An observational study in Transthyretin Gene Mutations and Transthyretin Amyloidosis, sponsored by Pfizer. Completed at 113 sites in 25 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2024-11-22.
Sponsored by Pfizer · Observational
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.
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42 studies on the registry are indexed under Amyloidosis, Hereditary, Transthyretin-Related; 22 are open to participants now.
This study's enrollment of 6,718 is above the median of 261 across 20 observational studies indexed under Amyloidosis, Hereditary, Transthyretin-Related.
Browse Amyloidosis, Hereditary, Transthyretin-Related studies →Pfizer is the lead sponsor of 3,323 studies on the registry; 145 are open to participants now.
Of its 597 completed or terminated interventional studies of FDA-regulated products, 391 (65%) have results posted.
Counted across the registry records on this site, refreshed daily.
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.
Inclusion Criteria: Patients must meet all of the following inclusion criteria to be eligible for inclusion into THAOS:
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):
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.
Other: None. Observational Study.
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.
Time frame: 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.
Time frame: 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.
Time frame: 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 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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).
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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).
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: At the start of data collection at Baseline (Day 1)
THAOS (Transthyretin Amyloidosis Outcome Survey) was a non-interventional, longitudinal observational survey opened to all participants with ATTR (Transthyretin Amyloidosis), including both inherited and wild-type forms of disease and those with TTR gene mutations without disease diagnosis. There was no planned enroll number. THAOS did not involve the administration of an intervention. Participants continued to receive their previous medications and all other standard care for their disease.
| Milestone | Tafamidis 20 mg Treated | Tafamidis 61/80 mg Treated-Overall | Tafamidis 20 mg to 61/80 mg Treated-Overall | Tafamidis Other Treated-Overall | Tafamidis Untreated |
|---|---|---|---|---|---|
| Started | 1648 | 662 | 196 | 15 | 4197 |
| Completed | 4 | 0 | 1 | 0 | 8 |
| Not completed | 1644 | 662 | 195 | 15 | 4189 |
| Withdrew: Withdrawal by subject | 63 | 3 | 9 | 2 | 69 |
| Withdrew: Does not meet inclusion criteria | 0 | 12 | 0 | 0 | 18 |
| Withdrew: Participation in an interventional clinical trial | 81 | 4 | 7 | 0 | 63 |
| Withdrew: Physician decision | 8 | 4 | 3 | 0 | 30 |
| Withdrew: Lost to follow-up | 109 | 7 | 7 | 0 | 498 |
| Withdrew: Death | 197 | 81 | 12 | 4 | 939 |
| Withdrew: Participant transferred to another thaos site | 6 | 0 | 0 | 0 | 7 |
| Withdrew: Participant moved out of the area, but did not transfer to another thaos site | 37 | 29 | 46 | 0 | 91 |
| Withdrew: Site closure | 152 | 146 | 6 | 8 | 691 |
| Withdrew: Duplicate participant | 0 | 0 | 0 | 0 | 1 |
| Withdrew: Missing | 4 | 3 | 0 | 0 | 10 |
| Withdrew: Othe reasons | 987 | 373 | 105 | 1 | 1772 |
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.
| Participants | Tafamidis 20 mg Treated-Overall | Tafamidis 61/80 mg Treated-Overall | Tafamidis 20 mg to 61/80 mg Treated-Overall | Tafamidis Other Treated-Overall |
|---|---|---|---|---|
| Participants with Adverse Events | 621 | 175 | 66 | 4 |
| Participants with Serious Adverse Events | 331 | 138 | 41 | 3 |
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.
| Participants | Tafamidis 20 mg Treated-Overall | Tafamidis 61/80 mg Treated-Overall | Tafamidis 20 mg to 61/80 mg Treated-Overall | Tafamidis Other Treated-Overall |
|---|---|---|---|---|
| Participants with Adverse Events | 47 | 11 | 1 | 2 |
| Participants with Serious Adverse Events | 28 | 5 | 0 | 1 |
Number of deaths due to any cause was analyzed as time from enrollment or first treatment of tafamidis.
| Participants | Tafamidis Treated-Overall | Tafamidis Untreated-Overall |
|---|---|---|
| Number of All-Cause Deaths | 158 | 1038 |
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.
| Participants | Overall | Tafamidis Treated-Overall | Tafamidis Untreated-Overall |
|---|---|---|---|
| 0 | 1860 | 512 | 1731 |
| I | 1642 | 785 | 1372 |
| II | 492 | 255 | 349 |
| IIIa | 226 | 84 | 160 |
| IIIb | 136 | 37 | 106 |
| IV | 78 | 16 | 67 |
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.
| Participants | Overall | Tafamidis Treated-Overall | Tafamidis Untreated-Overall |
|---|---|---|---|
| Stage 0 | 1860 | 512 | 1731 |
| Stage 1 | 2134 | 1040 | 1721 |
| Stage 2 | 362 | 121 | 266 |
| Stage 3 | 78 | 16 | 67 |
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.
| Participants | Overall | Tafamidis Treated-Overall | Tafamidis Untreated-Overall |
|---|---|---|---|
| 10 | 2 | 1 | 2 |
| 20 | 6 | 0 | 6 |
| 30 | 6 | 3 | 3 |
| 40 | 82 | 15 | 71 |
| 50 | 140 | 31 | 121 |
| 60 | 271 | 92 | 209 |
| 70 | 492 | 200 | 375 |
| 80 | 944 | 436 | 728 |
| 90 | 1127 | 633 | 890 |
| 100 | 1694 | 484 | 1593 |
Heart failure, also known as congestive heart failure is a cardiovascular event.
| Participants | Overall | Tafamidis Treated-Overall | Tafamidis Untreated-Overall |
|---|---|---|---|
| Number of Participants With Heart Failure at Baseline | 2717 | 1125 | 2245 |
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).
| Participants | Overall | Tafamidis Treated-Overall | Tafamidis Untreated-Overall |
|---|---|---|---|
| I | 304 | 133 | 252 |
| II | 1341 | 557 | 1088 |
| III | 664 | 222 | 556 |
| IV | 71 | 10 | 67 |
Participants diagnosed with Transthyretin Amyloidosis (ATTR) at baseline with assessed category of yes, no, and unknown.
| Participants | Overall | Tafamidis Treated-Overall | Tafamidis Untreated-Overall |
|---|---|---|---|
| Yes | 4773 | 2368 | 3794 |
| No | 1234 | 36 | 1227 |
| Unknown | 28 | 4 | 25 |
Number of participants with ATTR and participants who had prior misdiagnosis at the baseline were reported.
| Participants | Overall | Tafamidis Treated-Overall | Tafamidis Untreated-Overall |
|---|---|---|---|
| Number of Participants With Prior Misdiagnosis at Baseline | 616 | 283 | 493 |
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.
| Participants | Overall | Tafamidis Treated-Overall | Tafamidis Untreated-Overall |
|---|---|---|---|
| ATTRv mutation | 4950 | 1743 | 4365 |
| Wild type | 1768 | 778 | 1321 |
Number of participants had previous or current participant in any clinical trials at the baseline.
| Participants | Overall | Tafamidis Treated-Overall | Tafamidis Untreated-Overall |
|---|---|---|---|
| Yes | 853 | 473 | 669 |
| No | 4417 | 1676 | 3604 |
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.
| Participants | Overall | Tafamidis Treated-Overall | Tafamidis Untreated-Overall |
|---|---|---|---|
| Yes | 85 | 80 | 38 |
| No | 3182 | 1410 | 2423 |
Number of participants whether with family history of symptomatic ATTR amyloidosis at Baseline were reported.
| Participants | Overall | Tafamidis Treated-Overall | Tafamidis Untreated-Overall |
|---|---|---|---|
| Yes | 3874 | 1365 | 3485 |
| No | 2243 | 873 | 1792 |
| Unknown | 559 | 275 | 375 |
The mean of affected generations in participants with a known family history was reported.
| Generation | Overall | Tafamidis Treated-Overall | Tafamidis Untreated-Overall |
|---|---|---|---|
| Number of Affected Generations at Baseline | 1.5 ± 0.95 | 1.5 ± 1.01 | 1.5 ± 0.96 |
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.
| Score on a scale | Overall | Tafamidis Treated-Overall | Tafamidis Untreated-Overall |
|---|---|---|---|
| Derived NIS-LL Score | 14.0 ± 20.73 | 20.3 ± 20.17 | 12.7 ± 20.14 |
| Reflex Score | 8.2 ± 3.05 | 7.5 ± 3.13 | 8.3 ± 2.94 |
| Motor Score | 152.2 ± 19.11 | 150.6 ± 18.98 | 152.8 ± 18.41 |
| Sensory Score | 108.2 ± 25.83 | 97.6 ± 26.79 | 109.4 ± 25.19 |
BMI was calculated by weight divided by height squared and measured as kilogram per square meter (kg/m\^2).
| kg/m^2 | Overall | Tafamidis Treated-Overall | Tafamidis Untreated-Overall |
|---|---|---|---|
| Body Mass Index (BMI) at Baseline | 26.3 ± 17.93 | 26.5 ± 24.14 | 25.9 ± 11.12 |
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.
| (kg/m^2)*(g/L) | Overall | Tafamidis Treated-Overall | Tafamidis Untreated-Overall |
|---|---|---|---|
| Modified Body Mass Index (mBMI) at Baseline | 1078 ± 240.9 | 1063.1 ± 228.8 | 1083.3 ± 242.4 |
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.
| mmHg | Overall | Tafamidis Treated-Overall | Tafamidis Untreated-Overall |
|---|---|---|---|
| Sitting Systolic BP (mmHg) | 123.7 ± 18.67 | 125.3 ± 18.78 | 122.9 ± 18.15 |
| Sitting Diastolic BP (mmHg) | 75.3 ± 11.69 | 75.6 ± 11.56 | 75.1 ± 11.58 |
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.
| mm | Overall | Tafamidis Treated-Overall | Tafamidis Untreated-Overall |
|---|---|---|---|
| Left Ventricular (LV) Septum Thickness at Baseline | 15.2 ± 5.27 | 15.3 ± 4.31 | 15.2 ± 5.52 |
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.
| Percentage | Overall | Tafamidis Treated-Overall | Tafamidis Untreated-Overall |
|---|---|---|---|
| Left Ventricular (LV) Ejection Fraction at Baseline | 53.6 ± 13.46 | 54.3 ± 12.61 | 53.5 ± 13.77 |
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.
| Score on a scale | Overall | Tafamidis Treated-Overall | Tafamidis Untreated-Overall |
|---|---|---|---|
| Euro Quality of Life-5 Dimensions-3 Level (EQ-5D-3L): Visual Analog Scale (VAS) Overall Health Score at Baseline | 71.0 ± 20.80 | 70.2 ± 20.01 | 71.7 ± 20.98 |
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.
| Score on a scale | Overall | Tafamidis Treated-Overall | Tafamidis Untreated-Overall |
|---|---|---|---|
| EQ-5D-3L: VAS Derived Index at Baseline | 0.8 ± 0.20 | 0.8 ± 0.19 | 0.8 ± 0.20 |
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.
| Score on a scale | Overall | Tafamidis Treated-Overall | Tafamidis Untreated-Overall |
|---|---|---|---|
| Norfolk Total Quality of Life (QoL) Score at Baseline | 24.3 ± 28.10 | 25.2 ± 27.30 | 23.1 ± 27.90 |
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.
| Participants | Overall | Tafamidis Treated-Overall | Tafamidis Untreated-Overall |
|---|---|---|---|
| Number of Participants With Abnormal Electrocardiogram (ECG) at Baseline | 2911 | 1226 | 2315 |
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.
| Participants | Overall | Tafamidis Treated-Overall | Tafamidis Untreated-Overall |
|---|---|---|---|
| Atrial Fibrillation/Flutter | 667 | 290 | 501 |
| Pacemaker Implanted | 364 | 167 | 266 |
| ICD Implanted | 127 | 62 | 99 |
Collected over From the start of data collection at Baseline (Day 1) to the end of data collection (Up to 14.4 years). Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Tafamidis 20 mg Treated-Overall | 197/1,648 (12%) | 333/1,648 (20.2%) | 94/1,648 (5.7%) |
| Tafamidis 61/80 mg Treated-Overall | 81/662 (12.2%) | 138/662 (20.8%) | 3/662 (0.5%) |
| Tafamidis 20 mg to 61/80 mg Treated-Overall | 12/196 (6.1%) | 41/196 (20.9%) | 0/196 (0%) |
| Tafamidis Other Treated-Overall | 4/15 (26.7%) | 3/15 (20%) | 1/15 (6.7%) |
| Tafamidis Untreated | 939/4,197 (22.4%) | 4/4,197 (0.1%) | 0/4,197 (0%) |
| Event | Tafamidis 20 mg Treated-Overall | Tafamidis 61/80 mg Treated-Overall | Tafamidis 20 mg to 61/80 mg Treated-Overall | Tafamidis Other Treated-Overall | Tafamidis Untreated |
|---|---|---|---|---|---|
| Cardiac failureCardiac disorders | 34/1648 | 32/662 | 18/196 | 0/15 | 1/4197 |
| Cardiac failure congestiveCardiac disorders | 15/1648 | 14/662 | 1/196 | 1/15 | 0/4197 |
| DeathGeneral disorders | 8/1648 | 11/662 | 4/196 | 1/15 | 1/4197 |
| SyncopeNervous system disorders | 8/1648 | 5/662 | 2/196 | 1/15 | 0/4197 |
| DepressionPsychiatric disorders | 1/1648 | 0/662 | 1/196 | 1/15 | 0/4197 |
| Pleural effusionRespiratory, thoracic and mediastinal disorders | 3/1648 | 2/662 | 4/196 | 0/15 | 0/4197 |
| Acute kidney injuryRenal and urinary disorders | 5/1648 | 12/662 | 3/196 | 0/15 | 0/4197 |
| Atrial fibrillationCardiac disorders | 4/1648 | 7/662 | 3/196 | 0/15 | 0/4197 |
| Cardiac arrestCardiac disorders | 6/1648 | 8/662 | 0/196 | 0/15 | 0/4197 |
| Atrial flutterCardiac disorders | 2/1648 | 1/662 | 2/196 | 0/15 | 0/4197 |
| Event | Tafamidis 20 mg Treated-Overall | Tafamidis 61/80 mg Treated-Overall | Tafamidis 20 mg to 61/80 mg Treated-Overall | Tafamidis Other Treated-Overall | Tafamidis Untreated |
|---|---|---|---|---|---|
| Urinary tract infectionInfections and infestations | 94/1648 | 3/662 | 0/196 | 1/15 | 0/4197 |
Baseline analysis population included all participants who had been enrolled in THAOS study, signed the informed consent form, and either received doses of Tafamidis (presented by dose group) during the study or never received Tafamidis throughout the study.
| Age, Continuous(Years) | Tafamidis 20 mg Treated | Tafamidis 61/80 mg Treated-Overall | Tafamidis 20 mg to 61/80 mg Treated-Overall | Tafamidis Other Treated-Overall | Tafamidis Untreated | Total |
|---|---|---|---|---|---|---|
| Mean | 50.8 ± 17.75 | 76.0 ± 8.65 | 77.7 ± 10.66 | 77.9 ± 11.33 | 57.1 ± 19.08 | 58.1 ± 19.31 |
| Sex: Female, Male(Participants) | Tafamidis 20 mg Treated | Tafamidis 61/80 mg Treated-Overall | Tafamidis 20 mg to 61/80 mg Treated-Overall | Tafamidis Other Treated-Overall | Tafamidis Untreated | Total |
|---|---|---|---|---|---|---|
| Female | 734 | 62 | 33 | 4 | 1581 | 2414 |
| Male | 914 | 600 | 163 | 11 | 2616 | 4304 |
| Race/Ethnicity, Customized(Participants) | Tafamidis 20 mg Treated | Tafamidis 61/80 mg Treated-Overall | Tafamidis 20 mg to 61/80 mg Treated-Overall | Tafamidis Other Treated-Overall | Tafamidis Untreated | Total |
|---|---|---|---|---|---|---|
| Afro-Caribbean | 0 | 2 | 0 | 0 | 22 | 24 |
| American Hispanic | 8 | 4 | 0 | 1 | 16 | 29 |
| Asian | 110 | 12 | 3 | 0 | 170 | 295 |
| Black or African American | 11 | 53 | 3 | 2 | 225 | 294 |
| Caucasian | 600 | 512 | 46 | 12 | 2271 | 3441 |
| Latino American | 42 | 2 | 0 | 0 | 138 | 182 |
| Other | 18 | 0 | 1 | 0 | 113 | 132 |
| Missing | 859 | 77 | 143 | 0 | 1242 | 2321 |
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Plan to share: No — 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.
Ran from Jan 2008 to primary completion in Jun 2023, 185 months.
Results were first posted in Nov 2024, 1 year 5 months after primary completion.
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Amyloidosis, Hereditary, Transthyretin-Related →