Transthyretin (TTR) Amyloid CardiomyopathyPhase 3ATTR-ACTNCT01994889
Safety and Efficacy of Tafamidis in Patients With Transthyretin Cardiomyopathy
A Phase 3 study testing Tafamidis in people with Transthyretin (TTR) Amyloid Cardiomyopathy, run by Pfizer at 80 sites in 13 countries.
Trial summary
This Phase 3 study will investigate the efficacy, safety and tolerability of an oral daily dose of 20 mg or 80 mg tafamidis meglumine capsules compared to placebo in subjects with either transthyretin genetic variants or wild-type transthyretin resulting in amyloid cardiomyopathy. Read more about this study
- Who is it for?
- Ages 18 to 90 years
- Conditions the study is for
- Transthyretin (TTR) Amyloid Cardiomyopathy
- What is being tested?
- Tafamidis
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 441 participants
- Where
- 80 sitesin 13 countries
- Study dates
- 9 Dec 2013to 7 Feb 2018
- Phase
- Phase 3
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 90 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Medical history of Heart Failure (HF) with at least 1 prior hospitalization for HF or clinical evidence of HF (without hospitalization) manifested by signs or symptoms of volume overload or elevated intracardiac pressures (e.g., elevated jugular venous pressure, shortness of breath or signs of pulmonary congestion on x-ray or auscultation, peripheral edema) that required/requires treatment with a diuretic for improvement,
- Evidence of cardiac involvement by echocardiography with an end-diastolic interventricular septal wall thickness > 12 mm,
- Presence of amyloid deposits in biopsy tissue and presence of a variant TTR genotype and/or TTR precursor protein identification by immunohistochemistry, scintigraphy or mass spectrometry
Who cannot join
- A New York Heart Association (NYHA) classification of IV.
- Presence of primary (light chain) amyloidosis.
- Prior liver or heart transplantation or implanted cardiac mechanical assist device.
Trial locations and contacts
80 sites in 13 countries.
80 sites in 13 countries
United States50 sites
Michigan Medicine,University of Michigan
Ann Arbor, Michigan, 48109
University of Maryland, School of Medicine
Baltimore, Maryland, 21201
Johns Hopkins University
Baltimore, Maryland, 21287
The Johns Hopkins Hospital IDS Pharmacy
Baltimore, Maryland, 21287
The Kirklin Clinic
Birmingham, Alabama, 35249
UAB Hospital Department of Pharmacy IDS
Birmingham, Alabama, 35249
University Hospital, University of Alabama at Birmingham
Birmingham, Alabama, 35249
Boston Medical Center - Cardiovascular Center, Outpatient Clinic
Boston, Massachusetts, 02118
Boston Medical Center Investigational Pharmacy Services
Boston, Massachusetts, 02118
Boston Medical Center
Boston, Massachusetts, 02118
Boston University Medical Center General Clinical Research Unit
Boston, Massachusetts, 02118
Northwestern Medical Group
Chicago, Illinois, 60611
Northwestern Memorial Hospital
Chicago, Illinois, 60611
Cleveland Clinic
Cleveland, Ohio, 44195
UM Sylvester at Deerfield Beach
Deerfield Beach, Florida, 33442
Duke University Health System
Durham, North Carolina, 27710
Houston Methodist Hospital
Houston, Texas, 77030
UCSD Clinical and Translational Research Institute, Investigational Drug Service
La Jolla, California, 92037-0620
Altman Clinical Translational Research institute
La Jolla, California, 92037-0990
Altman Clinical Translational Research Institute
La Jolla, California, 92037
UCSD Sulpizio Cardiovascular Center
La Jolla, California, 92037
Cedars-Sinai Medical Center, Investigational Drug Pharmacy Services
Los Angeles, California, 90048
Cedars-Sinai Medical Center
Los Angeles, California, 90048
Cedars-Sinai Medical Care Foundation
Los Angeles, California, 90211
University of Miami Hospital & Clinics
Miami, Florida, 33136
Vanderbilt University Medical Center
Nashville, Tennessee, 37232
Ochsner Medical Center
New Orleans, Louisiana, 70121
New York University Hospitals
New York, New York, 10016
Icahn School of Medicine at Mount Sinai and Mount Sinai Hospital
New York, New York, 10029
Mount Sinai Doctors Faculty Practice
New York, New York, 10029
The Mount Sinai Hospital Department of Pharmacy
New York, New York, 10029
Columbia University Medical Center Research Pharmacy
New York, New York, 10032
Columbia University Medical Center/Clinical Cardiovascular Research Laboratory for the Elderly
New York, New York, 10034
Newark Beth Israel Medical Center
Newark, New Jersey, 07112
Advocate Christ Medical Centre
Oak Lawn, Illinois, 60453
Penn Presbyterian Medical Center
Philadelphia, Pennsylvania, 19104
Mayo Clinic Arizona - Mayo Clinic Speciality Building
Phoenix, Arizona, 85054
Mayo Clinic Hospital
Phoenix, Arizona, 85054
OHSU Center for Health and Healing
Portland, Oregon, 97239
OHSU Research Pharmacy Services
Portland, Oregon, 97239
Oregon Health and Science University (OHSU)
Portland, Oregon, 97239
VCU Medical Center - Ambulatory Care Clinic
Richmond, Virginia, 23298
VCU Medical Center - Main Hospital
Richmond, Virginia, 23298
Mayo Clinic Pharmacy Research Supp
Rochester, Minnesota, 55905
Mayo Clinic
Rochester, Minnesota, 55905
University of Utah,Health Sciences Center
Salt Lake City, Utah, 84132
UCSF Cardiovascular Care and Prevention Center
San Francisco, California, 94143
Mayo Clinic Arizona - Mayo Clinic Building
Scottsdale, Arizona, 85259
Virginia Mason Medical Center
Seattle, Washington, 98101
Stanford University Hospital and Clinics
Stanford, California, 94305
Czechia6 sites
Fakultni nemocnice u sv. Anny, Nemocnicni lekarna
Brno, 656 91
Nemocnice u sv. Anny v Brne
Brno, 656 91
Vseobecna fakultni nemocnice v Praze
Prague, 128 08
Vseobecna fakultni nemocnice v Praze, Nemocnicni lekarna
Prague, 12808
IKEM, Ustavni lekarna
Prague, 140 21
IKEM
Prague, 140 21
Italy4 sites
U.O. Cardiologia- Prof. Rapezzi
Bologna, 40138
Unita Operativa di Cardiologia
Brescia, 25123
S.O.D. Cardiologia Generale 1 - D.A.I. del Cuore e dei Vasi
Florence, 50134
Centro per lo Studio e la Cura Delle Amiloidosi Sistemiche - Fondazione IRCCS Policlinico S. Matteo
Pavia, 27100
Japan3 sites
Kumamoto University Hospital
Kumamoto, Kumamoto, 8608556
Kurume University Hospital
Kurume-shi, Fukuoka, 830-0011
Shinshu University Hospital
Nagano, 390-8621
Spain3 sites
Hospital Universitario A Coruna
A Coruña, 15006
Hospital Clinico Universitario Virgen de la Arrixaca
El Palmar, Murcia, 30120
Hospital Universitario Puerta De Hierro - Majadahonda
Majadahonda, Madrid, 28222
United Kingdom3 sites
St Bartholomew's Hospital-Barts Health NHS Trust
London, EC1A 7BE
St. George's Hospital (St George's Healthcare NHS Trust)
London, SW17 0QT
St. George's University of London
London, SW17 0RE
Canada2 sites
University of Calgary/Foothills Medical Centre
Calgary, Alberta, T2N 4Z6
Toronto General Hospital
Toronto, Ontario, M5G 2N2
France2 sites
Hopital Antoine Beclere
Clamart, 92140
CHU Henri Mondor
Créteil, 94010
Germany2 sites
Medical University of Heidelberg
Heidelberg, 69120
Universitaetsklinikum Muenster
Münster, 48149
Sweden2 sites
Medicin-Geriatrik kliniken-Skelleftea lasarett
Skellefteå, 93186
Sjukhusvägen, Akademiska sjukhuset
Uppsala, 751 85
Brazil1 site
Unidade de Pesquisa Clinica / Hospital Universitario Clementino Fraga Filho / UFRJ
Rio de Janeiro, Rio de Janeiro, 21941-913
About this study
Official title: A MULTICENTER, INTERNATIONAL, PHASE 3, DOUBLE-BLIND, PLACEBO-CONTROLLED, RANDOMIZED STUDY TO EVALUATE THE EFFICACY, SAFETY, AND TOLERABILITY OF DAILY ORAL DOSING OF TAFAMIDIS MEGLUMINE (PF-06291826) 20 MG OR 80 MG IN COMPARISON TO PLACEBO IN SUBJECTS DIAGNOSED WITH TRANSTHYRETIN CARDIOMYOPATHY (TTR-CM)
This Phase 3 study will investigate the efficacy, safety and tolerability of an oral daily dose of 20 mg or 80 mg tafamidis meglumine capsules compared to placebo in subjects with either transthyretin genetic variants or wild-type transthyretin resulting in amyloid cardiomyopathy.
Read the detailed description
Phase 3, multicenter, global, three-arm, parallel design, placebo-controlled, double-blind, randomized study to determine efficacy, safety and tolerability of tafamidis on clinical outcomes (all-cause mortality and frequency of cardiovascular-related hospitalizations) in subjects with either transthyretin genetic variants or wild-type transthyretin resulting in amyloid cardiomyopathy.
- Being tested
- Tafamidis, Placebo
- Keywords
- amyloidosis, amyloid, transthyretin, TTR
- Medical subject headings
- Amyloid Neuropathies, Familial, Amyloidosis, Alzheimer Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TafamidisDrug
Tafamidis 20 mg in soft gel capsules administered once a day for 30 months
TafamidisDrug
Tafamidis 80 mg in soft gel capsules administered once a day for 30 months
PlaceboDrug
Placebo in soft gel capsules administered once a day for 30 months
| Study group | Role | What they receive |
|---|---|---|
| Tafamidis - 20 mg | Experimental | Active Treatment-Low dose Receives: Drug: Tafamidis |
| Tafamidis - 80 mg | Experimental | Active Treatment-High Dose Receives: Drug: Tafamidis |
| Placebo | Placebo comparator | Placebo control Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Hierarchical Combination of All-Cause Mortality and Frequency of Cardiovascular-Related Hospitalizations
All-cause mortality and frequency of cardiovascular hospitalization were analyzed using Finkelstein-Schoenfeld method. The method combines all-cause mortality and frequency of CV-related hospitalizations in a hierarchical fashion using all-cause mortality first. The method compares every participant with every other participant within strata, assigning a +1 to the "better" participant and a -1 to the "worse" participant and 0 if they are "tied". Participants who discontinued for transplantation (heart transplantation and combined heart and liver transplantation) or for implantation of a cardiac mechanical assist device, were handled in the same manner as death. 'Win' represents a participant doing better based on hierarchical comparison. The reported unit is the total "wins" for each treatment group from performing such a hierarchical comparison across all 4 strata in the study.
Measured: Baseline up to Month 30
Secondary outcomes (6)
All-Cause Mortality
Number of deaths due to any cause was analyzed. Participants who discontinued for transplantation (heart transplantation and combined heart and liver transplantation) or for implantation of a cardiac mechanical assist device were handled in the same manner as death.
Measured: Baseline up to Month 30
Frequency of Cardiovascular-Related Hospitalizations
CV related hospitalizations per year is calculated as participant's number of CV related hospitalizations upon duration on study in years.
Measured: Baseline to Month 30
Change From Baseline in the Total Distance Walked During 6 Minute Walk Test (6MWT) at Month 30
6MWT is the total distance that a participant could walk in 6 minutes. Participants were asked to perform the test at a pace that was comfortable to them, with as many breaks as they needed.
Measured: Baseline, Month 30
Change From Baseline in Kansas City Cardiomyopathy Questionnaire Overall Score (KCCQ-OS) at Month 30
KCCQ is a 23-item participant-completed questionnaire that assesses health status and health-related quality of life in participants with heart failure. Eight domain scores were calculated for the KCCQ: Physical limitation, Social limitation, Quality of life, Self-efficacy, Symptom stability, Symptom frequency, Symptom burden, and Total symptoms (calculated as the mean of Symptom frequency and Symptom burden scores). Two summary scores were also calculated: Clinical Summary (calculated as mean of Physical limitation and Total symptom scores) and Overall Summary (calculated as mean of Physical limitation, Social limitation, Total symptoms, and Quality of life scores). Domain and summary scores were scaled to range from 0 (minimum) to 100 (maximum); higher scores represent better health status.
Measured: Baseline, Month 30
Number of Participants With Cardiovascular-Related Mortality
Deaths adjudicated as CV-related and indeterminate are reported. Participants who discontinued for transplantation (heart transplantation and combined heart and liver transplantation) or for implantation of a cardiac mechanical assist device, were handled in the same manner as death.
Measured: Baseline up to Month 30
Percentage of Participants With Stabilized Transthyretin (TTR) at Month 1
TTR stabilization is a measure of the degree of stabilization afforded the TTR molecule by tafamidis.
Measured: Month 1
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Nov 2013 (estimated)
- Study start9 Dec 2013
- Primary completion7 Feb 2018
- Study completion7 Feb 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (30)Papers the sponsor has linked to this study.
- Other trials for Transthyretin (TTR) Amyloid CardiomyopathyStudies of the same condition, open and under way.
- More trials run by PfizerThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 441 participants (actual)
Sponsor and investigators
- Lead sponsor
- Pfizer
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Pfizer CT.gov Call Center, Study director, Pfizer
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01994889
- Sponsor's protocol ID
- B3461028
- Other IDs
- 2012-002465-35, ATTR-ACT
- Acronym
- ATTR-ACT
- Status last verified
- Apr 2019
- First submitted
- 14 Nov 2013
- Last updated
- 24 Apr 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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.
Publications
Damy T, Witteles R, Cappelli F, Wang R, Grogan M. Cardiovascular-Related Mortality and Hospitalizations in Patients with Transthyretin Amyloid Cardiomyopathy Treated with Tafamidis: A Post Hoc Analysis of the Phase 3 ATTR-ACT and Long-Term Extension. Cardiol Ther. 2026 Aug 27. doi: 10.1007/s40119-026-00470-8. Online ahead of print.
PubMed 42658466Maurer MS, Elliott P, Kelly JW, Hanna M, Powers ET, Riley S, Wang R, Garcia-Pavia P. Impact of Tafamidis on Transthyretin Concentration and Its Relation to All-Cause Mortality in Patients with Transthyretin Amyloid Cardiomyopathy: An Analysis from ATTR-ACT. Cardiol Ther. 2026 Aug 27. doi: 10.1007/s40119-026-00468-2. Online ahead of print.
PubMed 42658464Witteles R, Hanna MA, Grogan M, Elliott P, Wang R, Garcia-Pavia P. Functional Stability Measured by Changes in the 6-min Walk Test in Patients Treated with Tafamidis Versus Placebo: Post hoc Analysis from ATTR-ACT. Cardiol Ther. 2026 Aug 27. doi: 10.1007/s40119-026-00471-7. Online ahead of print.
PubMed 42658463Damy T, Wang R, Maurer MS, Gillmore JD, Fontana M. Long-term efficacy of tafamidis in patients with transthyretin amyloid cardiomyopathy by National Amyloidosis Centre stage. Eur J Heart Fail. 2025 Dec;27(12):2998-3009. doi: 10.1002/ejhf.3696. Epub 2025 Jun 9.
PubMed 40488446Grogan M, Davis MK, Crespo Leiro MG, Sultan MB, Gundapaneni B, Angeli FS, Hanna M. The effect of long-term tafamidis treatment on quality of life in people with transthyretin amyloid cardiomyopathy (ATTR-CM): A plain language summary. Future Cardiol. 2024;20(11-12):595-603. doi: 10.1080/14796678.2024.2391250. Epub 2024 Sep 11.
PubMed 39258729Witteles R, Jefferies JL, Kapa S, Cappelli F, Sultan MB, Gundapaneni B, Davis MK, Garcia-Pavia P. Atrial Fibrillation as a Prognostic Factor for All-Cause Mortality in Patients With Transthyretin Amyloid Cardiomyopathy. JACC CardioOncol. 2024 Apr 30;6(4):592-598. doi: 10.1016/j.jaccao.2024.03.007. eCollection 2024 Aug.
PubMed 39239341Hanna M, Fine NM, Gundapaneni B, Sultan MB, Witteles RM. Improvements in Efficacy Measures With Tafamidis in the Tafamidis in Transthyretin Cardiomyopathy Clinical Trial. JACC Adv. 2022 Dec 14;1(5):100148. doi: 10.1016/j.jacadv.2022.100148. eCollection 2022 Dec.
PubMed 38939456Drachman B, Damy T, Hanna M, Wang R, Angeli FS, Garcia-Pavia P. Long-term tafamidis efficacy in patients with transthyretin amyloid cardiomyopathy by baseline left ventricular ejection fraction. Eur J Heart Fail. 2024 Sep;26(9):2038-2046. doi: 10.1002/ejhf.3330. Epub 2024 Jun 26.
PubMed 38932583Sperry BW, Sultan MB, Gundapaneni B, Tai SS, Witteles RM. Effect of Tafamidis on Renal Function in Patients With Transthyretin Amyloid Cardiomyopathy in ATTR-ACT. JACC CardioOncol. 2024 Apr 16;6(2):300-306. doi: 10.1016/j.jaccao.2024.02.007. eCollection 2024 Apr.
PubMed 38774010Shah SJ, Fine N, Garcia-Pavia P, Klein AL, Fernandes F, Weissman NJ, Maurer MS, Boman K, Gundapaneni B, Sultan MB, Elliott P. Effect of Tafamidis on Cardiac Function in Patients With Transthyretin Amyloid Cardiomyopathy: A Post Hoc Analysis of the ATTR-ACT Randomized Clinical Trial. JAMA Cardiol. 2024 Jan 1;9(1):25-34. doi: 10.1001/jamacardio.2023.4147.
PubMed 37966817Garcia-Pavia P, Sultan MB, Gundapaneni B, Sekijima Y, Perfetto F, Hanna M, Witteles R. Tafamidis Efficacy Among Octogenarian Patients in the Phase 3 ATTR-ACT and Ongoing Long-Term Extension Study. JACC Heart Fail. 2024 Jan;12(1):150-160. doi: 10.1016/j.jchf.2023.08.032. Epub 2023 Nov 8.
PubMed 37943223Elliott P, Gundapaneni B, Sultan MB, Ines M, Garcia-Pavia P. Improved long-term survival with tafamidis treatment in patients with transthyretin amyloid cardiomyopathy and severe heart failure symptoms. Eur J Heart Fail. 2023 Nov;25(11):2060-2064. doi: 10.1002/ejhf.2974. Epub 2023 Jul 26.
PubMed 37434378Bhambri R, Colavecchia AC, Bruno M, Chen Y, Alvir J, Roy A, Kemner J, Crowley A, Benjumea D, Gilstrap L. Real-World Characteristics of Patients with Wild-Type Transthyretin Amyloid Cardiomyopathy: An Analysis of Electronic Healthcare Records in the United States. Am J Cardiovasc Drugs. 2023 Mar;23(2):197-206. doi: 10.1007/s40256-022-00563-4. Epub 2023 Feb 13.
PubMed 36780092Sperry BW, Hanna M, Maurer MS, Nativi-Nicolau J, Floden L, Stewart M, Wyrwich KW, Barsdorf AI, Kapadia H, Spertus JA. Association of Tafamidis With Health Status in Patients With ATTR Cardiac Amyloidosis: A Post Hoc Analysis of the ATTR-ACT Randomized Clinical Trial. JAMA Cardiol. 2023 Mar 1;8(3):275-280. doi: 10.1001/jamacardio.2022.5251.
PubMed 36723935Elliott P, Drachman BM, Gottlieb SS, Hoffman JE, Hummel SL, Lenihan DJ, Ebede B, Gundapaneni B, Li B, Sultan MB, Shah SJ. Long-term survival in people with transthyretin amyloid cardiomyopathy who took tafamidis: A Plain Language Summary. Future Cardiol. 2023 Jan;19(1):7-17. doi: 10.2217/fca-2022-0096. Epub 2023 Jan 30.
PubMed 36715498