Clinical trial NCT04788511: Research Study to Investigate How Well Semaglutide Works in People Living With Heart Failure and Obesity
Official title: Effect of Semaglutide 2.4 mg Once Weekly on Function and Symptoms in Subjects With Obesity-related Heart Failure With Preserved Ejection Fraction
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Obesity
Lead sponsor: Novo Nordisk A/S
Sponsor class: INDUSTRY
First posted: 2021-03-09
Enrollment: 529
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study will look at how the participants daily life is affected by their heart failure. The study will also look at the change in participants body weight from the start to the end of the study. This is to compare the effect on heart failure symptoms and on body weight in people taking semaglutide (a new medicine) to people taking "dummy" medicine.

Participants will either get semaglutide or "dummy" medicine - which treatment participants get is decided by chance. Participants will need to take 1 injection once a week. The study medicine is injected with a thin needle in a skin fold in the stomach area, thigh or upper arm.

During the study participants will have talks with the study staff about healthy lifestyle choices including healthy food and physical activity.

The study will last for approximately 59 weeks. Participants will have 11 clinic visits and 1 phone call with the study doctor. Women: Women cannot take part if they are pregnant, breast-feeding or plan to become pregnant during the study period.


Eligibility criteria: Inclusion Criteria:

* Male or female, age above or equal to 18 years at the time of signing informed consent.
* Body mass index (BMI) greater than or equal to 30.0 kg/m\^2
* New York Heart Association (NYHA) Class II-IV
* Left ventricular ejection fraction (LVEF) greater than or equal to 45 percentage at screening

Exclusion Criteria:

* A self-reported change in body weight greater than 5 kg (11 lbs) within 90 days before screening irrespective of medical records
* Haemoglobin A1c (HbA1c) greater than or equal to 6.5 percentage (48 mmol/mol) based on latest available value from medical records, no older than 3 months or if unavailable a local measurement at screening

Primary outcomes:
measure: Change in Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ-CSS)
timeFrame: From baseline (week 0) to end of treatment (week 52)
measure: Change in Body Weight
timeFrame: From baseline (week 0) to end of treatment (week 52)
Secondary outcomes:
measure: Change in Six-minute Walking Distance (6MWD)
timeFrame: From baseline (week 0) to end of treatment (week 52)
measure: The Hierarchical Composite Endpoint: Percentage of Wins of Participant Pairs
timeFrame: From baseline (week 0) to end of study (week 57)
measure: Change in C-Reactive Protein (CRP): Ratio to Baseline
timeFrame: From baseline (week -2) to end of treatment (week 52)
measure: Percentage of Participants Achieving 10 Percent (%) Weight Loss (Yes/No)
timeFrame: From baseline (week 0) to end of treatment (week 52)
measure: Percentage of Participants Achieving 15% Weight Loss (Yes/No)
timeFrame: From baseline (week 0) to end of treatment (week 52)
measure: Percentage of Participants Achieving 20% Weight Loss (Yes/No)
timeFrame: From baseline (week 0) to end of treatment (week 52)
measure: Percentage of Participants Improving 5 Points or More in KCCQ Clinical Summary Score (Yes/No)
timeFrame: From baseline (week 0) to end of treatment (week 52)
measure: Percentage of Participants Improving 10 Points or More in KCCQ Clinical Summary Score (Yes/No)
timeFrame: From baseline (week 0) to end of treatment (week 52)
measure: Change in KCCQ Overall Summary Score (KCCQ-OSS)
timeFrame: From baseline (week 0) to end of treatment (week 52)
measure: Percentage of Participants Achieving Threshold for Clinically Meaningful Within-participants Change in KCCQ-CSS (PGI-S)
timeFrame: From baseline (week 0) to end of treatment (week 52)
measure: Percentage of Participants Achieving Threshold for Clinically Meaningful Within-participants Change in 6MWD (PGI-S)
timeFrame: From baseline (week 0) to end of treatment (week 52)
measure: Change in Systolic Blood Pressure (SBP)
timeFrame: From baseline (week -2) to end of treatment (week 52)
measure: Change in Waist Circumference
timeFrame: From baseline (week 0) to end of treatment (visit 52)
Other outcomes:
Locations:
city: Fairhope
country: United States
facility: Eastern Shore Rsrch Inst, LLC
state: Alabama
city: Arlington Heights
country: United States
facility: Northwest Heart Clin. Res.
state: Illinois
city: Evanston
country: United States
facility: Northwestern University_Chicago_0
state: Illinois
city: Hazel Crest
country: United States
facility: Chicago Medical Research LLC
state: Illinois
city: Kansas City
country: United States
facility: University of Kansas Medical Center
state: Kansas
city: Topeka
country: United States
facility: Cotton-O'Neil Heart Center
state: Kansas
city: Lexington
country: United States
facility: The Research Group of Lexington LLC
state: Kentucky
city: Louisville
country: United States
facility: Baptist Health Louisville
state: Kentucky
city: Hammond
country: United States
facility: Heart Clinic of Hammond
state: Louisiana
city: Baltimore
country: United States
facility: John Hopkins Hospital
state: Maryland
city: Rochester
country: United States
facility: Mayo Clinic Rochester
state: Minnesota
city: Kansas City
country: United States
facility: Saint Luke's Hospital of Kansas City
state: Missouri
city: Saint Louis
country: United States
facility: St Louis Heart & Vascular, P.C.
state: Missouri
city: Greenvale
country: United States
facility: St Francis Hospital Lindner Research Center
state: New York
city: New York
country: United States
facility: NY Presbyt Hosp-W Cornell Med
state: New York
city: Winston-Salem
country: United States
facility: Wake Forest School of Medicine
state: North Carolina
city: Cincinnati
country: United States
facility: Lindner Center,Christ Hospital
state: Ohio
city: Philadelphia
country: United States
facility: Hospital of the University of Pennsylvania
state: Pennsylvania
city: Philadelphia
country: United States
facility: Hospital of University of Pennsylvania
state: Pennsylvania
city: Dallas
country: United States
facility: University of Texas Southwestern Medical Center
state: Texas
city: Caba
country: Argentina
facility: CEMEDIC
state: Buenos Aires
city: Corrientes
country: Argentina
facility: Instituto de Cardiología de Corrientes
state: Buenos Aires
city: Caba
country: Argentina
facility: Centro de Investigación y Prevención Cardiovascular
city: Caba
country: Argentina
facility: Centro de Investigación y Prevención Cardiovascular
city: Caba
country: Argentina
facility: CEMEDIC
city: Ciudad Autónoma de Buenos Aire
country: Argentina
facility: Cardiología Palermo
city: Corrientes
country: Argentina
facility: Instituto de Cardiología de Corrientes
city: Morón
country: Argentina
facility: Consultorio Integral de Atención al Diabético
city: Rosario, Santa Fe
country: Argentina
facility: Sanatorio Britanico S.A.
city: Garran
country: Australia
facility: The Canberra Hospital_Garran
state: Australian Capital Territory
city: Concord
country: Australia
facility: Concord Repatriation General Hospital - Cardiology
state: New South Wales
city: Liverpool
country: Australia
facility: Liverpool Hospital
state: New South Wales
city: Bedford Park
country: Australia
facility: Flinders Medical Centre
state: South Australia
city: Geelong
country: Australia
facility: Geelong Cardiology Research Unit
state: Victoria
city: Cambridge
country: Canada
facility: Cambridge Cardiac Care Centre
state: Ontario
city: Newmarket
country: Canada
facility: Partnrs Adv Cardio Eval (PACE)
state: Ontario
city: Scarborough
country: Canada
facility: Heart Health Institute Research, Inc.
state: Ontario
city: Quebec
country: Canada
facility: Institut Universitaire de Cardiologie et de Pneumologie. de Quebec - Universite Laval
city: Jihlava
country: Czechia
facility: Nemocnice Jihlava Kardiologie
city: Praha 2
country: Czechia
facility: Vseobecna fakultni nemocnice a 1 LF UK v Praze
city: Praha 4
country: Czechia
facility: IKEM
city: Praha 7
country: Czechia
facility: MEDICON a.s.
city: Praha 7
country: Czechia
facility: Poliklinika Holešovice VISIONARY - Medicon Pharm s.r.o.
city: Slany
country: Czechia
facility: Nemocnice Slany Kardiologie
city: Tábor
country: Czechia
facility: Nemocnice Tábor a.s.
city: Hellerup
country: Denmark
facility: Herlev og Gentofte Hospital
state: Region Hovedstaden
city: Aarhus N
country: Denmark
facility: Aarhus Universitetshospital, Hjertesygdomme
city: Svendborg
country: Denmark
facility: Kardiologisk Odense & Svendborg
city: Berlin
country: Germany
facility: Charité - Campus Virchow-Klinikum - Kardiologie, Angiologie und Intensivmedizin (CRU)
city: Dresden
country: Germany
facility: MVZ "Am Felsenkeller" (Dresden)
city: Elsterwerda
country: Germany
facility: Zentrum fuer klinische Studien Suedbrandenburg GmbH
city: Frankfurt
country: Germany
facility: MVZ CCB Frankfurt Und Main-Taunus GbR
city: Freiburg
country: Germany
facility: Medical Center - University Of Freiburg
city: Kassel
country: Germany
facility: Appel
city: Würzburg
country: Germany
facility: Universitatsklinikum Würzburg - Zentrum für Herzinsuffizienz
city: Baja
country: Hungary
facility: Lausmed Kft.
state: Bács-Kiskun Vármegye
city: Komárom
country: Hungary
facility: Selye János Kórház
state: Komárom-Esztergom
city: Budapest
country: Hungary
facility: Szent Margit Rendelőintézet Nonprofit Kft.
city: Budapest
country: Hungary
facility: Semmelweis Egyetem Szent Rókus Klinikai Tömb
city: Budapest
country: Hungary
facility: Gottsegen György Országos Kardiológiai Intézet
city: Budapest
country: Hungary
facility: Semmelweis Egyetem Városmajori Szív- és Érgyógyászat
city: Budapest
country: Hungary
facility: Jahn Ferenc Dél-pesti Kórház és Rendelőintézet
city: Miskolc
country: Hungary
facility: Borsod-Abaúj-Zemplén Megyei Központi Kórház
city: Zalaegerszeg
country: Hungary
facility: Zala Megyei Szent Rafael Kórház
city: Jerusalem
country: Israel
facility: Hadassah Ein Kerem MC - Cardio
city: Nahariya
country: Israel
facility: Cardiology department, Western Galilee Medical Center
city: Petah-Tikva
country: Israel
facility: Heart Failure Unit, Rabin Medical Center - Beilinson Campus
city: Tel Aviv
country: Israel
facility: Cardio Vascular Research Center Sourasky MC
city: Tel Hashomer
country: Israel
facility: Sheba Medica Center - Clinical Research Unit
city: Apeldoorn
country: Netherlands
facility: Gelre Ziekenhuizen Apeldoorn
city: Beverwijk
country: Netherlands
facility: Rode Kruis Ziekenhuis Beverwijk
city: Groningen
country: Netherlands
facility: UMC Groningen
city: Hardenberg
country: Netherlands
facility: Saxenburgh Medisch Centrum
city: Leeuwarden
country: Netherlands
facility: Medisch Centrum Leeuwarden
city: Roosendaal
country: Netherlands
facility: Bravis Ziekenhuis
city: Lodz
country: Poland
facility: Uniwersytecki Szpital Kliniczny nr 2 Uniwersytetu Medycznego w Łodzi
state: Lodzkie
city: Chrzanow
country: Poland
facility: Malopolskie Centrum Sercowo-Naczyniowe
state: Malopolskie
city: Bialystok
country: Poland
facility: Uniwersytecki Szpital Kliniczny w Bialymstoku K. Kardio
state: Podlaskie
city: Gdynia
country: Poland
facility: Ind. Prak. Lek. w dziedz. Kardiologii lek. med. K. Cymerman
city: Warsaw
country: Poland
facility: I Katedra i Klinika Kardiologii WUM SPCSK
city: Katowice
country: Poland
facility: Pro Familia Altera Sp. z o.o.
state: Śląskie
city: Madrid
country: Spain
facility: Hospital Universitario La Zarzuela
city: Santiago de Compostela
country: Spain
facility: Complejo Hospitalario Universitario de Santiago
city: Valencia
country: Spain
facility: Hospital Clínico Universitario de Valencia
city: Chichester
country: United Kingdom
facility: St. Richards Hospital
state: West Sussex
city: Bristol
country: United Kingdom
facility: Southmead Hospital
city: Dundee
country: United Kingdom
facility: Ninewells Hospital
city: Glasgow
country: United Kingdom
facility: Glasgow Clinical Research Facility
city: Glasgow
country: United Kingdom
facility: Queen Elizabeth University Hospital
city: High Wycombe
country: United Kingdom
facility: Wycombe General Hospital
city: Liverpool
country: United Kingdom
facility: University Hospital Aintree
city: Manchester
country: United Kingdom
facility: Manchester Royal Infirmary_Manchester_0
city: Swindon
country: United Kingdom
facility: Great Western Hospital
Study officials:
affiliation: Novo Nordisk A/S
name: Clinical Transparency (dept. 1452)
role: STUDY_DIRECTOR
References:
citation: Borlaug BA, Kitzman DW, Davies MJ, Rasmussen S, Barros E, Butler J, Einfeldt MN, Hovingh GK, Moller DV, Petrie MC, Shah SJ, Verma S, Abhayaratna W, Ahmed FZ, Chopra V, Ezekowitz J, Fu M, Ito H, Lelonek M, Melenovsky V, Nunez J, Perna E, Schou M, Senni M, van der Meer P, Von Lewinski D, Wolf D, Kosiborod MN. Semaglutide in HFpEF across obesity class and by body weight reduction: a prespecified analysis of the STEP-HFpEF trial. Nat Med. 2023 Sep;29(9):2358-2365. doi: 10.1038/s41591-023-02526-x. Epub 2023 Aug 27.
citation: Kosiborod MN, Abildstrom SZ, Borlaug BA, Butler J, Rasmussen S, Davies M, Hovingh GK, Kitzman DW, Lindegaard ML, Moller DV, Shah SJ, Treppendahl MB, Verma S, Abhayaratna W, Ahmed FZ, Chopra V, Ezekowitz J, Fu M, Ito H, Lelonek M, Melenovsky V, Merkely B, Nunez J, Perna E, Schou M, Senni M, Sharma K, Van der Meer P, von Lewinski D, Wolf D, Petrie MC; STEP-HFpEF Trial Committees and Investigators. Semaglutide in Patients with Heart Failure with Preserved Ejection Fraction and Obesity. N Engl J Med. 2023 Sep 21;389(12):1069-1084. doi: 10.1056/NEJMoa2306963. Epub 2023 Aug 25.