The effect of sacubitril/valsartan versus ramipril on left ventricular function and remodeling in patients with ischemic heart failure with mid-range ejection fraction.

2024-518239-12-00 Protocol DW.0701.005.2020P Therapeutic confirmatory (Phase III) Ongoing, recruiting

Start 26 Jan 2023 · Status Ongoing, recruiting · 1 EU/EEA countries · 6 sites · Protocol DW.0701.005.2020P

Overview

Sponsor-declared trial summary

Phase Therapeutic confirmatory (Phase III)
Status Ongoing, recruiting
Participants planned 666
Countries 1
Sites 6

heart failure with moderately reduced ejection fraction (HFmrEF)

The purpose of the study is to evaluate the effect of sacubitril / valsartan versus ramipril on left ventricular remodeling and function in ischemic HFmrEF patients. The primary objective of the study is to evaluate the effect of sacubitril / valsartan versus ramipril on the change in left ventricular end-systolic volu…

Key facts

Sponsor
Krakowski Szpital Specjalistyczny Im. Sw. Jana Pawla II
Participant type
Patients
Age range
18-64 years, 65+ years
Gender
Male and Female
Therapeutic area
Diseases [C] - Cardiovascular Diseases [C14]
Trial duration
26 Jan 2023 → ongoing
Decision date (initial)
2024-12-16
Transition trial
Yes
Low-intervention
No
Rare-disease indication
No
Vulnerable population
Yes
Funding sources
Agencja Badań Medycznych

External identifiers

EU CT number
2024-518239-12-00
EudraCT number
2020-005302-26
ClinicalTrials.gov
NCT05508035

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Safety, Efficacy

The purpose of the study is to evaluate the effect of sacubitril / valsartan versus ramipril on left ventricular remodeling and function in ischemic HFmrEF patients.
The primary objective of the study is to evaluate the effect of sacubitril / valsartan versus ramipril on the change in left ventricular end-systolic volume as measured by magnetic resonance imaging (MRI) in patients with ischemic HFmrEF after 12 months of treatment.

Secondary objectives 10

  1. Assessment of the effect of sacubitril / valsartan compared to ramipril on 1. change in left ventricular end-diastolic volume measured by MRI
  2. change in indexed left ventricular end-systolic and end-diastolic volumes measured by MRI
  3. change in left ventricular ejection fraction measured by MRI
  4. occurrence of the endpoint of death from cardiovascular causes or first hospitalization for HF
  5. the occurrence of the endpoint of death from cardiovascular causes or first or subsequent hospitalization for HF
  6. occurrence of death from cardiovascular causes
  7. first hospitalization due to HF
  8. occurrence of the first or subsequent hospitalization due to HF
  9. time to death from cardiovascular causes or first hospitalization for HF
  10. occurrence of death from any cause in patients with ischemic HFmrEF over a 12 month treatment period

Conditions and MedDRA coding

heart failure with moderately reduced ejection fraction (HFmrEF)

VersionLevelCodeTermSystem organ class
20.0 LLT 10010684 Congestive heart failure 10007541

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

  1. Written consent to participate in the study, expressed prior to any procedures related to the study.
  2. Age 18 and over.
  3. Symptomatic HF in NYHA class II to IV of ischemic etiology at screening visit.
  4. Left ventricular ejection fraction at screening visit ranged from 40- 49%, confirmed by echocardiography at a randomization visit.
  5. Elevated concentration of NT-proBNP natriuretic peptide≥125 pg / ml at screening visit(if sinus rhythm during the visit).
  6. Elevated NT-proBNP natriuretic peptide concentration≥350 pg/ml at the screening visit (if atrial fibrillation or flutter during the visit).
  7. Features of a structural / functional disease of the left ventricle.
  8. Optimal pharmacotherapy with ACEI or ARB and beta-blocker, unless they are contraindicated.

Exclusion criteria 12

  1. History of hypersensitivity or allergy to any of the drugs tested or drugs of similar chemical class, ACEIs, ARBs or neprilysin inhibitors.
  2. Previous history of intolerance to recommended ACEI or ARB target doses.
  3. Known history of angioedema.
  4. Requirement of simultaneous treatment with ACEI and ARB.
  5. Acute decompensated HF within 6 weeks prior to screening visit.
  6. Symptomatic hypotension systolic blood pressure <95 mmHg at screening visit.
  7. Current or previous treatment with sacubitril / valsartan not related to participation in the clinical trial.
  8. Estimated creatinine clearance <30 ml / min / 1,73 m2 at screening visit.
  9. Serum potassium >5.2 mmol / L at screening visit.
  10. Acute coronary syndrome or elective revascularization within 6 weeks prior to screening.
  11. Stroke, transient ischemic attack, carotid angioplasty, heart surgery, or any other major cardiovascular surgery in the 3 months prior to screening.
  12. Implantation of a cardioverter defibrillator, pacemaker, or resynchronization therapy device incompatible with MRI.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

  1. Change in left ventricular end-systolic volume after 12 months of treatment as measured by MRI.

Secondary endpoints 10

  1. Change in left ventricular end-diastolic volume measured by MRI in patients with ischemic HFmrEF after 12 months of treatment.
  2. Change in indexed left ventricular end-systolic and end-diastolic volumes measured by MRI in patients with ischemic HFmrEF after 12 months of treatment.
  3. Change in left ventricular ejection fraction measured by MRI in patients with ischemic HFmrEF after 12 months of treatment.
  4. Death from cardiovascular causes or first hospitalization due to HF in patients with ischemic HFmrEF over a 12 month treatment period.
  5. Death from cardiovascular causes or first or subsequent hospitalization due to HF in patients with ischemic HFmrEF over a 12 month treatment period.
  6. Death from cardiovascular causes in patients with ischemic HFmrEF over a 12 month treatment period.
  7. First hospitalization for HF in patients with ischemic HFmrEF over a 12 month treatment period.
  8. First or subsequent hospitalization for HF in patients with ischemic HFmrEF over a 12 month treatment period.
  9. Number of days until death from cardiovascular causes or first hospitalization for HF in patients with ischemic HFmrEF over a 12 month treatment period.
  10. All-cause death in patients with ischemic HFmrEF over a 12 month treatment period.

Investigational products

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

Test 1

Valsartan

SCP77807446 · ATC

Active substance
Valsartan
Route of administration
ORAL USE
Max daily dose
400 mg milligram(s)
Max total dose
151200 mg milligram(s)
Max treatment duration
54 Week(s)
Authorisation status
Authorised
ATC code
C09DX04 — VALSARTAN AND SACUBITRIL
Marketing authorisation
-
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
Yes
Modification description
Taking the tablets from the blisters and repacking into HDPE bottles with a capacity of 70 ml

Comparator 1

Hydrochlorothiazide

SCP10361725 · ATC

Active substance
Hydrochlorothiazide
Route of administration
ORAL USE
Max daily dose
10 mg milligram(s)
Max total dose
3780 mg milligram(s)
Max treatment duration
54 Week(s)
Authorisation status
Authorised
ATC code
C09AA05 — RAMIPRIL
Marketing authorisation
-
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
Yes
Modification description
Taking the tablets from the blisters and repacking into HDPE bottles with a capacity of 70 ml

Placebo 2

Placebo to VALSARTAN AND SACUBITRIL PL1 PL2

N/A · Product

Other product name
N/A
Pharmaceutical form
N/A
ATC code
N/A — N/A
Marketing authorisation
N/A
MA holder
N/A
MA country
Iceland
Paediatric formulation
No

Placebo to RAMIPRIL PL3 PL4

N/A · Product

Other product name
N/A
Pharmaceutical form
N/A
ATC code
N/A — N/A
Marketing authorisation
N/A
MA holder
N/A
MA country
Iceland
Paediatric formulation
No

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Krakowski Szpital Specjalistyczny Im. Sw. Jana Pawla II

Sponsor organisation
Krakowski Szpital Specjalistyczny Im. Sw. Jana Pawla II
Address
Ul. Pradnicka 80
City
Cracow
Postcode
31-202
Country
Poland

Scientific contact point

Organisation
Krakowski Szpital Specjalistyczny Im. Sw. Jana Pawla II
Contact name
Co-ordinating Investigator

Public contact point

Organisation
Krakowski Szpital Specjalistyczny Im. Sw. Jana Pawla II
Contact name
Dział Badań

Third parties 1

OrganisationCity, countryDuties
50Bio.Com Sp. z o.o.
ORG-100050106
 Warsaw, Poland On site monitoring, Code 12, Code 5

Locations

1 EU/EEA country · 6 investigational sites

By country

CountryMS statusPlanned subjectsSites
Poland Ongoing, recruiting 666 6
Rest of world — 0 —

Investigational sites

Poland

6 sites · Ongoing, recruiting
Medicome Sp. z o.o.
Medicome Sp. z o.o., Plac Tadeusza Kosciuszki 12, 32-600, Oswiecim
Uniwersytecki Szpital Kliniczny Im. Wojskowej Akademii Medycznej Uniwersytetu Medycznego W Lodzi Centralny Szpital Weteranow SPZOZ
Zakład Kardiologii Nieinwazyjnej, Ul. Stefana Zeromskiego 113, 90-549, Lodz
Uniwersytecki Szpital Kliniczny W Opolu
Oddział Kardiologii, Al. Wincentego Witosa 26, 45-401, Opole
Narodowy Instytut Kardiologii Stefana Kardynala Wyszynskiego Panstwowy Instytut Badawczy
Klinika Niewydolności Serca i Transplantologii, Alpejska 42, 04-628, Warsaw
Krakowski Szpital Specjalistyczny Im. Sw. Jana Pawla II
Oddział Kliniczny Choroby Wieńcowej i Niewydolności Serca, Ul. Pradnicka 80, 31-202, Cracow
Slaskie Centrum Chorob Serca W Zabrzu
III Katedra i Oddział Kliniczny Kardiologii w Zabrzu, Ul. Marii Curie-Sklodowskiej 9, 41-800, Zabrze

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 2023-01-26 2023-07-13

Results and documents

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

Documents 8 files

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

TypeTitleVersion
Protocol (for publication) D1_Protocol_2024-518239-12-00 track changes 6.0
Protocol (for publication) D1_Protocol_2024-518239-12-00_blinded 6.0
Recruitment arrangements (for publication) K1_Placeholder_Recruitment Agreements_PL_2024-518239-12-00 NA
Subject information and informed consent form (for publication) L1_ICF_2024-518239-12-00 5.0
Summary of Product Characteristics (SmPC) (for publication) G1_Axtil_SmPC_2024-518239-12-00 NA
Summary of Product Characteristics (SmPC) (for publication) G1_Entresto_SmPC_2024-518239-12-00 NA
Synopsis of the protocol (for publication) D1_Protocol Synopsis_2024-518239-12-00 6.0
Synopsis of the protocol (for publication) D1_Protocol synopsis_placeholder NA

Application history

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

#TypeCodeSubmittedReference MSConclusionDecision date
1 INITIAL IN 2024-10-14 Poland Acceptable
2024-12-09
 2024-12-16
2 SUBSTANTIAL MODIFICATION SM-1 2025-08-28 Poland Acceptable
2025-10-26
 2025-10-29
3 NON SUBSTANTIAL MODIFICATION NSM-1 2026-04-24 Poland Acceptable
2025-10-26
 2026-04-24

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