Enavogliflozin for the Management of Patients With Amyloid CardiomyopaThy

Official title

Enavogliflozin for the Management of Patients With Amyloid CardiomyopaThy - A Randomized, Double-Blind, Placebo-Controlled, Crossover, Multicenter Trial

Overview

This study aims to evaluate the safety and effectiveness of Enavogliflozin 0.3 mg, an SGLT2 inhibitor, in patients with amyloid cardiomyopathy. Participants will take both the study drug and a placebo in two separate periods, with a wash-out period in between. The goal is to determine whether Enavogliflozin is safe and effective for treating amyloid cardiomyopathy.

Detailed description

Patients with a confirmed diagnosis of cardiac amyloidosis and symptomatic heart failure (NYHA class II-III) will be recruited.

Participants will be randomized to receive either the study drug or placebo and will undergo baseline and 12-week assessments, including the Kansas City Cardiomyopathy Questionnaire (KCCQ), 6-minute walk test, and cardiopulmonary exercise testing. Following a 4-week washout period, participants will cross over to the alternate treatment arm (study drug or placebo) and repeat the same assessments at baseline and 12 weeks.

The primary endpoint will be the change in KCCQ Clinical Summary Score (KCCQ-CSS).

Interventions

• Drug Enavogliflozin 0.3mg
  Participants will receive Enavogliflozin 0.3 mg orally once daily for 12 weeks. The drug is administered in tablet form and is taken during the first or second treatment period of a crossover design.
• Drug Placebo
  Participants will receive placebo orally once daily for 12 weeks. The drug is administered in tablet form and is taken during the first or second treatment period of a crossover design.

Primary outcome measures

• Change in KCCQ-CSS from baseline to Week 12 [Time frame: Baseline and Week 12]

Secondary outcome measures (6)

• Change in 6-Minute Walk Distance [Time frame: Baseline and Week 12]
• Change in log-transformed NT-proBNP levels [Time frame: Baseline and Week 12]
• Change in Body Weight [Time frame: Baseline and Week 12]
• Change in Body Fat Percentage [Time frame: Baseline and Week 12]
• Change in Extracellular Water Ratio [Time frame: Baseline and Week 12]
• Incidence of Worsening Heart Failure Events or Death [Time frame: From baseline to Week 12 during each treatment period (excluding the 4-week washout period)]

Eligibility criteria

Inclusion criteria

• Adults aged 19 years or older
• Diagnosed with amyloid cardiomyopathy confirmed by cardiac biopsy or non-invasive imaging
• Presence of heart failure symptoms corresponding to NYHA functional class II-III
• Patients on stable oral diuretic use, without dose changes exceeding 50% of the previous dose, for at least 2 weeks prior to study enrollment
• Ambulatory (able to walk)
• Able to provide written informed consent for study participation

Exclusion criteria

• Pregnant or breastfeeding women
• Active infection
• Major cardiovascular events (e.g., myocardial infarction, stroke) within the past 6 months
• Scheduled for coronary revascularization, CRT-D implantation, atrial flutter/fibrillation ablation, or valve surgery
• History of heart transplantation
• Estimated glomerular filtration rate (eGFR) < 60 ml/min/1.73 m² (calculated by CKD-EPI formula)
• No history of cancer within the past 5 years at screening (except borderline cancers without recurrence for 2-3 years; multiple myeloma with cardiac involvement is classified as cardiac amyloidosis and is exempt)
• Heart failure primarily caused by severe left sided valvular disease or ischemic heart disease (except if valvular disease is corrected)
• Type 1 diabetes mellitus or insulin-dependent diabetes
• History of ketoacidosis, complicated urinary or genital infections, or kidney stones
• Systolic blood pressure < 80 mmHg or symptomatic hypotension
• Major surgery within 90 days prior to enrollment
• Known hypersensitivity or allergic reaction to the study drug or its components
• Moderate to severe liver impairment
• Chronic alcohol or substance abuse
• Residing in long-term care facilities (e.g., nursing homes)
• Unable to understand or comply with study drug, procedures, or follow-up, or who are deemed by the investigator to be unlikely to complete the study

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Crossover

Masking

Double blind

Primary purpose

Treatment

Study locations

South Korea · 2 centers

• Samsung Medical Center — Seoul
• Seoul St. Mary's Hospital, The Catholic University of Korea — Seoul

Publications

• Porcari A, Cappelli F, Nitsche C, Tomasoni D, Sinigiani G, Longhi S, Bordignon L, Masri A, Serenelli M, Urey M, Musumeci B, Cipriani A, Canepa M, Badr-Eslam R, Kronberger C, Chimenti C, Zampieri M, Allegro V, Razvi Y, Patel R, Ioannou A, Rauf MU, Petrie A, Whelan C, Emdin M, Metra M, Merlo M, Sinagra G, Hawkins PN, Solomon SD, Gillmore JD, Fontana M. SGLT2 Inhibitor Therapy in Patients With Transt PMID 38866445
• Packer M, Butler J, Zeller C, Pocock SJ, Brueckmann M, Ferreira JP, Filippatos G, Usman MS, Zannad F, Anker SD. Blinded Withdrawal of Long-Term Randomized Treatment With Empagliflozin or Placebo in Patients With Heart Failure. Circulation. 2023 Sep 26;148(13):1011-1022. doi: 10.1161/CIRCULATIONAHA.123.065748. Epub 2023 Aug 24. PMID 37621153

Identifiers

NCT: NCT07240844 · EMPACT · KC25MIDV0449

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗