Clinical trial NCT02900378: randOmized stUdy Using acceleromeTry to Compare Sacubitril/valsarTan and Enalapril in Patients With Heart Failure
Official title: A Multi-center, Prospective, Randomized, Double-blind Study to Assess the Impact of Sacubitril/Valsartan vs. Enalapril on Daily Physical Activity Using a Wrist Worn Actigraphy Device in Adult Chronic Heart Failure Patients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Chronic Heart Failure With Reduced Ejection Fraction
Keywords: sacubitril/valsartan
enalapril
physical activity
actigraphy
sleep
heart failure
reduced ejection fraction
randomized controlled trial
accelerometry
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2016-09-14
Enrollment: 621
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).


Eligibility criteria: Key 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.

Key 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.

Primary outcomes:
measure: Change From Baseline (Week 0) in the Six Minute Walk Test (6MWT) at End of Study (Week 12)
timeFrame: Baseline, Week 12
measure: Change From Baseline (Week 0) in Mean Daily Non-sedentary Daytime Activity at End of Study (Week 12)
timeFrame: Baseline, Week 12
Secondary outcomes:
measure: Number and Percentage of Participants With Improved Performance (>= 30 m) in the Six Minute Walk Test (6MWT) - FAS
timeFrame: Baseline, Week 12
measure: Number and Percentage of Participants With Improved Performance (>= 30 m) in the Six Minute Walk Test (6MWT) - FAS Subset Without AE/SAE
timeFrame: Baseline, Week 12
measure: Number and Percentage of Participants With Improved Performance (>= 30 m) in the 6MWT Which Walked Equal to or Less Than 300 Meters at Baseline - FAS
timeFrame: Baseline, Week 12
measure: Number and Percentage of Participants With Improved Performance (>= 30 m) in the 6MWT Which Walked Equal to or Less Than 300 Meters at Baseline - FAS Subset Without AE/SAE
timeFrame: Baseline, Week 12
measure: Number and Percentage of Participants With Improved Performance (>= 30 m) in the 6MWT Which Walked 100-450 Meters at Baseline - FAS
timeFrame: Baseline, Week 12
measure: Number and Percentage of Participants With Improved Performance (>= 30 m) in the 6MWT Which Walked 100-450 Meters at Baseline - FAS Subset Without AE/SAE
timeFrame: Baseline, Week 12
measure: Change From Baseline (Week 0) in the Six Minute Walk Test (6MWT) at Weeks 4 and 8
timeFrame: Baseline, Week 4 and Week 8
measure: Number and Percentage of Participants Who Show Increased Levels (>= 10% Increase) of Non Sedentary Daytime Physical Activity at Week 12 Compared to Baseline
timeFrame: Baseline, Week 12
measure: Number and Percentage of Participants Achieving PGA Score at Weeks 4, 8 and 12
timeFrame: Week 4, Week 8, Week 12
measure: Number and Percentage of Participants With Improved Symptoms of Heart Failure as Assessed by Patient Global Assessment (PGA)
timeFrame: Week 4, Week 8, Week 12
measure: Change From Baseline in Mean Daily Non-sedentary Daytime Activity in Weekly Intervals
timeFrame: Baseline, Week 1, Week 2, Week 3, Week 4, Week 5, Week 6, Week 7, Week 8, Week 9, Week 10, Week 11 and Week 12
measure: Change From Baseline in Mean Daily Non-sedentary Daytime Activity in Two-weekly Intervals
timeFrame: Baseline, Weeks 0 to 2, Weeks 2 to 4, Weeks 4 to 6, Weeks 6 to 8, Weeks 8 to 10, Weeks 10 to 12
measure: Change From Baseline in Mean Daily Light Non-sedentary Daytime Physical Activity
timeFrame: Baseline, Week 1, Week 2, Week 3, Week 4, Week 5, Week 6, Week 7, Week 8, Week 9, Week 10, Week 11 and Week 12
measure: Change From Baseline in Mean Daily Moderate-to-Vigorous Non-sedentary Daytime Physical Activity
timeFrame: Baseline, Week 1, Week 2, Week 3, Week 4, Week 5, Week 6, Week 7, Week 8, Week 9, Week 10, Week 11 and Week 12
measure: Total Weekly Time Spent in Non-sedentary Daytime Physical Activity
timeFrame: Baseline, Week 1, Week 2, Week 3, Week 4, Week 5, Week 6, Week 7, Week 8, Week 9, Week 10, Week 11 and Week 12
measure: Total Weekly Time Spent in Light Non-sedentary Daytime Physical Activity
timeFrame: Baseline, Week 1, Week 2, Week 3, Week 4, Week 5, Week 6, Week 7, Week 8, Week 9, Week 10, Week 11 and Week 12
measure: Total Weekly Time Spent in Moderate-to-Vigorous Non-sedentary Daytime Physical Activity
timeFrame: Baseline, Week 1, Week 2, Week 3, Week 4, Week 5, Week 6, Week 7, Week 8, Week 9, Week 10, Week 11 and Week 12
measure: Change From Baseline in Peak Six Minutes of Daytime Physical Activity
timeFrame: Baseline, Week 2, Week 4, Week 6, Week 8 and Week 12
Other outcomes:
Locations:
city: Edegem
country: Belgium
facility: Novartis Investigative Site
state: Antwerpen
city: Dendermonde
country: Belgium
facility: Novartis Investigative Site
city: Geel
country: Belgium
facility: Novartis Investigative Site
city: Gent
country: Belgium
facility: Novartis Investigative Site
city: Turnhout
country: Belgium
facility: Novartis Investigative Site
city: Pleven
country: Bulgaria
facility: Novartis Investigative Site
city: Plovdiv
country: Bulgaria
facility: Novartis Investigative Site
city: Sofia
country: Bulgaria
facility: Novartis Investigative Site
city: Sofia
country: Bulgaria
facility: Novartis Investigative Site
city: Sofia
country: Bulgaria
facility: Novartis Investigative Site
city: Brno
country: Czechia
facility: Novartis Investigative Site
state: Czech Republic
city: Chomutov
country: Czechia
facility: Novartis Investigative Site
state: Czech Republic
city: Svitavy
country: Czechia
facility: Novartis Investigative Site
state: Czech Republic
city: Most
country: Czechia
facility: Novartis Investigative Site
state: CZE
city: Kolin
country: Czechia
facility: Novartis Investigative Site
city: Praha 10
country: Czechia
facility: Novartis Investigative Site
city: Praha 5
country: Czechia
facility: Novartis Investigative Site
city: Helsingoer
country: Denmark
facility: Novartis Investigative Site
city: Odense C
country: Denmark
facility: Novartis Investigative Site
city: Randers
country: Denmark
facility: Novartis Investigative Site
city: Roskilde
country: Denmark
facility: Novartis Investigative Site
city: Svendborg
country: Denmark
facility: Novartis Investigative Site
city: Tallinn
country: Estonia
facility: Novartis Investigative Site
city: Tallinn
country: Estonia
facility: Novartis Investigative Site
city: Tartu
country: Estonia
facility: Novartis Investigative Site
city: Hameenlinna
country: Finland
facility: Novartis Investigative Site
city: Tampere
country: Finland
facility: Novartis Investigative Site
city: Auxerre
country: France
facility: Novartis Investigative Site
city: Clermont-Ferrand Cedex 1
country: France
facility: Novartis Investigative Site
city: Metz Tessy
country: France
facility: Novartis Investigative Site
city: Dresden
country: Germany
facility: Novartis Investigative Site
state: Sachsen
city: Bad Homburg
country: Germany
facility: Novartis Investigative Site
city: Berlin
country: Germany
facility: Novartis Investigative Site
city: Berlin
country: Germany
facility: Novartis Investigative Site
city: Berlin
country: Germany
facility: Novartis Investigative Site
city: Berlin
country: Germany
facility: Novartis Investigative Site
city: Buchholz in der Nordheide
country: Germany
facility: Novartis Investigative Site
city: Dietzenbach
country: Germany
facility: Novartis Investigative Site
city: Elsterwerda
country: Germany
facility: Novartis Investigative Site
city: Essen
country: Germany
facility: Novartis Investigative Site
city: Frankfurt
country: Germany
facility: Novartis Investigative Site
city: Halberstadt
country: Germany
facility: Novartis Investigative Site
city: Hamburg
country: Germany
facility: Novartis Investigative Site
city: Hassloch
country: Germany
facility: Novartis Investigative Site
city: Leipzig
country: Germany
facility: Novartis Investigative Site
city: Loehne
country: Germany
facility: Novartis Investigative Site
city: Mannheim
country: Germany
facility: Novartis Investigative Site
city: Muehldorf
country: Germany
facility: Novartis Investigative Site
city: Nuremberg
country: Germany
facility: Novartis Investigative Site
city: Reinfeld
country: Germany
facility: Novartis Investigative Site
city: Schwaebisch Hall
country: Germany
facility: Novartis Investigative Site
city: Siegen
country: Germany
facility: Novartis Investigative Site
city: Wallerfing
country: Germany
facility: Novartis Investigative Site
city: Wedel
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facility: Novartis Investigative Site
city: Wermsdorf
country: Germany
facility: Novartis Investigative Site
city: Alexandroupolis
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facility: Novartis Investigative Site
state: Evros
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facility: Novartis Investigative Site
state: GR
city: Athens
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facility: Novartis Investigative Site
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country: Greece
facility: Novartis Investigative Site
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country: Greece
facility: Novartis Investigative Site
city: Kopavogur
country: Iceland
facility: Novartis Investigative Site
city: Reykjavik
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facility: Novartis Investigative Site
city: Dublin 7
country: Ireland
facility: Novartis Investigative Site
city: Jelgava
country: Latvia
facility: Novartis Investigative Site
city: Ogre
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facility: Novartis Investigative Site
city: Riga
country: Latvia
facility: Novartis Investigative Site
city: Riga
country: Latvia
facility: Novartis Investigative Site
city: Riga
country: Latvia
facility: Novartis Investigative Site
city: Kaunas
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facility: Novartis Investigative Site
state: LTU
city: Klaipeda
country: Lithuania
facility: Novartis Investigative Site
state: LTU
city: Vilnius
country: Lithuania
facility: Novartis Investigative Site
city: Goes
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facility: Novartis Investigative Site
city: Haarlem
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facility: Novartis Investigative Site
city: Heerlen
country: Netherlands
facility: Novartis Investigative Site
city: Leiderdorp
country: Netherlands
facility: Novartis Investigative Site
city: Roermond
country: Netherlands
facility: Novartis Investigative Site
city: Veldhoven
country: Netherlands
facility: Novartis Investigative Site
city: Feiring
country: Norway
facility: Novartis Investigative Site
city: Lodz
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facility: Novartis Investigative Site
state: Lodzkie
city: Warszawa
country: Poland
facility: Novartis Investigative Site
state: Mazowieckie
city: Warszawa
country: Poland
facility: Novartis Investigative Site
city: Warszawa
country: Poland
facility: Novartis Investigative Site
city: Warszawa
country: Poland
facility: Novartis Investigative Site
city: Ferrol
country: Spain
facility: Novartis Investigative Site
state: A Coruna
city: Elche
country: Spain
facility: Novartis Investigative Site
state: Alicante
city: Cordoba
country: Spain
facility: Novartis Investigative Site
state: Andalucia
city: Granada
country: Spain
facility: Novartis Investigative Site
state: Andalucia
city: Huelva
country: Spain
facility: Novartis Investigative Site
state: Andalucia
city: Sanlúcar de Barrameda
country: Spain
facility: Novartis Investigative Site
state: Andalucia
city: Sevilla
country: Spain
facility: Novartis Investigative Site
state: Andalucia
city: Gijon
country: Spain
facility: Novartis Investigative Site
state: Asturias
city: Oviedo
country: Spain
facility: Novartis Investigative Site
state: Asturias
city: Villamartin
country: Spain
facility: Novartis Investigative Site
state: Cadiz
city: Santander
country: Spain
facility: Novartis Investigative Site
state: Cantabria
city: Aranda de Duero
country: Spain
facility: Novartis Investigative Site
state: Castilla Y Leon
city: Burgos
country: Spain
facility: Novartis Investigative Site
state: Castilla Y Leon
city: Leon
country: Spain
facility: Novartis Investigative Site
state: Castilla Y Leon
city: Soria
country: Spain
facility: Novartis Investigative Site
state: Castilla Y Leon
city: Sabadell
country: Spain
facility: Novartis Investigative Site
state: Cataluña
city: Alicante
country: Spain
facility: Novartis Investigative Site
state: Comunidad Valenciana
city: Caceres
country: Spain
facility: Novartis Investigative Site
state: Extremadura
city: Lugo
country: Spain
facility: Novartis Investigative Site
state: Galicia
city: Santiago de Compostela
country: Spain
facility: Novartis Investigative Site
state: Galicia
city: Manises
country: Spain
facility: Novartis Investigative Site
state: Valencia
city: Barcelona
country: Spain
facility: Novartis Investigative Site
city: Girona
country: Spain
facility: Novartis Investigative Site
city: Madrid
country: Spain
facility: Novartis Investigative Site
city: Madrid
country: Spain
facility: Novartis Investigative Site
city: Lund
country: Sweden
facility: Novartis Investigative Site
city: Molndal
country: Sweden
facility: Novartis Investigative Site
city: Stockholm
country: Sweden
facility: Novartis Investigative Site
city: Stockton on Tees
country: United Kingdom
facility: Novartis Investigative Site
state: Cleveland
city: Rothwell
country: United Kingdom
facility: Novartis Investigative Site
state: GBR
city: Faringdon
country: United Kingdom
facility: Novartis Investigative Site
state: Oxfordshire
city: Gateshead
country: United Kingdom
facility: Novartis Investigative Site
state: Tyne And Wear
city: Bournemouth
country: United Kingdom
facility: Novartis Investigative Site
city: Cumbria
country: United Kingdom
facility: Novartis Investigative Site
city: Poole
country: United Kingdom
facility: Novartis Investigative Site
city: Wellingborough
country: United Kingdom
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References: