plante-Bordeneuve V, Karayal ON, Mundayat R, Suhr OB, Kristen AV. Clinical, ECG and echocardiographic clues to the diagnosis of TTR-related cardiomyopathy. Open Heart. 2016 Feb 8;3(1):e000289. doi: 10.1136/openhrt-2015-000289. eCollection 2016.
• Coelho T, Maurer MS, Suhr OB. THAOS - The Transthyretin Amyloidosis Outcomes Survey: initial report on clinical manifestations in patients with hereditary and wild-type transthyretin amyloidosis. Curr Med Res Opin. 2013 Jan;29(1):63-76. doi: 10.1185/03007995.2012.754348. Epub 2012 Dec 13.
• Coelho T, Conceicao I, Waddington-Cruz M, Keohane D, Sultan MB, Chapman D, Amass L; THAOS investigators. A natural history analysis of asymptomatic TTR gene carriers as they develop symptomatic transthyretin amyloidosis in the Transthyretin Amyloidosis Outcomes Survey (THAOS). Amyloid. 2022 Dec;29(4):228-236. doi: 10.1080/13506129.2022.2070470. Epub 2022 Jun 22.
• Damy T, Kristen AV, Suhr OB, Maurer MS, Plante-Bordeneuve V, Yu CR, Ong ML, Coelho T, Rapezzi C; THAOS Investigators. Transthyretin cardiac amyloidosis in continental Western Europe: an insight through the Transthyretin Amyloidosis Outcomes Survey (THAOS). Eur Heart J. 2022 Feb 3;43(5):391-400. doi: 10.1093/eurheartj/ehz173.

Helpful Links

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

Study record dates

Study Major Dates

• Study Start (Actual): January 4, 2008
• Primary Completion (Actual): June 16, 2023
• Study Completion (Actual): June 19, 2023

Study Registration Dates

• First Submitted: February 25, 2008
• First Submitted That Met QC Criteria: March 4, 2008
• First Posted (Estimated): March 5, 2008

Study Record Updates

• Last Update Posted (Actual): November 22, 2024
• Last Update Submitted That Met QC Criteria: October 1, 2024
• Last Verified: October 1, 2024

More Information

Terms related to this study

• Keywords: Transthyretin amyloid cardiomyopathy; TRANSTHYRETIN; AMYLOIDOSIS; TRANSTHYRETIN AMYLOIDOSIS
• Additional Relevant MeSH Terms: Nervous System Diseases; Neuromuscular Diseases; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Metabolic Diseases; Peripheral Nervous System Diseases; Neurodegenerative Diseases; Heredodegenerative Disorders, Nervous System; Proteostasis Deficiencies; Amyloid Neuropathies; Amyloidosis, Familial; Amyloidosis; Amyloid Neuropathies, Familial
• Other Study ID Numbers: B3461001; FX-R-001 (Other Identifier: Alias Study Number); THAOS (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: Yes
• Studies a U.S. FDA-regulated device product: No