Transthyretin Amyloidosis Outcome Survey (THAOS)
- Conditions
- Transthyretin Gene MutationsTransthyretin Amyloidosis
- Interventions
- Other: None. Observational Study.
- Registration Number
- NCT00628745
- Lead Sponsor
- Pfizer
- Brief Summary
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.
- Detailed Description
n/a NA
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 6718
Patients must meet all of the following inclusion criteria to be eligible for inclusion into THAOS:
-
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.
-
Males and females greater than or equal to 18 years of age.
-
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):
- Presence of amyloid in cardiac biopsy tissue confirmed as TTR amyloid by mass spectrometry or immunohistochemistry; or
- 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
- 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:
- Patient has evidence of primary (light chain) or secondary amyloidosis.
Not provided
Study & Design
- Study Type
- OBSERVATIONAL
- Study Design
- Not specified
- Arm && Interventions
Group Intervention Description Observational None. Observational Study. -
- Primary Outcome Measures
Name Time Method Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) From the start of data collection at Baseline (Day 1) to the end of data collection (Up to 14.4 years) 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.
Number of Participants With Treatment Emergent Treatment Related AEs and SAEs From the start of data collection at Baseline (Day 1) to the end of data collection (Up to 14.4 years) 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.
Number of All-Cause Deaths From the start of data collection at Baseline (Day 1) to the end of data collection (Up to 14.4 years) Number of deaths due to any cause was analyzed as time from enrollment or first treatment of tafamidis.
- Secondary Outcome Measures
Name Time Method Number of Participants With Modified Polyneuropathy Disability (mPND) Scores at Baseline At the start of data collection at Baseline (Day 1) 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.
Number of Participants With Coutinho Disease Stages at Baseline At the start of data collection at Baseline (Day 1) 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.
Number of Participants With Karnofsky Performance Index at Baseline At the start of data collection at Baseline (Day 1) 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.
Number of Participants With Heart Failure at Baseline At the start of data collection at Baseline (Day 1) Heart failure, also known as congestive heart failure is a cardiovascular event.
Number of Participants With New York Heart Association (NYHA) Classifications at Baseline At the start of data collection at Baseline (Day 1) 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).
Number of Participants Diagnosed With ATTR at Baseline At the start of data collection at Baseline (Day 1) Participants diagnosed with Transthyretin Amyloidosis (ATTR) at baseline with assessed category of yes, no, and unknown.
Number of Participants With Prior Misdiagnosis at Baseline At the start of data collection at Baseline (Day 1) Number of participants with ATTR and participants who had prior misdiagnosis at the baseline were reported.
Number of Participants With ATTR Genotypes at Baseline At the start of data collection at Baseline (Day 1) 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.
Number of Participants With Past or Current Clinical Trial Participation at Baseline At the start of data collection at Baseline (Day 1) Number of participants had previous or current participant in any clinical trials at the baseline.
Number of Participants With Past or Current Tafamidis Compassionate Use/Early Access or Other Non-commercial Program at Baseline At the start of data collection at Baseline (Day 1) 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.
Number of Participants With Known Family History of Symptomatic ATTR at Baseline At the start of data collection at Baseline (Day 1) Number of participants whether with family history of symptomatic ATTR amyloidosis at Baseline were reported.
Number of Affected Generations at Baseline At the start of data collection at Baseline (Day 1) The mean of affected generations in participants with a known family history was reported.
Derived Neuropathy Impairment Score-Lower Limb (NIS-LL) at Baseline At the start of data collection at Baseline (Day 1) 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.
Body Mass Index (BMI) at Baseline At the start of data collection at Baseline (Day 1) BMI was calculated by weight divided by height squared and measured as kilogram per square meter (kg/m\^2).
Modified Body Mass Index (mBMI) at Baseline At the start of data collection at Baseline (Day 1) 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.
Sitting Systolic and Diastolic Blood Pressures (SBP and DBP) at Baseline At the start of data collection at Baseline (Day 1) 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.
Left Ventricular (LV) Septum Thickness at Baseline At the start of data collection at Baseline (Day 1) 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.
Left Ventricular (LV) Ejection Fraction at Baseline At the start of data collection at Baseline (Day 1) 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.
Euro Quality of Life-5 Dimensions-3 Level (EQ-5D-3L): Visual Analog Scale (VAS) Overall Health Score at Baseline At the start of data collection at Baseline (Day 1) 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.
EQ-5D-3L: VAS Derived Index at Baseline At the start of data collection at Baseline (Day 1) 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.
Norfolk Total Quality of Life (QoL) Score at Baseline At the start of data collection at Baseline (Day 1) 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.
Number of Participants With Abnormal Electrocardiogram (ECG) at Baseline At the start of data collection at Baseline (Day 1) 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.
Number of Participants With Atrial Fibrillation/Flutter, Pacemaker Implanted, and Implantable Cardioverter/Defibrillator (ICD) at Baseline At the start of data collection at Baseline (Day 1) 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.
Trial Locations
- Locations (112)
The University of Utah Health Sciences Center
🇺🇸Salt Lake City, Utah, United States
Medical College of Wisconsin
🇺🇸Milwaukee, Wisconsin, United States
Hospital Italiano de Buenos Aires (HIBA)
🇦🇷Buenos Aires, Argentina
FLENI
🇦🇷Ciudad Autonoma de Buenos aires, Argentina
Instituto De Investigaciones Medicas Dr Alfredo Lanari
🇦🇷Ciudad Autonoma De Buenos Aires, Argentina
Afdeling Klinische Cardiologie, O&N I
🇧🇪Leuven, Belgium
Hospital Universitário Clementino Fraga Filho -HUCFF Universidade Federal do Rio de Janeiro
🇧🇷Rio de Janeiro, Brazil
Instituto Dante Pazzanese De Cardiologia
🇧🇷Sao Paulo, Brazil
Alexandrovska University Hospital Clinic of Neurology
🇧🇬Sofia, Bulgaria
University of Alberta Foothills Medical Centre
🇨🇦Calgary, Alberta, Canada
Toronto General Hospital-University Health Network
🇨🇦Toronto, Ontario, Canada
Toronto General Hospital
🇨🇦Toronto, Ontario, Canada
Cyprus Institute of Neurology and Genetics
🇨🇾Nicosia, Cyprus
Aarhus University Hospital, Skejby
🇩🇰Aarhus, Denmark
CHU de Bicetre
🇫🇷Cedex, France
Hopital Louis Pasteur
🇫🇷Colmar, France
CHU Henri Mondor
🇫🇷Créteil, France
Chu De Fort De France
🇫🇷Fort De France, France
CHRU de Lille, Hopital Claude Huriez
🇫🇷Lille, France
Hopital Salengro - CHRU de Lille
🇫🇷Lille, France
CHU de Toulouse - Hopital Rangueil
🇫🇷Toulouse cedex 09, France
University Hospital of RWTH Aachen
🇩🇪Aachen, Germany
Charite CAmpus Rudolf-Virchow-Klinikum
🇩🇪Berlin, Germany
Medical University of Heidelberg
🇩🇪Heidelberg, Germany
Johann-Gutenberg-Universität
🇩🇪Mainz, Germany
University Medical Center, Johannes Gutenberg-University Mainz
🇩🇪Mainz, Germany
Universitätsmedizin der Johannes Gutenberg Universität Mainz KöR
🇩🇪Mainz, Germany
Universitatsklinikum Muenster - Transplant Hepatology
🇩🇪Muenster, Germany
Wolfson Medical Center
🇮🇱Holon, Israel
Fondazione Policlinico Gemelli - Universita Cattolica del Sacro Cuore
🇮🇹Roma, Italy
Sheba Medical Center
🇮🇱Ramat Gan, Israel
Comitato Etico Indipendente dell Azienda
🇮🇹Bologna, Italy
Azienda Ospedaliero-Universitaria di Careggi
🇮🇹Firenze, Italy
AOU Policlinico G. Martino - Messina - Comitato Etico Scientifico
🇮🇹Messina, Italy
AOU Policlinico G. Martino - Messina - Dr. Vita
🇮🇹Messina, Italy
Centro per lo Studio e la Cura delle Amiloidosi Sistemiche - Pavia - Prof. Merlini
🇮🇹Pavia, Italy
Comitato di Bioetica della Fondazione IRCCS Policlinico S. Matteo
🇮🇹Pavia, Italy
Fondazione Toscana Gabriele Monasterio Per La Ricerca Medica E Di Sanita Pubblica (Ftgm)
🇮🇹Pisa, Italy
Shinshu University School of Medicine
🇯🇵Matsumoto, JP, Japan
Chiba University Hospital
🇯🇵Chiba, Japan
Kumamoto University
🇯🇵Kumamoto, Japan
Samsung Medical Center, Sungkyunkwan University School of Medicine
🇰🇷Seoul, Korea, Republic of
Konkuk University Medical Center
🇰🇷Seoul, Korea, Republic of
University Malaya Medical Centre (UMMC)
🇲🇾Kuala Lumpur, Wilayah Persekutuan, Malaysia
Instituto Nacional de Ciencia Medicas y Nutricion Salvador Zubiran
🇲🇽Distrito Federal, Mexico
University Medical Center Groningen
🇳🇱Groningen, Netherlands
Centro Hospitalar Do Alto Ave, Epe
🇵🇹Guimaraes, Portugal
Centro Hospitalar Lisboa Norte (CHLN) EPE - Hospital de Santa Maria
🇵🇹Lisboa, Portugal
Hospital Santa Maria
🇵🇹Lisboa, Portugal
Unidade Clinica de Paramiloidose-Centro Hospitalar Porto,EPE-Hospital Geral Santo Antonio
🇵🇹Porto, Portugal
Institutul De Cardiologie Prof. Dr. C. C. Iliescu Spitalului Fundeni
🇷🇴Bucuresti, Romania
King Faisal Specialist Hospital and Research Center
🇸🇦Riyadh, Saudi Arabia
Hospital Universitario Donostia
🇪🇸Gipuzkoa - SanSebastian, Donostia, Spain
Hospital Universitario Puerta de Hierro
🇪🇸Majadahonda, Madrid, Spain
Institut Clinic de Nefrologia i Urologia - ICNU, Hospital Clinic i Provincial de Barcelona
🇪🇸Barcelona, Spain
Hospital Universitari de Bellvitge
🇪🇸Barcelona, Spain
Hospital de Rehabilitacion y Traumatologia Virgen de las Nieves
🇪🇸Granada, Spain
Hospital Juan Ramon Jimenez
🇪🇸Huelva, Spain
Hospital Gregorio Marañón
🇪🇸Madrid, Spain
Hospital Clinico San Carlos
🇪🇸Madrid, Spain
Piteå Älvdals Hospital
🇸🇪Piteå, Sweden
Karolinska University Hospital, Huddinge
🇸🇪Stockholm, Sweden
Umeå University Hospital
🇸🇪Umeå, Sweden
National Taiwan University Hospital
🇨🇳Taipei, Taiwan
Istanbul University,Istanbul Faculty of Medicine,Department of Neurology
🇹🇷Istanbul, Turkey
Cleveland Clinic Abu Dhabi LLC
🇦🇪Abu Dhabi, United Arab Emirates
Johns Hopkins Hospital
🇺🇸Baltimore, Maryland, United States
Harvard Vanguard Medical Associates
🇺🇸Boston, Massachusetts, United States
University of Michigan
🇺🇸Ann Arbor, Michigan, United States
Mayo Clinic
🇺🇸Rochester, Minnesota, United States
Washington University School of Medicine
🇺🇸Saint Louis, Missouri, United States
Cardiology Clinic at Montefiore Hutchinson Campus
🇺🇸Bronx, New York, United States
Montefiore Medical Center-Jack D. Weiler Hospital
🇺🇸Bronx, New York, United States
Congestive Heart Failure Clinic
🇺🇸Bronx, New York, United States
Montefiore Moses Division
🇺🇸Bronx, New York, United States
NYU Medical Center
🇺🇸New York, New York, United States
Columbia University Medical Center
🇺🇸New York, New York, United States
Cleveland Clinic Foundation
🇺🇸Cleveland, Ohio, United States
The Ohio University College of Medicine
🇺🇸Columbus, Ohio, United States
OSU Wexner Medical Center
🇺🇸Columbus, Ohio, United States
Oregon Health and Science University
🇺🇸Portland, Oregon, United States
Peters Township Health and Wellness Pavillion
🇺🇸McMurray, Pennsylvania, United States
Penn Presbyterian Medical Center-University of Pennsylvania
🇺🇸Philadelphia, Pennsylvania, United States
University of Pennsylvania - Perelman Center for Advanced Medicine
🇺🇸Philadelphia, Pennsylvania, United States
Temple University School of Medicine
🇺🇸Philadelphia, Pennsylvania, United States
Allegheny General Hospital
🇺🇸Pittsburgh, Pennsylvania, United States
Admin
🇺🇸Pittsburgh, Pennsylvania, United States
University of Pittsburgh Medical Center (UPMC)
🇺🇸Pittsburgh, Pennsylvania, United States
Wexford Health and Wellness Pavillion
🇺🇸Wexford, Pennsylvania, United States
IRB
🇺🇸Nashville, Tennessee, United States
Vanderbilt University School of Medicine
🇺🇸Nashville, Tennessee, United States
University of Maryland
🇺🇸Baltimore, Maryland, United States
Hospital Son Llàtzer
🇪🇸Palma de Mallorca, Spain
University of Alabama at Birmingham
🇺🇸Birmingham, Alabama, United States
Mayo Clinic Arizona
🇺🇸Phoenix, Arizona, United States
VA Greater Los Angeles Healthcare System
🇺🇸Los Angeles, California, United States
University of California, Irvine
🇺🇸Orange, California, United States
University of California - San Francisco, UCSF Department of Neurology
🇺🇸San Francisco, California, United States
Office of Sponsored Research
🇺🇸San Francisco, California, United States
Stanford University School of Medicine
🇺🇸Stanford, California, United States
UC Denver
🇺🇸Aurora, Colorado, United States
Smilow Cancer Hospital at Yale-New Haven
🇺🇸New Haven, Connecticut, United States
UHealth Deerfield Beach
🇺🇸Deerfield Beach, Florida, United States
University of Miami Hospital & Clinics
🇺🇸Miami, Florida, United States
UHealth Plantation
🇺🇸Plantation, Florida, United States
Clinical Trials Unit
🇺🇸Chicago, Illinois, United States
Northwestern University
🇺🇸Chicago, Illinois, United States
University of Chicago Medical Center IRB
🇺🇸Chicago, Illinois, United States
University of Chicago Medical Center
🇺🇸Chicago, Illinois, United States
Advocate Christ Medical Centre
🇺🇸Oak Lawn, Illinois, United States
John Ochsner Heart & Vascular Institute
🇺🇸New Orleans, Louisiana, United States
University of Maryland School of Medicine
🇺🇸Baltimore, Maryland, United States