randOmized stUdy Using acceleromeTry to Compare Sacubitril/valsarTan and Enalapril in Patients With Heart Failure

NCT ID: NCT02900378

Last Updated: 2020-09-02

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 621 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-12-20
• Study Completion Date: 2018-04-11

Brief Summary

The purpose of this randomized, actively controlled, double-blind study with prospective data collection was to assess differences between sacubitril/valsartan versus enalapril in increasing exercise capacity and non-sedentary physical activity in HFrEF patients. Physical activity was assessed by the 6 minute walk test, and daily physical activity was continuously measured by means of a wrist-worn accelerometry device from 2 weeks before until 12 weeks after start of study therapy (sacubitril/valsartan or enalapril).

Conditions

Chronic Heart Failure With Reduced Ejection Fraction

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

LCZ696 (Sacubitril/Valsartan)

After randomization, patients in this arm received LCZ696 (Sacubitril/Valsartan) twice daily and matching placebo of Enalapril depending on the patient's previous ACEI/ARB dose (enalapril equivalent dose) for 2 weeks. Patients could start study medication at dose level 1 (24 mg/26 mg LCZ), 2 (49 mg/51 mg LCZ) or 2a (49 mg/51 mg LCZ) or matching placebo bid. After 2 weeks (visit 3) the doses were up-titrated: patients, who started on dose level 2 or 2a received the target dose of study medication (level 3) at this point. After another 2 weeks (visit 4) all patients were to achieve the target dose of 97 mg/103 mg bid LCZ696(sacubitril/valsartan) and matching placebo, provided no safety and tolerability issues arised during uptitration.

Group Type: EXPERIMENTAL

LCZ696 (Sacubitril/Valsartan)

Intervention Type: DRUG

LCZ696 (sacubitril/valsartan) was available in 24 mg/26 mg, 49 mg/51 and 97 mg/103 mg mg film-coated tablets

Placebo of Enalapril

Intervention Type: DRUG

Placebo of Enalapril was available to match 2.5 mg, 5 mg and 10 mg film-coated tablets

Enalapril

After randomization, patients in this arm received Enalapril twice daily and matching placebo of LCZ696 (Sacubitril/Valsartan) depending on the patient's previous ACEI/ARB for 2 weeks. Patients could start study medication at dose level 1 or 2a or matching placebo bid. After 2 weeks (visit 3) the doses were up-titrated: patients, who started on dose level 2 or 2a received the target dose of study medication (level 3) at this point. After another 2 weeks (visit 4) all patients were to achieve the target dose of 10 mg bid enalapril and matching placebo, provided no safety and tolerability issues arised during uptitration

Group Type: ACTIVE_COMPARATOR

Placebo of LCZ696 (Sacubitril/Valsartan)

Intervention Type: DRUG

Placebo of LCZ696 (sacubitril/valsartan) was available to match 24 mg/26 mg, 49 mg/51 and 97 mg/103 mg mg film-coated tablets

Enalapril

Intervention Type: DRUG

Enalapril was available in 2.5 mg, 5 mg and 10 mg film-coated tablets

Interventions

LCZ696 (Sacubitril/Valsartan)

LCZ696 (sacubitril/valsartan) was available in 24 mg/26 mg, 49 mg/51 and 97 mg/103 mg mg film-coated tablets

Intervention Type: DRUG

Placebo of LCZ696 (Sacubitril/Valsartan)

Placebo of LCZ696 (sacubitril/valsartan) was available to match 24 mg/26 mg, 49 mg/51 and 97 mg/103 mg mg film-coated tablets

Intervention Type: DRUG

Enalapril

Enalapril was available in 2.5 mg, 5 mg and 10 mg film-coated tablets

Intervention Type: DRUG

Placebo of Enalapril

Placebo of Enalapril was available to match 2.5 mg, 5 mg and 10 mg film-coated tablets

Intervention Type: DRUG

Other Intervention Names

LCZ696; Placebo; Placebo

Eligibility Criteria

Inclusion Criteria

• Written informed consent obtained before any study assessment is performed.
• Ambulatory ≥ 18 years of age with a diagnosis of chronic symptomatic HF (NYHA class ≥ II) with reduced ejection fraction, defined as known LVEF ≤ 40%

AND one of the following two criteria:

• Plasma NT-proBNP level of ≥ 300 pg/mL or BNP ≥ 100 pg/mL (measurement may be recorded no longer than past 12 months) OR
• Confirmation of a heart failure hospitalization last 12 months.
• Patients must be on stable HF medication for at least 4 weeks prior to Week - 2, where the minimal daily dose of current evidence based therapies is equivalent to at least 2.5 mg/d enalapril
• Willingness to wear the accelerometer wristband continuously for the duration of the trial.
• Patients must be living in a setting, allowing them to move about freely and where they are primarily self-responsible for scheduling their sleep and daily activities.

Exclusion Criteria

• History of hypersensitivity to any of the study drugs or their excipients or to drugs of similar chemical classes
• Use of sacubitril/valsartan prior to week - 2.
• Bedridden patients, or patients with significantly impaired/limited physical activity and/or fatigue due to medical conditions other than HF, such as, but not limited to angina (chest pain at exertion), arthritis, gout, peripheral artery occlusive disease, obstructive or restrictive lung disease, malignant disease, neurological disorders (e.g. Parkinson's or Alzheimer's disease, central and peripheral neuroinflammatory and -degenerative disorders or functional central nervous lesions due to hemodynamic or traumatic incidents), injuries (incl. diabetic foot ulcers) or missing limbs
• Patients with palsy, tremor or rigor affecting the non-dominant arm.
• Patients with any skin or other condition of the non-dominant arm that would limit the ability to wear the actigraphy device continuously (24h/day) over 14 weeks.
• Patients fully depending on a mobility support system, e.g. wheelchair, scooter or walker. Patients are allowed to use a cane as long as this is not used with the non-dominant arm.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Novartis Pharmaceuticals

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Novartis Pharmaceuticals

Role: STUDY_DIRECTOR

Novartis Pharmaceuticals

Locations

Novartis Investigative Site

Edegem, Antwerpen, Belgium

Novartis Investigative Site

Dendermonde, , Belgium

Novartis Investigative Site

Geel, , Belgium

Novartis Investigative Site

Ghent, , Belgium

Novartis Investigative Site

Turnhout, , Belgium

Novartis Investigative Site

Pleven, , Bulgaria

Novartis Investigative Site

Plovdiv, , Bulgaria

Novartis Investigative Site

Sofia, , Bulgaria

Novartis Investigative Site

Sofia, , Bulgaria

Novartis Investigative Site

Sofia, , Bulgaria

Novartis Investigative Site

Brno, Czech Republic, Czechia

Novartis Investigative Site

Chomutov, Czech Republic, Czechia

Novartis Investigative Site

Svitavy, Czech Republic, Czechia

Novartis Investigative Site

Most, CZE, Czechia

Novartis Investigative Site

Kolín, , Czechia

Novartis Investigative Site

Prague, , Czechia

Novartis Investigative Site

Prague, , Czechia

Novartis Investigative Site

Elsinore, , Denmark

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Odense C, , Denmark

Novartis Investigative Site

Randers, , Denmark

Novartis Investigative Site

Roskilde, , Denmark

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Svendborg, , Denmark

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Tallinn, , Estonia

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Tallinn, , Estonia

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Tartu, , Estonia

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Hämeenlinna, , Finland

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Tampere, , Finland

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Auxerre, , France

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Clermont-Ferrand, , France

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Metz-Tessy, , France

Novartis Investigative Site

Dresden, Saxony, Germany

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Bad Homburg, , Germany

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Berlin, , Germany

Novartis Investigative Site

Berlin, , Germany

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Berlin, , Germany

Novartis Investigative Site

Berlin, , Germany

Novartis Investigative Site

Buchholz in der Nordheide, , Germany

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Dietzenbach, , Germany

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Elsterwerda, , Germany

Novartis Investigative Site

Essen, , Germany

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Frankfurt, , Germany

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Halberstadt, , Germany

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Hamburg, , Germany

Novartis Investigative Site

Haßloch, , Germany

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Leipzig, , Germany

Novartis Investigative Site

Löhne, , Germany

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Mannheim, , Germany

Novartis Investigative Site

Mühldorf, , Germany

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Nuremberg, , Germany

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Reinfeld, , Germany

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Schwäbisch Hall, , Germany

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Siegen, , Germany

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Wallerfing, , Germany

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Wedel, , Germany

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Wermsdorf, , Germany

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Alexandroupoli, Evros, Greece

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Heraklion Crete, Greece, Greece

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Voula, GR, Greece

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Athens, , Greece

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Athens, , Greece

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Kopavogur, , Iceland

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Reykjavik, , Iceland

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Dublin, , Ireland

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Jelgava, , Latvia

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Ogre, , Latvia

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Riga, , Latvia

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Riga, , Latvia

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Riga, , Latvia

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Kaunas, LTU, Lithuania

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Klaipėda, LTU, Lithuania

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Vilnius, , Lithuania

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Goes, , Netherlands

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Haarlem, , Netherlands

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Heerlen, , Netherlands

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Leiderdorp, , Netherlands

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Roermond, , Netherlands

Novartis Investigative Site

Veldhoven, , Netherlands

Novartis Investigative Site

Feiring, , Norway

Novartis Investigative Site

Warsaw, Masovian Voivodeship, Poland

Novartis Investigative Site

Warsaw, , Poland

Novartis Investigative Site

Warsaw, , Poland

Novartis Investigative Site

Warsaw, , Poland

Novartis Investigative Site

Lodz, Łódź Voivodeship, Poland

Novartis Investigative Site

Ferrol, A Coruna, Spain

Novartis Investigative Site

Elche, Alicante, Spain

Novartis Investigative Site

Córdoba, Andalusia, Spain

Novartis Investigative Site

Granada, Andalusia, Spain

Novartis Investigative Site

Huelva, Andalusia, Spain

Novartis Investigative Site

Sanlúcar de Barrameda, Andalusia, Spain

Novartis Investigative Site

Seville, Andalusia, Spain

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Villamartín, Cadiz, Spain

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Santander, Cantabria, Spain

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Aranda de Duero, Castille and León, Spain

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Burgos, Castille and León, Spain

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León, Castille and León, Spain

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Soria, Castille and León, Spain

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Sabadell, Catalonia, Spain

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Cáceres, Extremadura, Spain

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Lugo, Galicia, Spain

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Santiago de Compostela, Galicia, Spain

Novartis Investigative Site

Gijón, Principality of Asturias, Spain

Novartis Investigative Site

Oviedo, Principality of Asturias, Spain

Novartis Investigative Site

Alicante, Valencia, Spain

Novartis Investigative Site

Manises, Valencia, Spain

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Barcelona, , Spain

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Girona, , Spain

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Madrid, , Spain

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Madrid, , Spain

Novartis Investigative Site

Lund, , Sweden

Novartis Investigative Site

Mölndal, , Sweden

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Stockholm, , Sweden

Novartis Investigative Site

Stockton-on-Tees, Cleveland, United Kingdom

Novartis Investigative Site

Rothwell, GBR, United Kingdom

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Faringdon, Oxfordshire, United Kingdom

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Gateshead, Tyne and Wear, United Kingdom

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Bournemouth, , United Kingdom

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Cumbria, , United Kingdom

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Poole, , United Kingdom

Novartis Investigative Site

Wellingborough, , United Kingdom

Countries

Belgium; Bulgaria; Czechia; Denmark; Estonia; Finland; France; Germany; Greece; Iceland; Ireland; Latvia; Lithuania; Netherlands; Norway; Poland; Spain; Sweden; United Kingdom

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2016-003085-32

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CLCZ696B3301

Identifier Type: -

Identifier Source: org_study_id