Effect of Trimetazidine on Coronary Flow in Transthyretin Cardiac Amyloidosis

NCT07836699 | Not Yet Recruiting Phase 2

• 1 other identifier: 94722525.6.0000.0068
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief 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. The main question this study aims to answer is: 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.

Conditions

Transthyretin Cardiac Amyloidosis

Keywords

Transthyretin Cardiac Amyloidosis; ATTR-CM; Trimetazidine; Coronary Flow Reserve; Coronary Microvascular Dysfunction; Myocardial Blood Flow; Myocardial Perfusion; Nitrogen-13 Ammonia PET/CT

Outcome Measures

Primary Outcomes (1)

• 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.

  Baseline to approximately 6 months

Secondary Outcomes (3)

• Change in 6-Minute Walk Distance

  Baseline to approximately 6 months

• Change in NT-proBNP

  Baseline to approximately 6 months

• Change in Kansas City Cardiomyopathy Questionnaire Score

  Baseline to approximately 6 months

Study Arms (1)

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.

Drug: Trimetazidine

Interventions

Trimetazidine DRUG

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.

Trimetazidine

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• Fábio Fernandes: lead

Study Sites (1)

Instituto do Coração (InCor), Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo

São Paulo, São Paulo, Brazil

Location

Related Publications (3)

• 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.

  PMID: 39033298 BACKGROUND

• Gao 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.

  PMID: 21134903 BACKGROUND

• Dorbala 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.

  PMID: 25023822 BACKGROUND

MeSH Terms

Interventions

Trimetazidine

Intervention Hierarchy (Ancestors)

Piperazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Central Study Contacts

Rafael Ruas Nastari, MD

CONTACT

+55 11 975111521; rafael_nastari@msn.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Collaborating Professor, Department of Cardiopneumology, University of São Paulo Medical School

Model Details: Single-arm, open-label pilot study in which all participants receive trimetazidine and are evaluated before and after approximately 6 months of treatment.

Study Record Dates

• First Submitted: September 17, 2026
• First Posted: September 23, 2026
• Study Start: September 1, 2026
• Primary Completion (Estimated): August 1, 2027
• Study Completion (Estimated): September 1, 2027
• Last Updated: September 23, 2026

Record last verified: 2026-09

Data Sharing

• IPD Sharing: Will not share

Locations

BR (1)