Clinical trial NCT04916470: Research Study to Look at How Well Semaglutide Works in People Living With Heart Failure, Obesity and Type 2 Diabetes
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, and Type 2 Diabetes
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Heart Failure With Preserved Ejection Fraction (HFpEF) and Diabetes Mellitus, Type 2
Lead sponsor: Novo Nordisk A/S
Sponsor class: INDUSTRY
First posted: 2021-06-07
Enrollment: 617
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 participants' daily life is affected by their heart failure. The study will also look at the change in participants' body weight.

This study will compare the effect of semaglutide (a new medicine) compared to "dummy" medicine on body weight and heart failure symptoms.

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 and physical activity.

The study will last for about 59 weeks, that is a little more than 1 year. Participants will have 12 clinic visits with the study doctor.

* At 6 of the visits participants will have blood samples taken.
* At 5 of the visits participants will be asked to fill in a questionnaire
* At 4 of the visits participants will have to do a 6-minute walking test
* At 3 of the visits participants will have a test to check the heart.
* participants will have their eyes checked before or at the start of the study and at the end of the study

Women cannot take part if 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% at screening
* Diagnosed with T2D greater than or equal to 90 days prior to the day of screening
* HbA1c of below or equal to 10.0% as measured at the screening visit

Exclusion Criteria:

* A self-reported change in body weight greater than 5 kg (11 lbs) within 90 days before screening irrespective of medical records
* Uncontrolled and potentially unstable diabetic retinopathy or maculopathy. Verified by a fundus examination performed within 90 days prior to screening or in the period between screening and randomisation. Pharmacological pupil-dilation is a requirement unless using a digital fundus photography camera specified for non-dilated examination.

Primary outcomes:
measure: Change in KCCQ (Kansas City Cardiomyopathy Questionnaire) clinical summary score
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 6-minute walking distance
timeFrame: From baseline (week 0) to end of treatment (week 52)
measure: Hierarchical composite of time to all-cause death
timeFrame: From baseline (week 0) to end of study (week 57)
measure: Hierarchical composite of number of heart failure events requiring hospitalisation or urgent heart failure visit
timeFrame: From baseline (week 0) to end of study (week 57)
measure: Hierarchical composite of time to first heart failure event requiring hospitalisation or urgent heart failure visit
timeFrame: From baseline (week 0) to end of study (week 57)
measure: Hierarchical composite of difference at least 15 inKansas City Cardiomyopathy Questionnaire (KCCQ) clinical summary score change from baseline to 52 weeks
timeFrame: From baseline (week 0) to end of study (week 57)
measure: Hierarchical composite of difference at least 10 in KCCQ clinical summary score change from baseline to 52 weeks
timeFrame: From baseline (week 0) to end of study (week 57)
measure: Hierarchical composite of difference at least 5 in KCCQ clinical summary score change from baseline to 52 weeks
timeFrame: From baseline (week 0) to end of study (week 57)
measure: Hierarchical composite of difference at least 30 metres in six-minute walking distance change from baseline to 52 weeks (assessed by the win ratio)
timeFrame: From baseline (week 0) to end of study (week 57)
measure: Change in C-Reactive Protein
timeFrame: From baseline (week -2) to end of treatment (week 52)
measure: Participant achieving 10% weight loss or more (Yes/No)
timeFrame: From baseline (week 0) to end of treatment (week 52)
measure: Participant achieving 15% weight loss or more (Yes/No)
timeFrame: From baseline (week 0) to end of treatment (week 52)
measure: Participant achieving 20% weight loss or more (Yes/No)
timeFrame: From baseline (week 0) to end of treatment (week 52)
measure: Participant improving 5 points or more in KCCQ clinical summary score
timeFrame: From baseline (week 0) to end of treatment (week 52)
measure: Participant 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
timeFrame: From baseline (week 0) to end of treatment (week 52)
measure: Participant achieving threshold for clinically meaningful within-subject change in KCCQ-CSS
timeFrame: From baseline (week 0) to end of treatment (week 52)
measure: Participant achieving threshold for clinically meaningful within-subject change in 6MWD
timeFrame: From baseline (week 0) to end of treatment (week 52)
measure: Change in waist circumference
timeFrame: From baseline (week 0) to end of treatment (visit 52)
measure: Change in systolic blood pressure
timeFrame: From baseline (week -2) to end of treatment (week 52)
measure: Change in glycated haemoglobin (HbA1c)
timeFrame: From baseline (week 0) to end of treatment (week 52)
measure: Number of treatment emergent severe or clinically significant hypoglycaemia episodes
timeFrame: From baseline (week 0) to end of trial (week 57)
Other outcomes:
Locations:
city: Fairhope
country: United States
facility: Eastern Shore Rsrch Inst, LLC
state: Alabama
city: Los Angeles
country: United States
facility: Keck Medical Center of USC - Outpatient Clinic
state: California
city: Jacksonville
country: United States
facility: Baptist Heart Specialists_Jacksonville
state: Florida
city: Arlington Heights
country: United States
facility: Northwest Heart Clin. Res.
state: Illinois
city: Hazel Crest
country: United States
facility: Chicago Medical Research LLC
state: Illinois
city: Indianapolis
country: United States
facility: Ascension St. Vincent Medical Group
state: Indiana
city: Topeka
country: United States
facility: Cotton-O'Neil Heart Center
state: Kansas
city: Elizabethtown
country: United States
facility: Baptist Health Woodland
state: Kentucky
city: Louisville
country: United States
facility: Baptist Health Louisville
state: Kentucky
city: Bossier City
country: United States
facility: Grace Research, LLC
state: Louisiana
city: Shreveport
country: United States
facility: Grace Research, LLC_Shreveport
state: Louisiana
city: Baltimore
country: United States
facility: John Hopkins Hospital
state: Maryland
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Jackson
country: United States
facility: Univ of Mississippi Med Ctr
state: Mississippi
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: Lincoln
country: United States
facility: Bryan Heart
state: Nebraska
city: Omaha
country: United States
facility: CHI Health Clinic Cardiology (CUMC - Bergan Mercy)
state: Nebraska
city: Morehead City
country: United States
facility: Carteret Medical Group
state: North Carolina
city: Winston-Salem
country: United States
facility: Wake Forest Baptist Health
state: North Carolina
city: Dallas
country: United States
facility: University of Texas Southwestern Medical Center
state: Texas
city: Richmond
country: United States
facility: Virginia Commonwealth University
state: Virginia
city: Richmond
country: United States
facility: Virginia Commonwealth University
state: Virginia
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: Braunau
country: Austria
facility: Krankenhaus St. Josef Braunau
city: Graz
country: Austria
facility: Medizinische Universität Graz
city: Saint Stefan
country: Austria
facility: Fließer-Görzer [Ordination]
city: Wien
country: Austria
facility: Imed 19- privat
city: Wien
country: Austria
facility: Universitätsklinik für Innere Medizin II
city: Calgary
country: Canada
facility: University of Calgary_Calgary
state: Alberta
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: Terrebonne
country: Canada
facility: Ctr de Med Metab de Lanaudiere
state: Quebec
city: Quebec
country: Canada
facility: Institut universitaire de cardiologie
city: Broumov
country: Czechia
facility: Edumed Broumov
city: Praha 2
country: Czechia
facility: Fakultní poliklinika VFN ambulance Srdecniho selhani
city: Praha 4
country: Czechia
facility: IKEM
city: Praha 7
country: Czechia
facility: Poliklinika Holešovice VISIONARY - MEDICON a.s.
city: Praha 7
country: Czechia
facility: Poliklinika Holešovice VISIONARY - Medicon Pharm s.r.o.
city: Berlin
country: Germany
facility: Charite Universitatsmedizin Berlin KöR
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: Leipzig
country: Germany
facility: University of Leipzig - Kardiologie
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: Debrecen
country: Hungary
facility: DE KK Kardiológiai és Szívsebészeti klinika
city: Miskolc
country: Hungary
facility: Borsod-Abaúj-Zemplén Megyei Központi Kórház
city: Zalaegerszeg
country: Hungary
facility: Zala Megyei Szent Rafael Kórház
city: New Delhi
country: India
facility: G B Pant Institute of Postgraduate Medical Education and Research
state: Delhi
city: New Delhi
country: India
facility: Max Super Speciality Hospital, Saket
state: Delhi
city: Kochi
country: India
facility: Lisie Hospital
state: Kerala
city: Nashik
country: India
facility: Vijan Cardiac & Critical Care
state: Maharashtra
city: Nashik
country: India
facility: Vijan Hospital & Research Centre
state: Maharashtra
city: New Dehli
country: India
facility: VMMC & Safdarjung Hospital
state: New Delhi
city: Bikaner
country: India
facility: SP Medical College & A.G.Hospital Bikaner
state: Rajasthan
city: Bikaner
country: India
facility: SP Medical College
state: Rajasthan
city: Chennai
country: India
facility: Apollo Hospitals Education & Research Foundation
state: Tamil Nadu
city: Lucknow
country: India
facility: Gandhi Memorial Hospital- King George's Medical University
state: Uttar Pradesh
city: New Delhi
country: India
facility: G B Pant Institute of Postgraduate Medical Education and Res
city: New Delhi
country: India
facility: Max Super Speciality Hospital_New Delhi
city: New Delhi
country: India
facility: Sir Ganga Ram Hospital
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: Bergamo
country: Italy
facility: ASST Papa Giovanni XXIII
state: Bg
city: Brescia
country: Italy
facility: Spedali Civili Brescia
state: Bs
city: Cona (Ferrara)
country: Italy
facility: A.O.U. Ferrara, Sant'Anna
state: Fe
city: Milano
country: Italy
facility: Centro Cardiologico Monzino. Istituto di Ricovero e Cura
city: Roma
country: Italy
facility: A.O.U. Policlinico Umberto I
city: Rome
country: Italy
facility: Policlinico A. Gemelli IRCCS
city: Himeji-shi, Hyogo
country: Japan
facility: Hyogo Prefectural HarimaHimeji General Medical Center_Cardiology
city: Kitakyushu-shi,Fukuoka
country: Japan
facility: Kokura Memorial Hospital, Cardiology
city: Omihachiman-shi, Siga
country: Japan
facility: Omihachiman Community Medical Center_Omihachiman-shi, Siga
city: Osaka
country: Japan
facility: Osaka City General Hospital
city: Sapporo-shi, Hokkaido
country: Japan
facility: Hanaoka Seishu Memorial Hospital
city: Tokyo
country: Japan
facility: Tokyo Shinagawa Hospital Social Medical Corporation Association Tokyokyojuno-kai
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 Im Wojskowej Akademii Medycznej Centralny Szpital Weteranow
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: Santiago de Compostela
country: Spain
facility: Complejo Hospitalario Universitario de Santiago
city: Sevilla
country: Spain
facility: Clínica Nuevas Tecnologías en Diabetes y Endocrinología
city: Valencia
country: Spain
facility: Hospital Clínico Universitario de Valencia
city: Göteborg
country: Sweden
facility: Dept of Med Sahlgrenska/Östra
city: Uppsala
country: Sweden
facility: Hjärtmottagningen
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: Kosiborod MN, Abildstrom SZ, Borlaug BA, Butler J, Christensen L, Davies M, Hovingh KG, Kitzman DW, Lindegaard ML, Moller DV, Shah SJ, Treppendahl MB, Verma S, Petrie MC. Design and Baseline Characteristics of STEP-HFpEF Program Evaluating Semaglutide in Patients With Obesity HFpEF Phenotype. JACC Heart Fail. 2023 Aug;11(8 Pt 1):1000-1010. doi: 10.1016/j.jchf.2023.05.010. Epub 2023 May 21.