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

NCT02661217 | Completed Phase 4 Results DMC FDA Drug

• 2 other identifiers: CLCZ696B24012015-003266-87
• Study Type: interventional
• Target: 1,002
• Locations: 19 countries
• Sites: 152

Brief Summary

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

Conditions

Heart Failure With Reduced Ejection Fraction

Keywords

Acute decompensated heart failure; Reduced ejection fraction; Pre-discharge treatment; Post-discharge treatment; Angiotensin receptor neprilysine inhibitor; HFrEF

Outcome Measures

Primary Outcomes (1)

• Percentage of Patients Achieving the Target Dose of LCZ696 200 mg Bid at 10 Weeks Post Randomization

  Percentage of patients achieving and maintaining LCZ696 200 mg bid for at least 2 weeks leading to Week 10

  10 weeks after Randomization

Secondary Outcomes (3)

• Percentage of Patients Achieving and Maintaining Either LCZ696 100 mg and/or 200 mg Bid

  10 weeks after Randomization

• Percentage of Patients Achieving and Maintaining Any Dose of LCZ696

  10 weeks after Randomization

• Percentage of Patients Permanently Discontinued From Treatment

  10 weeks after Randomization AND 26 weeks after randomization

Study Arms (2)

Pre-discharge treatment initiation

OTHER

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

Drug: LCZ696

Post-discharge treatment initiation

OTHER

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

Drug: LCZ696

Interventions

LCZ696 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; Pre-discharge treatment initiation

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

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

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (152)

Novartis Investigative Site

Quilmes, Buenos Aires, B1878DKF, Argentina

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Novartis Investigative Site

Villa María, Córdoba Province, X5900JKA, Argentina

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Novartis Investigative Site

Buenos Aires, C1405CNF, Argentina

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Novartis Investigative Site

Buenos Aires, C1426BOR, Argentina

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Novartis Investigative Site

Córdoba, X5000, Argentina

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Novartis Investigative Site

Salta, 4400, Argentina

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Novartis Investigative Site

San Miguel de Tucumán, T4000NIJ, Argentina

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Novartis Investigative Site

Brussels, 1200, Belgium

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Novartis Investigative Site

Genk, 3600, Belgium

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Novartis Investigative Site

Huy, 4500, Belgium

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Novartis Investigative Site

Leuven, 3000, Belgium

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Novartis Investigative Site

Ronse, 9600, Belgium

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Novartis Investigative Site

Vancouver, British Columbia, V5Z 1M9, Canada

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Novartis Investigative Site

Hamilton, Ontario, L8L 2X2, Canada

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Novartis Investigative Site

Montreal, Quebec, H3A 1A1, Canada

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Novartis Investigative Site

Montreal, Quebec, H3T 1E2, Canada

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Novartis Investigative Site

Brno, Czech Republic, 656 91, Czechia

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Novartis Investigative Site

Karlovy Vary, Czech Republic, 360 66, Czechia

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Novartis Investigative Site

Liberec, Czech Republic, 460 63, Czechia

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Novartis Investigative Site

Tábor, Czech Republic, 39003, Czechia

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Novartis Investigative Site

Třebíč, Czech Republic, 674 01, Czechia

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Novartis Investigative Site

Beroun, CZE, 26601, Czechia

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Novartis Investigative Site

Ostrava, CZE, 72880, Czechia

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Novartis Investigative Site

Brno-Bohunice, 625 00, Czechia

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Novartis Investigative Site

Jihlava, 586 01, Czechia

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Novartis Investigative Site

Kolín, 280 20, Czechia

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Novartis Investigative Site

Olomouc, 775 20, Czechia

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Novartis Investigative Site

Prague, 100 34, Czechia

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Novartis Investigative Site

Prague, 12808, Czechia

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Novartis Investigative Site

Slaný, 274 01, Czechia

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Novartis Investigative Site

Amiens, 80054, France

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Besançon, 25030, France

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Paris, 75010, France

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Paris, 75012, France

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Toulouse, 31059, France

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Tourcoing, 59200, France

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Valenciennes, 59300, France

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Mannheim, Baden-Wurttemberg, 68305, Germany

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Regensburg, Bavaria, 93053, Germany

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Leverkusen, North Rhine-Westphalia, 51375, Germany

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Berlin, 13353, Germany

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Dortmund, 44379, Germany

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Erfurt, 99089, Germany

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Essen, 45356, Germany

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Frankfurt, 65929, Germany

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Göttingen, 37075, Germany

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Hamburg, 20246, Germany

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Jena, 07740, Germany

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Koeln-Nippes, 50733, Germany

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Langen, 63225, Germany

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Lübeck, 23569, Germany

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Magdeburg, 39120, Germany

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Mainz, 55131, Germany

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Mönchengladbach, 41063, Germany

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Neuwied, 56564, Germany

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Oldenburg, 26133, Germany

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Rüsselsheim am Main, 65428, Germany

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Witten, 58455, Germany

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Bergamo, BG, 24127, Italy

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Cremona, CR, 26100, Italy

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Roma, RM, 00152, Italy

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Milan, 20142, Italy

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El Chouf, LBN, 1503201002, Lebanon

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Beirut, 1107 2020, Lebanon

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Beirut, Lebanon

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El Achrafiyé, 166830, Lebanon

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Saida, 652, Lebanon

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Ålesund, NO-6026, Norway

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Bergen, 5009, Norway

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Grålum, 1714, Norway

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Lillehammer, 2629, Norway

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Bialystok, 15-276, Poland

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Krakow, 31202, Poland

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Poznan, 61-848, Poland

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Puławy, 24100, Poland

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Warsaw, 04-749, Poland

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Wroclaw, 50 420, Poland

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Lodz, Łódź Voivodeship, 90 549, Poland

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Vila Real, Portuigal, 5000-508, Portugal

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Amadora, 2720-276, Portugal

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Aveiro, 3814-501, Portugal

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Coimbra, 3000-075, Portugal

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Covilha, 6200-251, Portugal

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Guimarães, 4835-044, Portugal

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Leiria, 2410-187, Portugal

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Lisbon, 1495 005, Portugal

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Lisbon, 1500 650, Portugal

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Lisbon, 1649-035, Portugal

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Porto, 4099-001, Portugal

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Porto, 4200-319, Portugal

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Novartis Investigative Site

Gatchina, 188300, Russia

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Kazan', 420012, Russia

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Moscow, 117292, Russia

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Moscow, 117556, Russia

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Moscow, 123182, Russia

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Saint Petersburg, 193312, Russia

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Saint Petersburg, 199106, Russia

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Yaroslavl, 150047, Russia

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Dammam, 31463, Saudi Arabia

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Jeddah, 21499, Saudi Arabia

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Riyadh, 11211, Saudi Arabia

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Dunajská Streda, Slovak Republic, 92901, Slovakia

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Košice, Slovak Republic, 4190, Slovakia

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Liptovský Mikuláš, Slovak Republic, 031 23, Slovakia

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Bratislava, 826 06, Slovakia

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Bratislava, 833 48, Slovakia

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Dolný Kubín, 026 01, Slovakia

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Martin, 036 59, Slovakia

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Prešov, 080 01, Slovakia

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Rimavská Sobota, 97912, Slovakia

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Trnava, 917 75, Slovakia

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Málaga, Andalusia, 29010, Spain

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Sanlúcar de Barrameda, Andalusia, 11540, Spain

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Seville, Andalusia, 41009, Spain

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Seville, Andalusia, 41014, Spain

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Barcelona, Barcelona/ Cataluny/Espanya, 08035, Spain

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Villamartín, Cadiz, 11650, Spain

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A Coruña, Galicia, 15006, Spain

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Olot, Girona, 17800, Spain

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Móstoles, Madrid, 28935, Spain

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El Palmar, Murcia, 30120, Spain

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Valencia, Valencia, 46010, Spain

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Valencia, Valencia, 46014, Spain

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Valencia, Valencia, 46026, Spain

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Las Palmas de Gran Canaria, 35010, Spain

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Madrid, 28222, Spain

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Gothenburg, 413 45, Sweden

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Novartis Investigative Site

Jönköping, 551 85, Sweden

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Basel, 4031, Switzerland

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Geneva, 1211, Switzerland

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Novartis Investigative Site

Eskişehir, Meselik, 26480, Turkey (Türkiye)

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Ankara, 06100, Turkey (Türkiye)

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Istanbul, 34304, Turkey (Türkiye)

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Kocaeli, 41380, Turkey (Türkiye)

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Mersin, 33343, Turkey (Türkiye)

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Sivas, 58140, Turkey (Türkiye)

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Westcliff-on-Sea, Essex, SS0 0RY, United Kingdom

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Basingstoke, Hampshire, RG24 9NA, United Kingdom

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Ashford, Kent, TN24 0LZ, United Kingdom

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Bridgend, Mid Glamorgan, CF31 1RQ, United Kingdom

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Portadown, Nothern Ireland, BT63 5QQ, United Kingdom

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Sunderland, Tyne and Wear, SR4 7TP, United Kingdom

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Blackpool, FY3 8NR, United Kingdom

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Leeds, LS1 3EX, United Kingdom

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Leicester, LE 3 9QP, United Kingdom

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Liverpool, L9 7AL, United Kingdom

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London, EC14 7BE, United Kingdom

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Middlesbrough, TS4 3BW, United Kingdom

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Newcastle upon Tyne, NE1 4LP, United Kingdom

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Norwich, NR4 7UY, United Kingdom

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Swindon, SN3 6BB, United Kingdom

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York, YO31 8HE, United Kingdom

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Related Publications (5)

• 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.

  PMID: 37678704 DERIVED

• 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.

  PMID: 32800508 DERIVED

• 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.

  PMID: 31820537 DERIVED

• 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.

  PMID: 31134724 DERIVED

• 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.

  PMID: 29239515 DERIVED

MeSH Terms

Interventions

sacubitril and valsartan sodium hydrate drug combination

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

novartis.email@novartis.com

862-778-8300

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: SUPPORTIVE CARE
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 19, 2016
• First Posted: January 22, 2016
• Study Start: February 12, 2016
• Primary Completion: February 20, 2018
• Study Completion: June 20, 2018
• Last Updated: April 26, 2021
• Results First Posted: April 26, 2021

Record last verified: 2021-03

Data Sharing

• IPD Sharing: Will not share

Locations

AR (7); LE (5); TU (6); FR (7); BE (5); RU (8); NO (4); GB (16); ES (15); SA (3); CA (4); PT (12); PL (7); DE (21); SL (10); CH (2); CZ (14); IT (4); SE (2)