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.
Brief Title
Transthyretin Amyloidosis Outcome Survey (THAOS)
Detailed Description
n/a NA
Categories
Completion Date
Completion Date Type
Actual
Conditions
Transthyretin Gene Mutations
Transthyretin Amyloidosis
Eligibility Criteria
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.
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.
Inclusion Criteria
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.
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.
Gender
All
Gender Based
false
Keywords
TRANSTHYRETIN
AMYLOIDOSIS
TRANSTHYRETIN AMYLOIDOSIS
Transthyretin amyloid cardiomyopathy
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Minimum Age
18 Years
NCT Id
NCT00628745
Org Class
Industry
Org Full Name
Pfizer
Org Study Id
B3461001
Overall Status
Completed
Primary Completion Date
Primary Completion Date Type
Actual
Official Title
Transthyretin Amyloidosis Outcomes Survey (THAOS): A Global, Multi-Center, Longitudinal, Observational Survey of Patients With Documented Transthyretin Gene Mutations or Wild-Type Transthyretin Amyloidosis.
Primary Outcomes
Outcome Description
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.
Outcome Measure
Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
Outcome Time Frame
From the start of data collection at Baseline (Day 1) to the end of data collection (Up to 14.4 years)
Outcome Description
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.
Outcome Measure
Number of Participants With Treatment Emergent Treatment Related AEs and SAEs
Outcome Time Frame
From the start of data collection at Baseline (Day 1) to the end of data collection (Up to 14.4 years)
Outcome Description
Number of deaths due to any cause was analyzed as time from enrollment or first treatment of tafamidis.
Outcome Measure
Number of All-Cause Deaths
Outcome Time Frame
From the start of data collection at Baseline (Day 1) to the end of data collection (Up to 14.4 years)
Secondary Ids
Secondary Id
FX-R-001
Secondary Id
THAOS
Secondary Outcomes
Outcome Description
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.
Outcome Time Frame
At the start of data collection at Baseline (Day 1)
Outcome Measure
Number of Participants With Modified Polyneuropathy Disability (mPND) Scores at Baseline
Outcome Description
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.
Outcome Time Frame
At the start of data collection at Baseline (Day 1)
Outcome Measure
Number of Participants With Coutinho Disease Stages at Baseline
Outcome Description
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.
Outcome Time Frame
At the start of data collection at Baseline (Day 1)
Outcome Measure
Number of Participants With Karnofsky Performance Index at Baseline
Outcome Description
Heart failure, also known as congestive heart failure is a cardiovascular event.
Outcome Time Frame
At the start of data collection at Baseline (Day 1)
Outcome Measure
Number of Participants With Heart Failure at Baseline
Outcome Description
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).
Outcome Time Frame
At the start of data collection at Baseline (Day 1)
Outcome Measure
Number of Participants With New York Heart Association (NYHA) Classifications at Baseline
Outcome Description
Participants diagnosed with Transthyretin Amyloidosis (ATTR) at baseline with assessed category of yes, no, and unknown.
Outcome Time Frame
At the start of data collection at Baseline (Day 1)
Outcome Measure
Number of Participants Diagnosed With ATTR at Baseline
Outcome Description
Number of participants with ATTR and participants who had prior misdiagnosis at the baseline were reported.
Outcome Time Frame
At the start of data collection at Baseline (Day 1)
Outcome Measure
Number of Participants With Prior Misdiagnosis at Baseline
Outcome Description
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.
Outcome Time Frame
At the start of data collection at Baseline (Day 1)
Outcome Measure
Number of Participants With ATTR Genotypes at Baseline
Outcome Description
Number of participants had previous or current participant in any clinical trials at the baseline.
Outcome Time Frame
At the start of data collection at Baseline (Day 1)
Outcome Measure
Number of Participants With Past or Current Clinical Trial Participation at Baseline
Outcome Description
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.
Outcome Time Frame
At the start of data collection at Baseline (Day 1)
Outcome Measure
Number of Participants With Past or Current Tafamidis Compassionate Use/Early Access or Other Non-commercial Program at Baseline
Outcome Description
Number of participants whether with family history of symptomatic ATTR amyloidosis at Baseline were reported.
Outcome Time Frame
At the start of data collection at Baseline (Day 1)
Outcome Measure
Number of Participants With Known Family History of Symptomatic ATTR at Baseline
Outcome Description
The mean of affected generations in participants with a known family history was reported.
Outcome Time Frame
At the start of data collection at Baseline (Day 1)
Outcome Measure
Number of Affected Generations at Baseline
Outcome Description
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.
Outcome Time Frame
At the start of data collection at Baseline (Day 1)
Outcome Measure
Derived Neuropathy Impairment Score-Lower Limb (NIS-LL) at Baseline
Outcome Description
BMI was calculated by weight divided by height squared and measured as kilogram per square meter (kg/m\^2).
Outcome Time Frame
At the start of data collection at Baseline (Day 1)
Outcome Measure
Body Mass Index (BMI) at Baseline
Outcome Description
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.
Outcome Time Frame
At the start of data collection at Baseline (Day 1)
Outcome Measure
Modified Body Mass Index (mBMI) at Baseline
Outcome Description
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.
Outcome Time Frame
At the start of data collection at Baseline (Day 1)
Outcome Measure
Sitting Systolic and Diastolic Blood Pressures (SBP and DBP) at Baseline
Outcome Description
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.
Outcome Time Frame
At the start of data collection at Baseline (Day 1)
Outcome Measure
Left Ventricular (LV) Septum Thickness at Baseline
Outcome Description
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.
Outcome Time Frame
At the start of data collection at Baseline (Day 1)
Outcome Measure
Left Ventricular (LV) Ejection Fraction at Baseline
Outcome Description
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.
Outcome Time Frame
At the start of data collection at Baseline (Day 1)
Outcome Measure
Euro Quality of Life-5 Dimensions-3 Level (EQ-5D-3L): Visual Analog Scale (VAS) Overall Health Score at Baseline
Outcome Description
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.
Outcome Time Frame
At the start of data collection at Baseline (Day 1)
Outcome Measure
EQ-5D-3L: VAS Derived Index at Baseline
Outcome Description
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.
Outcome Time Frame
At the start of data collection at Baseline (Day 1)
Outcome Measure
Norfolk Total Quality of Life (QoL) Score at Baseline
Outcome Description
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.
Outcome Time Frame
At the start of data collection at Baseline (Day 1)
Outcome Measure
Number of Participants With Abnormal Electrocardiogram (ECG) at Baseline
Outcome Description
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.
Outcome Time Frame
At the start of data collection at Baseline (Day 1)
Outcome Measure
Number of Participants With Atrial Fibrillation/Flutter, Pacemaker Implanted, and Implantable Cardioverter/Defibrillator (ICD) at Baseline
See Also Links
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Estimated
First Submit Date
First Submit QC Date
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.
Std Ages
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
999
Minimum Age Number (converted to Years and rounded down)
18
Investigators
Investigator Type
Principal Investigator
Investigator Name
James Tauras
Investigator Email
jtauras@montefiore.org
Investigator Phone