Comparison of Pre- and Post-discharge Initiation of LCZ696 Therapy in HFrEF Patients After an Acute Decompensation Event

NCT ID: NCT02661217

Last Updated: 2021-04-26

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE4

Total Enrollment

1002 participants

Study Classification

INTERVENTIONAL

Study Start Date

2016-02-12

Study Completion Date

2018-06-20

Brief Summary

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To explore two modalities of treatment initiation (Pre-discharge, and Post-discharge) with LCZ696 in HFrEF patients following stabilization after an ADHF episode.

Detailed Description

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Conditions

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Heart Failure With Reduced Ejection Fraction

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

SUPPORTIVE_CARE

Blinding Strategy

SINGLE

Outcome Assessors

Study Groups

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Pre-discharge treatment initiation

Patients received first dose at any point after Randomization but no later than 12 h before discharge.

Group Type OTHER

LCZ696

Intervention Type DRUG

LCZ696 film-coated tables were supplied to the investigators. Tablets were taken with a glass of water, and were administered with or without food.

The target dose of LCZ696 was 200 mg twice daily. Starting dose of LCZ696 was either 50 or 100 mg, twice daily. The dose of LCZ696 should be doubled every 2-4 weeks to achieve the target dose of 200 mg twice daily, as tolerated by the patient.

Post-discharge treatment initiation

Patients received first dose after discharge and up to 14 days thereafter.

Group Type OTHER

LCZ696

Intervention Type DRUG

LCZ696 film-coated tables were supplied to the investigators. Tablets were taken with a glass of water, and were administered with or without food.

The target dose of LCZ696 was 200 mg twice daily. Starting dose of LCZ696 was either 50 or 100 mg, twice daily. The dose of LCZ696 should be doubled every 2-4 weeks to achieve the target dose of 200 mg twice daily, as tolerated by the patient.

Interventions

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LCZ696

LCZ696 film-coated tables were supplied to the investigators. Tablets were taken with a glass of water, and were administered with or without food.

The target dose of LCZ696 was 200 mg twice daily. Starting dose of LCZ696 was either 50 or 100 mg, twice daily. The dose of LCZ696 should be doubled every 2-4 weeks to achieve the target dose of 200 mg twice daily, as tolerated by the patient.

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

1. Patients hospitalized due to acute decompensated HF episode (ADHF) as primary diagnosis) and consistent Signs \& Symptoms
2. Diagnosis of HF New York Heart Association class II-to-IV and reduced ejection fraction: Left ventricular ejection fraction ≤ 40% at Screening
3. Patients did not receive any IV vasodilators (except nitrates), and/or any IV inotropic therapy from the time of presentation for ADHF to Randomization
4. Stabilized (while in the hospital) for at least 24 hours leading to Randomization.
5. Meeting one of the following criteria:

* Patients on any dose of ACEI or ARB at screening
* ACEI/ARB naïve patients and patients not on ACEI or ARB for at least 4 weeks before screening.

Exclusion Criteria

1. History of hypersensitivity to the sacubitril, valsartan, or any ARBs, NEP inhibitors or to any of the LCZ696 excipients.
2. Symptomatic hypotension and/or a SBP below 110 mm Hg or SBP above 180 mm Hg prior to randomization
3. End stage renal disease at Screening; or estimated GFR below 30 mL/min/1.73 m2 (as measured by MDRD formula at Randomization.
4. Serum potassium above 5.4 mmol/L at Randomization.
5. Known history of hereditary or idiopathic angioedema or angioedema related to previous ACE inhibitor or ARB therapy
6. Severe hepatic impairment, biliary cirrhosis and cholestasis
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Novartis Pharmaceuticals

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Novartis Pharmaceuticals

Role: STUDY_DIRECTOR

Novartis Pharmaceuticals

Locations

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Novartis Investigative Site

Quilmes, Buenos Aires, Argentina

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Villa María, Córdoba Province, Argentina

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Buenos Aires, , Argentina

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Buenos Aires, , Argentina

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Córdoba, , Argentina

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Salta, , Argentina

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San Miguel de Tucumán, , Argentina

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Brussels, , Belgium

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Genk, , Belgium

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Huy, , Belgium

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Leuven, , Belgium

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Ronse, , Belgium

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Vancouver, British Columbia, Canada

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Hamilton, Ontario, Canada

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Montreal, Quebec, Canada

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Montreal, Quebec, Canada

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Brno, Czech Republic, Czechia

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Karlovy Vary, Czech Republic, Czechia

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Liberec, Czech Republic, Czechia

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Tábor, Czech Republic, Czechia

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Třebíč, Czech Republic, Czechia

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Beroun, CZE, Czechia

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Ostrava, CZE, Czechia

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Brno Bohunice, , Czechia

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Jihlava, , Czechia

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Kolín, , Czechia

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Olomouc, , Czechia

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Prague, , Czechia

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Prague, , Czechia

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Slaný, , Czechia

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Amiens, , France

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Besançon, , France

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Toulouse, , France

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Tourcoing, , France

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Valenciennes, , France

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Mannheim, Baden-Wurttemberg, Germany

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Regensburg, Bavaria, Germany

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Leverkusen, North Rhine-Westphalia, Germany

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Berlin, , Germany

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Dortmund, , Germany

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Erfurt, , Germany

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Essen, , Germany

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Frankfurt, , Germany

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Oldenburg, , Germany

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Rüsselsheim am Main, , Germany

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Witten, , Germany

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Bergamo, BG, Italy

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Cremona, CR, Italy

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Roma, RM, Italy

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Milan, , Italy

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El Chouf, LBN, Lebanon

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Beirut, , Lebanon

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Beirut, , Lebanon

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El Achrafiyé, , Lebanon

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Saida, , Lebanon

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Ålesund, , Norway

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Bergen, , Norway

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Lillehammer, , Norway

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Lodz, Łódź Voivodeship, Poland

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Vila Real, Portuigal, Portugal

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Gatchina, , Russia

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Kazan', , Russia

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Dammam, , Saudi Arabia

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Jeddah, , Saudi Arabia

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Riyadh, , Saudi Arabia

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Dunajská Streda, Slovak Republic, Slovakia

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Valencia, Valencia, Spain

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Valencia, Valencia, Spain

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Las Palmas de Gran Canaria, , Spain

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Madrid, , Spain

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Gothenburg, , Sweden

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Jönköping, , Sweden

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Basel, , Switzerland

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Geneva, , Switzerland

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Eskişehir, Meselik, Turkey (Türkiye)

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Ankara, , Turkey (Türkiye)

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Istanbul, , Turkey (Türkiye)

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Mersin, , Turkey (Türkiye)

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Sivas, , Turkey (Türkiye)

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Westcliff-on-Sea, Essex, United Kingdom

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Basingstoke, Hampshire, United Kingdom

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Ashford, Kent, United Kingdom

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Bridgend, Mid Glamorgan, United Kingdom

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Portadown, Nothern Ireland, United Kingdom

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Sunderland, Tyne and Wear, United Kingdom

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Blackpool, , United Kingdom

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Norwich, , United Kingdom

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Swindon, , United Kingdom

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Countries

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Argentina Belgium Canada Czechia France Germany Italy Lebanon Norway Poland Portugal Russia Saudi Arabia Slovakia Spain Sweden Switzerland Turkey (Türkiye) United Kingdom

References

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Straburzynska-Migaj E, Senni M, Wachter R, Fonseca C, Witte KK, Mueller C, Lonn E, Butylin D, Noe A, Schwende H, Lawrence D, Suryawanshi B, Pascual-Figal D; of TRANSITION Investigators. Early Initiation of Sacubitril/Valsartan in Patients With Acute Heart Failure and Renal Dysfunction: An Analysis of the TRANSITION Study. J Card Fail. 2024 Mar;30(3):425-435. doi: 10.1016/j.cardfail.2023.08.021. Epub 2023 Sep 9.

Reference Type DERIVED
PMID: 37678704 (View on PubMed)

Pascual-Figal D, Wachter R, Senni M, Bao W, Noe A, Schwende H, Butylin D, Prescott MF; TRANSITION Investigators. NT-proBNP Response to Sacubitril/Valsartan in Hospitalized Heart Failure Patients With Reduced Ejection Fraction: TRANSITION Study. JACC Heart Fail. 2020 Oct;8(10):822-833. doi: 10.1016/j.jchf.2020.05.012. Epub 2020 Aug 12.

Reference Type DERIVED
PMID: 32800508 (View on PubMed)

Senni M, Wachter R, Witte KK, Straburzynska-Migaj E, Belohlavek J, Fonseca C, Mueller C, Lonn E, Chakrabarti A, Bao W, Noe A, Schwende H, Butylin D, Pascual-Figal D; TRANSITION Investigators. Initiation of sacubitril/valsartan shortly after hospitalisation for acutely decompensated heart failure in patients with newly diagnosed (de novo) heart failure: a subgroup analysis of the TRANSITION study. Eur J Heart Fail. 2020 Feb;22(2):303-312. doi: 10.1002/ejhf.1670. Epub 2019 Dec 9.

Reference Type DERIVED
PMID: 31820537 (View on PubMed)

Wachter R, Senni M, Belohlavek J, Straburzynska-Migaj E, Witte KK, Kobalava Z, Fonseca C, Goncalvesova E, Cavusoglu Y, Fernandez A, Chaaban S, Bohmer E, Pouleur AC, Mueller C, Tribouilloy C, Lonn E, A L Buraiki J, Gniot J, Mozheiko M, Lelonek M, Noe A, Schwende H, Bao W, Butylin D, Pascual-Figal D; TRANSITION Investigators. Initiation of sacubitril/valsartan in haemodynamically stabilised heart failure patients in hospital or early after discharge: primary results of the randomised TRANSITION study. Eur J Heart Fail. 2019 Aug;21(8):998-1007. doi: 10.1002/ejhf.1498. Epub 2019 May 27.

Reference Type DERIVED
PMID: 31134724 (View on PubMed)

Pascual-Figal D, Wachter R, Senni M, Belohlavek J, Noe A, Carr D, Butylin D. Rationale and design of TRANSITION: a randomized trial of pre-discharge vs. post-discharge initiation of sacubitril/valsartan. ESC Heart Fail. 2018 Apr;5(2):327-336. doi: 10.1002/ehf2.12246. Epub 2017 Dec 14.

Reference Type DERIVED
PMID: 29239515 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

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2015-003266-87

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CLCZ696B2401

Identifier Type: -

Identifier Source: org_study_id

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