Clinical Trial Details
— Status: Enrolling by invitation
Administrative data
| NCT number |
NCT06412432 |
| Other study ID # |
ERICA562023CRCA |
| Secondary ID |
|
| Status |
Enrolling by invitation |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
January 10, 2024 |
| Est. completion date |
June 30, 2026 |
Study information
| Verified date |
May 2024 |
| Source |
Federico II University |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
Notwithstanding the dramatic improvement associated with Tafamidis in Heart Failure (HF) due
to wild-type transthyretin cardiac amyloidosis (ATTRwt-CA), remarkable morbidity and
mortality still burden this disease. Exercise training (ET) is a first-line recommended
treatment for unselected HF patients, whose effects on ATTRwt-CA form remain however
unexplored. The investigators hereby present rationale and design of the Exercise training
and Rehabilitation in Cardiac Amyloidosis (ERICA) study, whose aim is to determine whether a
tailored, supervised ET program might improve exercise capacity in HF due to ATTRwt-CA. This
interventional, controlled study will randomize ATTRwt-CA patients into a control group (C)
and a primary training group (ET-1). After 12 weeks, patients in group C will be offered to
undergo the same ET program (ET-2) for further 12 weeks, considering the last observation as
baseline. Primary endpoint will be the distance obtained at the 6-minute walk test (6MWD)
performed at baseline and after 12-weeks of treatment in pooled ET-1 and ET-2 groups compared
to C. Quality of life, peak oxygen consumption, left and right heart architecture and
function, natriuretic peptides will be secondary endpoints. This study will be the first
testing the effects of ET in patients with ATTRwt-CA.
Description:
Among Systemic amyloidosis, the peculiar deposition of beta-amyloid fibrils agglomerates
localized in the interstitial space between the cardiomyocytes characterizes the spectrum of
cardiac amyloidosis (AC). All AC phenotypes culminate in a progressive deterioration of
cardiac compliance up to a true infiltrative cardiomyopathy with restrictive physiology.
Clinical presentation may vary from mildly symptomatic Heart Failure (HF), usually labeled,
and mistakenly confused as a classic Heart Failure with preserved ejection fraction (HFpEF)
up to a severe scenario of severe cardiac decompensation with fluid overload, marked
shortness of breath, fatigue and orthostatic hypotension. Syncope may also appear due to
infiltration in the conduction system leading to sinoatrial disease and atrioventricular
block. To date, more than 30 proteins responsible for the deposition of fibrils have been
identified and of these 9 have been identified as responsible for the cardiac involvement of
the disease. AC is determined in 98% of cases by the accumulation of monoclonal light chains
of immunoglobulins (AL) or transthyretin (ATTR); the latter can occur either in its
hereditary form (ATTRv) or in the wild-type variant (ATTRwt). Although AC is perceived as a
rare disease, standing a reported prevalence of around 1/100,000 inhabitants, a recent
metanalysis reported AC as underlying HF cause in 13.7% of cases, varying from 15.1% of Heart
Failure (HF) with preserved ejection fraction (HFpEF) and 11.3% in reduced fraction phenotype
(HFrEF). This mismatch begets the hypothesis that AC is often underdiagnosed, probably due to
its challenging diagnosis, the diverse spectrum of clinical presentation ranging from
severely compromised clinical cases to rather silent manifestations, and the absence of
specific therapies for this condition making until a few years ago AC a true orphan disease.
This paradigm has been subverted in recent years, by the emergence of tafamidis, a targeted
drug from amyloidosis that binds transthyretin, preventing tetramer dissociation and
production of amyloid. Tafamidis has been successfully tested for ATTRwt-AC in a relatively
large multicenter, international, double-blind, placebo-controlled, phase 3 trial, the
Transthyretin Amyloidosis Cardiomyopathy Clinical Trial (ATTR-ACT), showing a remarkable
improvement of the composite outcome of all-cause mortality and hospitalizations due to
cardiovascular causes. Apart from Tafamidis, there are no evidence supporting the use of
guideline-directed medical therapy (GDMT) used in classical forms of HF in ATTR-ACT. On top
of GDMT, exercise training (ET) remains largely uninvestigated in AC. ET consists of a
multidisciplinary approach, including a medical evaluation with modification of
cardiovascular risk factors, prescription of a physical exercise program and psychosocial
evaluation and is currently recommended with the highest degree of recommendation (in class
I, type A level) in current guidelines on HF. To date, there are no data about the efficacy
and safety of ET in AC, specifically in the ATTRwt-AC. We hereby present the outlines and the
study protocol of the Exercise Rehabilitation and training in Cardiac Amyloidosis (ERICA)
study, whose aim is to investigate and analyze the safety and the efficacy of cardiac
rehabilitation on patients with AC, specifically those affected by the ATTR-wt form. The
present study aims to investigate and analyze, through an interventional longitudinal,
controlled, randomized, design, the effects of a structured program of Exercise training in
patients with ATTRwt-AC.
