Sacubitril/valsartan in the prevention of disease progression in patients with an ancient arrhythmogenic service - ARNI-ARVC multicentre randomized trial

2024-517412-29-00 Protocol 2021/ABM/01/00004 Therapeutic confirmatory (Phase III) Ongoing, recruiting

Start 10 Jul 2023 · Status Ongoing, recruiting · 1 EU/EEA countries · 8 sites · Protocol 2021/ABM/01/00004

Overview

Sponsor-declared trial summary

Phase Therapeutic confirmatory (Phase III)
Status Ongoing, recruiting
Participants planned 120
Countries 1
Sites 8

arrhythmogenic in the old space of cardiomyopathy

The aim of the ARNI-ARVC study is to assess the anti-fibrotic and antiremodeling effects of sacubitril / valsartan in ARVC.

Key facts

Sponsor
Narodowy Instytut Kardiologii Stefana Kardynala Wyszynskiego Panstwowy Instytut Badawczy
Participant type
Patients
Age range
18-64 years, 65+ years
Gender
Male and Female
Therapeutic area
Diseases [C] - Cardiovascular Diseases [C14]
Trial duration
10 Jul 2023 → ongoing
Decision date (initial)
2024-10-31
Transition trial
Yes
Low-intervention
No
Rare-disease indication
Yes
Vulnerable population
No
Funding sources
Medical Research Agency

External identifiers

EU CT number
2024-517412-29-00
EudraCT number
2022-000457-89

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety, Therapy

The aim of the ARNI-ARVC study is to assess the anti-fibrotic and antiremodeling effects of sacubitril / valsartan in ARVC.

Conditions and MedDRA coding

arrhythmogenic in the old space of cardiomyopathy

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 4

  1. certain diagnosis of ARVC based on the 2010 International Task Force Criteria (ITFC) diagnostic criteria
  2. age> 18 years
  3. expressing a written informed consent to participate in the project
  4. Left ventricular ejection fraction (LVEF) ≥ 40% as assessed by CMR.

Exclusion criteria 3

  1. contraindications for CMR: - claustrophobia - cochlear implant - ferromagnetic material in tissues
  2. symptoms of end-stage right ventricular failure (dyspnoea, massive peripheral edema, enlargement of the liver and abdominal circumference, positive jugular vein pulsation)
  3. contraindications to the use of sacubitril / valsartan: - drug intolerance History of angioedema related to prior treatment with an angiotensin converting enzyme inhibitor or an angiotensin II receptor antagonist - hereditary or idiopathic angioedema - hyperkalaemia greater than 5.4 mmol / l - severe hepatic impairment - biliary cirrhosis and cholestasis - Child-Pugh grade C - renal failure with eGFR <30 ml / min / 1.73 m2 - hypersensitivity to the active substances or any of the excipients - taking direct renin inhibitors - pregnancy - lactation.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 3

  1. the degree of fibrosis of the left ventricular muscle in the CMR examination
  2. left ventricular ejection fraction (LVEF) in CMR
  3. ventricular arrhythmias load

Secondary endpoints 7

  1. NT-proBNP concentration and two fibrosis markers: sST2 and Gal-3
  2. morphological and functional criteria (ECHO and CMR): the size of the left and right ventricles as well as generalized and focal contractility disorders
  3. ECG: terminal activation delay (TAD) and extent of negative T waves in precordial leads
  4. arrhythmias in the ECG, 24-hour Holter ECG recording, ergospirometry and ICD readings
  5. physical capacity (pVO2) assessed on the basis of ergospirometric tests
  6. hospitalization for symptoms of heart failure
  7. sudden cardiac death

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 3

Entresto 97 mg/103 mg film-coated tablets

PRD3417299 · Product

Active substance
Valsartan
Pharmaceutical form
FILM-COATED TABLET
Route of administration
ORAL
Max daily dose
97 mg milligram(s)
Max total dose
194 mg milligram(s)
Max treatment duration
48 Week(s)
Authorisation status
Authorised
ATC code
C09DX04 — -
Marketing authorisation
EU/1/15/1058/005
MA holder
NOVARTIS EUROPHARM LIMITED
MA country
EU
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Entresto 24 mg/26 mg film-coated tablets

PRD3417298 · Product

Active substance
Valsartan
Pharmaceutical form
FILM-COATED TABLET
Route of administration
ORAL
Max daily dose
24 mg milligram(s)
Max total dose
48 mg milligram(s)
Max treatment duration
48 Month(s)
Authorisation status
Authorised
ATC code
C09DX04 — -
Marketing authorisation
EU/1/15/1058/001
MA holder
NOVARTIS EUROPHARM LIMITED
MA country
EU
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Entresto 49 mg/51 mg film-coated tablets

PRD3417302 · Product

Active substance
Valsartan
Pharmaceutical form
FILM-COATED TABLET
Route of administration
ORAL
Max daily dose
49 mg milligram(s)
Max total dose
98 mg milligram(s)
Max treatment duration
48 Week(s)
Authorisation status
Authorised
ATC code
C09DX04 — -
Marketing authorisation
EU/1/15/1058/002
MA holder
NOVARTIS EUROPHARM LIMITED
MA country
EU
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Narodowy Instytut Kardiologii Stefana Kardynala Wyszynskiego Panstwowy Instytut Badawczy

8 Total trials 3 Recruiting 2 Ended
Academic / Non-commercial
Sponsor organisation
Narodowy Instytut Kardiologii Stefana Kardynala Wyszynskiego Panstwowy Instytut Badawczy
Address
Alpejska 42
City
Warsaw
Postcode
04-628
Country
Poland

Scientific contact point

Organisation
Narodowy Instytut Kardiologii Stefana Kardynala Wyszynskiego Panstwowy Instytut Badawczy
Contact name
Clinical Research Support Centre Information Desk

Public contact point

Organisation
Narodowy Instytut Kardiologii Stefana Kardynala Wyszynskiego Panstwowy Instytut Badawczy
Contact name
Clinical Research Support Centre Information Desk

Third parties 1

OrganisationCity, countryDuties
Scientia Research Institute Sp. z o.o.
ORG-100047497
 Bydgoszcz, Poland On site monitoring, Code 12, Code 5, Data management, Code 8

Locations

1 EU/EEA country · 8 investigational sites

By country

CountryMS statusPlanned subjectsSites
Poland Ongoing, recruiting 120 8
Rest of world — 0 —

Investigational sites

Poland

8 sites · Ongoing, recruiting
Samodzielny Publiczny Zaklad Opieki Zdrowotnej Centralny Szpital Kliniczny Uniwersytetu Medycznego W Lodzi
Klinika Elektrokardiologii UM, Ul. Pomorska Nr 251, 92-213, Lodz
Uniwersyteckie Centrum Kliniczne Warszawskiego Uniwersytetu Medycznego
Klinika Kardiologii, Ul. Ulica Stefana Banacha 1a, 02-097, Warsaw
Uniwersytecki Szpital Kliniczny W Poznaniu
Oddział Kardiologii, Ul. Dluga 1/2, 61-848, Poznan
Slaskie Centrum Chorob Serca W Zabrzu
I oddział Kardiologii i Angiologii, Ul. Marii Curie-Sklodowskiej 9, 41-800, Zabrze
Narodowy Instytut Kardiologii Stefana Kardynala Wyszynskiego Panstwowy Instytut Badawczy
Klinika Wad Wrodzonych Serca, Alpejska 42, 04-628, Warsaw
Uniwersyteckie Centrum Kliniczne
Klinika kardiologii i elektroterapii serca, Ul. Mariana Smoluchowskiego 17, 80-214, Gdansk
Krakowski Szpital Specjalistyczny Im. Sw. Jana Pawla II
Oddział Kliniczny Elektrokardiologii, Ul. Pradnicka 80, 31-202, Cracow
Gornoslaskie Centrum Medyczne Im Prof. Leszka Gieca Sląskiego Uniwersytetu Medycznego W Katowicach
I Oddział Kardiologii, Ul. Ziolowa 45/47, 40-635, Katowice

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Country Trial startTrial end Recruitment startRecruitment end Early termination
Poland 2023-07-10 2023-07-10

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 7 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

TypeTitleVersion
Protocol (for publication) D1_Protocol_EU CT Number 2024-157412-29_redacted 2.5
Protocol (for publication) D1_Signature page protocol redacted 2.4
Protocol (for publication) D4_Patient facing documents QoL EQ5D 1
Recruitment arrangements (for publication) K1_Recruitment arrangements ARNI-ARVC 1
Subject information and informed consent form (for publication) L1_SIS and ICF_redacted 2.1
Summary of Product Characteristics (SmPC) (for publication) E2_SmPC Entresto n/a
Synopsis of the protocol (for publication) D1_Protocol synopsis 2024-517412-29-00 2.3

Application history

2 submissions — initial application plus substantial / non-substantial modifications

#TypeCodeSubmittedReference MSConclusionDecision date
1 INITIAL IN 2024-09-09 Poland Acceptable
2024-10-28
 2024-10-31
2 SUBSTANTIAL MODIFICATION SM-1 2025-01-31 Poland Acceptable
2025-05-04
 2025-05-09