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Trial record 1 of 1 for:    NCT01994889
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Safety and Efficacy of Tafamidis in Patients With Transthyretin Cardiomyopathy (ATTR-ACT)

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ClinicalTrials.gov Identifier: NCT01994889
Recruitment Status : Completed
First Posted : November 26, 2013
Results First Posted : April 3, 2019
Last Update Posted : April 24, 2019
Sponsor:
Information provided by (Responsible Party):
Pfizer

Tracking Information
First Submitted Date  ICMJE November 14, 2013
First Posted Date  ICMJE November 26, 2013
Results First Submitted Date  ICMJE January 31, 2019
Results First Posted Date  ICMJE April 3, 2019
Last Update Posted Date April 24, 2019
Actual Study Start Date  ICMJE December 9, 2013
Actual Primary Completion Date February 7, 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 14, 2019)
Hierarchical Combination of All-Cause Mortality and Frequency of Cardiovascular-Related Hospitalizations [ Time Frame: Baseline up to Month 30 ]
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.
Original Primary Outcome Measures  ICMJE
 (submitted: November 20, 2013)
All-cause mortality and frequency of cardiovascular-related hospitalization [ Time Frame: From Baseline to Month 30 ]
A hierarchical combination of the endpoints for a pooled analysis of the tafamidis treatment groups in comparison to placebo
Change History Complete list of historical versions of study NCT01994889 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: March 14, 2019)
  • All-Cause Mortality [ Time Frame: Baseline up to Month 30 ]
    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.
  • Frequency of Cardiovascular-Related Hospitalizations [ Time Frame: Baseline to Month 30 ]
    CV related hospitalizations per year is calculated as participant's number of CV related hospitalizations upon duration on study in years.
  • Change From Baseline in the Total Distance Walked During 6 Minute Walk Test (6MWT) at Month 30 [ Time Frame: Baseline, 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.
  • Change From Baseline in Kansas City Cardiomyopathy Questionnaire Overall Score (KCCQ-OS) at Month 30 [ Time Frame: Baseline, 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.
  • Number of Participants With Cardiovascular-Related Mortality [ Time Frame: Baseline up to Month 30 ]
    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.
  • Percentage of Participants With Stabilized Transthyretin (TTR) at Month 1 [ Time Frame: Month 1 ]
    TTR stabilization is a measure of the degree of stabilization afforded the TTR molecule by tafamidis.
Original Secondary Outcome Measures  ICMJE
 (submitted: November 20, 2013)
  • 6-Minute Walk Test (6MWT). [ Time Frame: From Baseline to Month 30 ]
    Change from Baseline to Month 30 in the total distance walked in 6 minutes.
  • Kansas City Cardiomyopathy Questionnaire (KCCQ) [ Time Frame: From Baseline to Month 30 ]
    Change from Baseline to Month 30 in the Kansas City Cardiomyopathy Questionnaire Overall Score (KCCQ-OS).
  • Cardiovascular-related mortality [ Time Frame: From Baseline to Month 30 ]
    The total number of deaths adjudicated as being related to cardiovascular causes.
  • Frequency of Cardiovascular-Related Hospitalizations [ Time Frame: From Baseline to Month 30 ]
    The number of times that a subject is hospitalized for cardiovascular-related causes.
  • All-cause mortality [ Time Frame: From Baseline to Month 30 ]
    The total number of deaths in the study.
  • TTR stabilization at Month 1 [ Time Frame: From Baseline to Month 1 ]
    Tafamidis stabilizes the transthyretin (TTR) tetramer by binding with very high affinity to the two thyroxine binding sites, preventing the tetramer from dissociating along the weak dimer-dimer interface. TTR stabilization is a measure of the degree of stabilization afforded the TTR molecule by tafamidis, expressed as a percentage change from baseline.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Safety and Efficacy of Tafamidis in Patients With Transthyretin Cardiomyopathy
Official Title  ICMJE 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)
Brief 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.
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Transthyretin (TTR) Amyloid Cardiomyopathy
Intervention  ICMJE
  • Drug: Tafamidis
    Tafamidis 20 mg in soft gel capsules administered once a day for 30 months
  • Drug: Tafamidis
    Tafamidis 80 mg in soft gel capsules administered once a day for 30 months
  • Drug: Placebo
    Placebo in soft gel capsules administered once a day for 30 months
Study Arms  ICMJE
  • Experimental: Tafamidis - 20 mg
    Active Treatment-Low dose
    Intervention: Drug: Tafamidis
  • Experimental: Tafamidis - 80 mg
    Active Treatment-High Dose
    Intervention: Drug: Tafamidis
  • Placebo Comparator: Placebo
    Placebo control
    Intervention: Drug: Placebo
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: April 2, 2018)
441
Original Estimated Enrollment  ICMJE
 (submitted: November 20, 2013)
400
Actual Study Completion Date  ICMJE February 7, 2018
Actual Primary Completion Date February 7, 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 90 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Belgium,   Brazil,   Canada,   Czechia,   France,   Germany,   Italy,   Japan,   Netherlands,   Spain,   Sweden,   United Kingdom,   United States
Removed Location Countries Czech Republic
 
Administrative Information
NCT Number  ICMJE NCT01994889
Other Study ID Numbers  ICMJE B3461028
2012-002465-35 ( EudraCT Number )
ATTR-ACT ( Other Identifier: Alias Study Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.
URL: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests
Responsible Party Pfizer
Study Sponsor  ICMJE Pfizer
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Pfizer CT.gov Call Center Pfizer
PRS Account Pfizer
Verification Date April 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP