Transthyretin Cardiac AmyloidosisPhase 2TACT-TTRNCT07836699
Effect of Trimetazidine on Coronary Flow in Transthyretin Cardiac Amyloidosis
A Phase 2 study testing Trimetazidine in people with Transthyretin Cardiac Amyloidosis, run by Fábio Fernandes at 1 site in Brazil.
Trial summary
The goal of this clinical trial is to learn if trimetazidine can improve blood flow in the heart in adults with transthyretin cardiac amyloidosis (ATTR-CM). ATTR-CM is a condition in which an abnormal protein builds up in the heart and can make it harder for the heart to work normally. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Transthyretin Cardiac Amyloidosis
- What is being tested?
- Trimetazidine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteBrazil
- Study dates
- Jan 2027to 1 Sep 2027
- Phase
- Phase 2
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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Diagnosis of transthyretin cardiac amyloidosis confirmed by all protocol-specified diagnostic criteria or by Congo red-positive tissue biopsy with cardiac involvement. The diagnostic criteria listed in the current protocol include:
- Interventricular septal thickness >12 mm on echocardiography or cardiac magnetic resonance imaging, in the absence of other causes of hypertrophy (e.g., hypertension or aortic stenosis)
- History of signs or symptoms of heart failure consistent with cardiac amyloidosis
- Cardiac scintigraphy with technetium-99m pyrophosphate showing grade II or III uptake according to the Perugini scale
- Age >18 years
- New York Heart Association (NYHA) functional class II, III, or IV
Who cannot join
- Previous adverse reaction, intolerance, or other contraindication to trimetazidine
- Serum kappa/lambda ratio outside the normal range
- Use of calcium channel blockers, beta-blockers, or nitrates
- Obstructive coronary artery disease, defined as >50% stenosis in any major epicardial coronary artery, demonstrated by coronary computed tomography angiography
- Active infection, inflammatory disease, or other systemic condition that may affect myocardial perfusion
- Contraindication to dipyridamole or PET/CT imaging
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- Estimated glomerular filtration rate <30 mL/min/1.73 m², calculated using the CKD-EPI equation
- Pregnancy or postpartum period
- Presence of diseases other than cardiac amyloidosis that may impair functional capacity or limit ambulation during the 6-minute walk test
- Other medical conditions or comorbidities that, in the investigator's opinion, may interfere with the course of the study or interpretation of the data
- Refusal to provide written informed consent
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Brazil1 site
Instituto do Coração (InCor), Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo
São Paulo, São Paulo
Rafael Ruas Nastari, MD, +55 11 975111521, rafael_nastari@msn.com
About this study
Official title: Evaluation of the Effect of Trimetazidine on Coronary Flow in Transthyretin Cardiac Amyloidosis
The goal of this clinical trial is to learn if trimetazidine can improve blood flow in the heart in adults with transthyretin cardiac amyloidosis (ATTR-CM). ATTR-CM is a condition in which an abnormal protein builds up in the heart and can make it harder for the heart to work normally.
The main question this study aims to answer is:
Read more
Does trimetazidine improve the heart's ability to increase its blood flow when more blood is needed?
The study will also look at whether treatment is linked to changes in walking ability, heart-related blood tests, heart function, and quality of life.
Participants will:
Take trimetazidine for about 6 months. Have heart blood flow measured with a positron emission tomography/computed tomography (PET/CT) scan before and after treatment.
Have heart ultrasound examinations and blood tests. Complete a 6-minute walk test and a questionnaire about their symptoms and quality of life.
Read the detailed description
Transthyretin cardiac amyloidosis (ATTR-CM) is characterized by the deposition of transthyretin amyloid fibrils within the myocardium. In addition to myocardial infiltration, amyloid deposition may involve intramyocardial vessels and contribute to coronary microvascular dysfunction. This may lead to impaired myocardial perfusion and reduced coronary flow reserve even in the absence of significant obstructive epicardial coronary artery disease.
Trimetazidine is a metabolic modulator that shifts myocardial energy metabolism from fatty acid oxidation toward glucose oxidation. This metabolic effect may improve myocardial energy efficiency and reduce oxygen requirements for adenosine triphosphate production. These properties provide the rationale for investigating whether trimetazidine may improve coronary microvascular function in people with ATTR-CM.
TACT-TTR is a prospective, open-label, single-center, single-arm pilot clinical trial conducted at the Instituto do Coração, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (InCor-HCFMUSP). The study will enroll 20 participants with ATTR-CM who will receive trimetazidine and undergo approximately 6 months of follow-up.
Coronary physiology will be assessed using quantitative myocardial perfusion imaging with nitrogen-13 ammonia positron emission tomography/computed tomography (PET/CT). Myocardial blood flow will be measured at rest and during pharmacologic stress, allowing calculation of coronary flow reserve as the ratio of stress myocardial blood flow to resting myocardial blood flow. Participants will undergo assessments before and after the treatment period to investigate changes in coronary microvascular function. Additional clinical, imaging, laboratory, functional, and health-related quality-of-life assessments will be performed during follow-up.
This exploratory pilot study is intended to provide preliminary evidence on the potential role of trimetazidine as an adjunctive metabolic therapy targeting coronary microvascular dysfunction in ATTR-CM and to generate data that may support the design of future controlled clinical trials.
- Conditions
- Transthyretin Cardiac Amyloidosis
- Being tested
- Trimetazidine
- Keywords
- Transthyretin Cardiac Amyloidosis, ATTR-CM, Trimetazidine, Coronary Flow Reserve, Coronary Microvascular Dysfunction, Myocardial Blood Flow, Myocardial Perfusion, Nitrogen-13 Ammonia PET/CT
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TrimetazidineDrug
Participants will receive trimetazidine 35 mg orally twice daily for 6 months. Participants with an estimated glomerular filtration rate between 30 and 60 mL/min/1.73 m² will receive 35 mg orally once daily.
| Study group | Role | What they receive |
|---|---|---|
| Trimetazidine | Experimental | Trimetazidine 35 mg twice daily for 6 months. Participants with an estimated glomerular filtration rate between 30 and 60 mL/min/1.73 m² will receive 35 mg once daily. Receives: Drug: Trimetazidine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Coronary Flow Reserve
Coronary flow reserve (CFR) will be measured using nitrogen-13 ammonia PET/CT. CFR is calculated as the ratio of myocardial blood flow during pharmacologic stress to myocardial blood flow at rest. The outcome will assess the change in CFR from baseline to the end of trimetazidine treatment.
Measured: Baseline to approximately 6 months
Secondary outcomes (3)
Change in 6-Minute Walk Distance
Health-related quality of life will be assessed using the Kansas City Cardiomyopathy Questionnaire (KCCQ). Scores range from 0 to 100, with higher scores indicating better health status and fewer heart failure-related symptoms and limitations. The change in KCCQ score from baseline to approximately 6 months will be assessed.
Measured: Baseline to approximately 6 months
Change in NT-proBNP
Change in N-terminal pro-B-type natriuretic peptide (NT-proBNP) concentration from baseline to approximately 6 months. The study will assess whether NT-proBNP decreases by 30% or more from baseline.
Measured: Baseline to approximately 6 months
Change in Kansas City Cardiomyopathy Questionnaire Score
Health-related quality of life will be assessed using the Kansas City Cardiomyopathy Questionnaire (KCCQ). Scores range from 0 to 100, with higher scores indicating better health status and fewer heart failure-related symptoms and limitations. The change in KCCQ score from baseline to approximately 6 months will be assessed.
Measured: Baseline to approximately 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Sep 2026
- Study startJan 2027 (estimated)
- Primary completion1 Aug 2027 (estimated)
- Study completion1 Sep 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Transthyretin Cardiac AmyloidosisStudies of the same condition, open and under way.
- 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Single-arm, open-label pilot study in which all participants receive trimetazidine and are evaluated before and after approximately 6 months of treatment.
- Masking
- None (open label)
- Enrolment
- 20 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Fábio Fernandes
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Fábio Fernandes, University of Sao Paulo General Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07836699
- Sponsor's protocol ID
- 94722525.6.0000.0068
- Acronym
- TACT-TTR
- Status last verified
- Oct 2026
- First submitted
- 17 Sep 2026
- Last updated
- 23 Oct 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: Individual participant data (IPD) are not planned to be shared because the current study protocol does not include a formal plan for sharing de-identified participant-level data with external researchers. Study results will be disseminated through scientific presentations and publication.
Publications
Fernandes F, Luzuriaga GDCJ, da Fonseca GWP, Correia EB, Carvalho AAS, Macedo AVS, Coelho-Filho OR, Scheinberg P, Antunes MO, Schwartzmann PV, Mangini S, Marques W, Simoes MV. Clinical and genetic profiles of patients with hereditary and wild-type transthyretin amyloidosis: the Transthyretin Cardiac Amyloidosis Registry in the state of Sao Paulo, Brazil (REACT-SP). Orphanet J Rare Dis. 2024 Jul 20;19(1):273. doi: 10.1186/s13023-024-03281-z.
PubMed 39033298Gao D, Ning N, Niu X, Hao G, Meng Z. Trimetazidine: a meta-analysis of randomised controlled trials in heart failure. Heart. 2011 Feb;97(4):278-86. doi: 10.1136/hrt.2010.208751. Epub 2010 Dec 5.
PubMed 21134903Dorbala S, Vangala D, Bruyere J Jr, Quarta C, Kruger J, Padera R, Foster C, Hanley M, Di Carli MF, Falk R. Coronary microvascular dysfunction is related to abnormalities in myocardial structure and function in cardiac amyloidosis. JACC Heart Fail. 2014 Aug;2(4):358-67. doi: 10.1016/j.jchf.2014.03.009. Epub 2014 Jul 9.
PubMed 25023822