Research Study to Investigate How Well Semaglutide Works in People Living With Heart Failure and Obesity
STEP-HFpEF
Effect of Semaglutide 2.4 mg Once Weekly on Function and Symptoms in Subjects With Obesity-related Heart Failure With Preserved Ejection Fraction
3 other identifiers
interventional
529
13 countries
146
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_3 obesity
Started Mar 2021
146 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
March 5, 2021
CompletedFirst Posted
Study publicly available on registry
March 9, 2021
CompletedStudy Start
First participant enrolled
March 16, 2021
CompletedPrimary Completion
Last participant's last visit for primary outcome
April 18, 2023
CompletedStudy Completion
Last participant's last visit for all outcomes
April 18, 2023
CompletedResults Posted
Study results publicly available
June 11, 2024
CompletedDecember 5, 2025
November 1, 2025
2.1 years
March 5, 2021
April 18, 2024
November 30, 2025
Conditions
Outcome Measures
Primary Outcomes (2)
Change in Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ-CSS)
The KCCQ is a standardized 23-item, self-administered instrument that quantifies heart failure symptoms (frequency, severity, and recent change), physical limitation, quality of life, and social limitation. The overall summary score and all domains have been independently demonstrated to be valid, reliable, and responsive to clinical change. KCCQ-CSS includes the symptom and physical limitation domains of the KCCQ. Scores are transformed to a range of 0-100, in which higher scores reflect better health status. The outcome measure was evaluated based on the data from in-trial period. In-trial period was defined as the uninterrupted time interval from date of randomization to date of last contact with trial site.
From baseline (week 0) to end of treatment (week 52)
Change in Body Weight
Change in body weight from baseline (week 0) to end of treatment (week 52) is presented. The outcome measure was evaluated based on the data from in-trial period. In-trial period was defined as the uninterrupted time interval from date of randomization to date of last contact with trial site.
From baseline (week 0) to end of treatment (week 52)
Secondary Outcomes (13)
Change in Six-minute Walking Distance (6MWD)
From baseline (week 0) to end of treatment (week 52)
The Hierarchical Composite Endpoint: Percentage of Wins of Participant Pairs
From baseline (week 0) to end of study (week 57)
Change in C-Reactive Protein (CRP): Ratio to Baseline
From baseline (week -2) to end of treatment (week 52)
Percentage of Participants Achieving 10 Percent (%) Weight Loss (Yes/No)
From baseline (week 0) to end of treatment (week 52)
Percentage of Participants Achieving 15% Weight Loss (Yes/No)
From baseline (week 0) to end of treatment (week 52)
- +8 more secondary outcomes
Study Arms (2)
Semaglutide
EXPERIMENTALAll participants will receive either semaglutide 2.4 mg once weekly or placebo once weekly as add-on to standard of care. During the first 16 weeks, the dose of semaglutide or placebo will be gradually escalated from 0.25 mg once weekly until target dose.
Placebo (semaglutide)
PLACEBO COMPARATORAll participants will receive either semaglutide 2.4 mg once weekly or placebo once weekly as add-on to standard of care. During the first 16 weeks, the dose of semaglutide or placebo will be gradually escalated from 0.25 mg once weekly until target dose.
Interventions
Semaglutide will be injected into a skin fold, in the stomach, thigh or upper arm once a week at the same day of the week (to the extent possible) throughout the trial. Dose gradually escalated from 0.25 mg until target dose. The study will last for approximately 59 weeks.
Placebo will be injected into a skin fold, in the stomach, thigh or upper arm once a week at the same day of the week (to the extent possible) throughout the trial. The study will last for approximately 59 weeks.
Eligibility Criteria
You may qualify if:
- 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
You may not qualify if:
- 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
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Novo Nordisk A/Slead
Study Sites (146)
Eastern Shore Rsrch Inst, LLC
Fairhope, Alabama, 36532, United States
National Heart Institute Cal
Beverly Hills, California, 90211, United States
Keck Medical Center of USC - Outpatient Clinic
Los Angeles, California, 90033, United States
Lundquist Inst-Biomed Innovtn
Torrance, California, 90502, United States
Jacksonville Ctr For Clin Res
Jacksonville, Florida, 32216, United States
First Coast Cardiovascular Institute
Jacksonville, Florida, 32257, United States
Baptist Heart Specialists_Jacksonville
Jacksonville, Florida, 32258, United States
CV Res Ctr of S Florida
Miami, Florida, 33173, United States
Endeavor Health Clinical Operations-NCH
Arlington Heights, Illinois, 60005, United States
University of Chicago Medicine
Chicago, Illinois, 60637, United States
Endeavor Health Glenbook Hosp
Evanston, Illinois, 60201, United States
Northwestern University_Chicago_0
Evanston, Illinois, 60208, United States
Chicago Medical Research LLC
Hazel Crest, Illinois, 60429, United States
Ascension St. Vincent Medical Group
Indianapolis, Indiana, 46260, United States
University of Iowa
Iowa City, Iowa, 52242, United States
University of Kansas Medical Center_Kansas City
Kansas City, Kansas, 66160, United States
Cotton-O'Neil Heart Center
Topeka, Kansas, 66606, United States
The Research Group of Lexington LLC
Lexington, Kentucky, 40503, United States
Baptist Health Louisville
Louisville, Kentucky, 40207, United States
Baptist Health Madisonville, Inc
Madisonville, Kentucky, 42431, United States
Grace Research, LLC
Bossier City, Louisiana, 71111, United States
Heart Clinic of Hammond
Hammond, Louisiana, 70403, United States
Grace Research, LLC_Shreveport
Shreveport, Louisiana, 71105, United States
Louisiana Heart Center_Slidell
Slidell, Louisiana, 70458, United States
Louisiana Heart Center
Slidell, Louisiana, 70458, United States
Ascension Saint Agnes Heart Ca
Baltimore, Maryland, 21229, United States
John Hopkins Hospital
Baltimore, Maryland, 21287, United States
Henry Ford Hospital
Detroit, Michigan, 48202-2689, United States
Mayo Clinic Rochester
Rochester, Minnesota, 55902, United States
Univ of Mississippi Med Ctr
Jackson, Mississippi, 39216, United States
Saint Luke's Hospital of Kansas City
Kansas City, Missouri, 64111, United States
St Louis Heart & Vascular, P.C.
St Louis, Missouri, 63136, United States
Bryan Heart
Lincoln, Nebraska, 68506, United States
CHI Health Clinic Cardiology (CUMC - Bergan Mercy)
Omaha, Nebraska, 68124, United States
St Francis Hospital Lindner Research Center
Greenvale, New York, 11548, United States
NY Presbyt Hosp-W Cornell Med
New York, New York, 10021, United States
Rochester General Hospital
Rochester, New York, 14621, United States
Wake Forest School of Medicine
Winston-Salem, North Carolina, 27157, United States
Lindner Center,Christ Hospital
Cincinnati, Ohio, 45219, United States
Abington Memorial Hospital
Abington, Pennsylvania, 19001, United States
Hospital of the University of Pennsylvania
Philadelphia, Pennsylvania, 19104, United States
Hospital of University of Pennsylvania
Philadelphia, Pennsylvania, 19104, United States
Medical Univ of South Carolina_Charleston_0
Charleston, South Carolina, 29425, United States
Sanford Health_Sioux Falls
Sioux Falls, South Dakota, 57117, United States
University of Texas Southwestern Medical Center
Dallas, Texas, 75390, United States
University of Utah School of Medicine
Salt Lake City, Utah, 84132, United States
Cardiology Consultants of Danville Inc.
Danville, Virginia, 24541, United States
Virginia Heart
Falls Church, Virginia, 22042, United States
Sentara Health Research Center
Norfolk, Virginia, 23507, United States
Virginia Commonwealth University Health System
Richmond, Virginia, 23298-5058, United States
CEMEDIC
CABA, Buenos Aires, C1440CFD, Argentina
Master Centre for Argentina
San Carlos de Bolívar, Buenos Aires, 1334, Argentina
Centro de Investigación y Prevención Cardiovascular
CABA, C1061AAS., Argentina
Centro de Investigación y Prevención Cardiovascular
CABA, C1119ACN, Argentina
CEMEDIC
CABA, C1440CFD, Argentina
Cardiología Palermo Duplicate
Ciudad Autónoma de Buenos Aire, 1425, Argentina
Cardiología Palermo
Ciudad Autónoma de Buenos Aire, 1425, Argentina
Instituto de Cardiología de Corrientes
Corrientes, W3400AMZ, Argentina
Consultorio Integral de Atención al Diabético
Morón, B1708IFF, Argentina
Sanatorio Britanico S.A.
Rosario, Santa Fe, S2000CVB, Argentina
The Canberra Hospital_Garran
Garran, Australian Capital Territory, 2605, Australia
Concord Repatriation General Hospital - Cardiology Department
Concord, New South Wales, 2139, Australia
Liverpool Hospital
Liverpool, New South Wales, 2170, Australia
Royal Brisbane Hospital
Herston, Queensland, 4029, Australia
Flinders Medical Centre
Bedford Park, South Australia, 5042, Australia
Geelong Cardiology Research Unit
Geelong, Victoria, 3220, Australia
University of Calgary_Calgary
Calgary, Alberta, T2N 4Z6, Canada
Univ of Alberta Hosp Edmonton
Edmonton, Alberta, T6G 2B7, Canada
North Shore Heart Centre
North Vancouver, British Columbia, V7M 2H4, Canada
SMH Cardiology Clinical Trials Inc.
Surrey, British Columbia, V3V 0C6, Canada
St. Boniface Hospital
Winnipeg, Manitoba, R2H 2HA6, Canada
Cambridge Cardiac Care Centre
Cambridge, Ontario, N1R 6V6, Canada
Partnrs Adv Cardio Eval (PACE)
Newmarket, Ontario, L3Y 2P6, Canada
North York Diagn & Cardiac Ctr
North York, Ontario, M6B 3H7, Canada
Oakville Cardiovascular Research LP
Oakville, Ontario, L6K 3W7, Canada
Dr James Cha
Oshawa, Ontario, L1J 2K1, Canada
Heart Health Institute Research, Inc.
Scarborough Village, Ontario, M1B 4Z8, Canada
Dr. Louis Yao
Weston, Ontario, M9N 1W4, Canada
Clinique Sante Cardio MC
Montreal, Quebec, H1T 3Y7, Canada
Unv de Cardiologie et dePneum
Québec, G1V 4G5, Canada
Nemocnice Jihlava Kardiologie
Jihlava, 586 33, Czechia
Nemocnice Jihlava
Jihlava, 586 33, Czechia
Vseobecna fakultni nemocnice a 1 LF UK v Praze
Prague, 128 00, Czechia
Všeobecná fakultní nemocnice v Praze
Prague, 128 00, Czechia
IKEM
Prague, 140 21, Czechia
MEDICON a.s.
Prague, 170 00, Czechia
Poliklinika Holešovice VISIONARY - Medicon Pharm s.r.o.
Prague, 170 00, Czechia
Nemocnice Slany Kardiologie
Slaný, 274 01, Czechia
Nemocnice Tábor a.s.
Tábor, 390 03, Czechia
Herlev og Gentofte Hospital
Hellerup, Capital Region, 2900, Denmark
Aarhus Universitetshospital, Hjertesygdomme
Aarhus N, 8200, Denmark
Kardiologisk Odense & Svendborg
Svendborg, 5700, Denmark
Charité - Campus Virchow-Klinikum - Kardiologie, Angiologie und Intensivmedizin (CRU)
Berlin, 13353, Germany
Cardiologicum Dresden und Pirna - MVZ "Am Felsenkeller" (Dresden)
Dresden, 01277, Germany
Zentrum fuer klinische Studien Suedbrandenburg GmbH
Elsterwerda, 04910, Germany
MVZ CCB Frankfurt und Main-Taunus GbR
Frankfurt, 60389, Germany
Medical Center - University Of Freiburg
Freiburg im Breisgau, 79106, Germany
Universitätsklinikum Freiburg - Medical Center
Freiburg im Breisgau, 79106, Germany
Appel
Kassel, 34121, Germany
B. Braun Ambulantes Herzzentrum Kassel MVZ GmbH
Kassel, 34121, Germany
Universitatsklinikum Würzburg - Zentrum für Herzinsuffizienz
Würzburg, 97078, Germany
Lausmed Kft.
Baja, Bács-Kiskun county, 6500, Hungary
Selye János Kórház
Komárom, Komárom-Esztergom, 2921, Hungary
Szent Margit Rendelőintézet Nonprofit Kft.
Budapest, 1032, Hungary
Semmelweis Egyetem Szent Rókus Klinikai Tömb
Budapest, 1085, Hungary
Gottsegen György Országos Kardiológiai Intézet
Budapest, 1096, Hungary
Semmelweis Egyetem Városmajori Szív- és Érgyógyászat
Budapest, 1122, Hungary
Jahn Ferenc Dél-pesti Kórház és Rendelőintézet
Budapest, 1204, Hungary
Borsod-Abaúj-Zemplén Megyei Központi Kórház
Miskolc, 3526, Hungary
Zala Megyei Szent Rafael Kórház
Zalaegerszeg, 8900, Hungary
Hadassah Ein Karam MC - Cardio Department
Jerusalem, 91120, Israel
Western Galilee MC - Cardiology Department
Nahariya, 22100, Israel
Rabin MC Beilinson - Heart Failure Unit
Petah Tikva, 49100, Israel
Sourasky MC - Cardio Vascular Research Center
Tel Aviv, 6423906, Israel
Sheba MC - Cardiology Clinical Research Unit
Tel Litwinsky, 5265601, Israel
Gelre Ziekenhuizen Apeldoorn
Apeldoorn, 7334 DZ, Netherlands
Rode Kruis Ziekenhuis Beverwijk
Beverwijk, 1942 LE, Netherlands
UMC Groningen
Groningen, 9713 GZ, Netherlands
Saxenburgh Medisch Centrum
Hardenberg, 7772 SE, Netherlands
Frisius MC Leeuwarden
Leeuwarden, 8934 AD, Netherlands
Bravis Ziekenhuis
Roosendaal, 4708 AE, Netherlands
Malopolskie Centrum Sercowo-Naczyniowe
Chrzanów, Lesser Poland Voivodeship, 32-500, Poland
Uniwersytecki Szpital Kliniczny w Bialymstoku K. Kardio
Bialystok, Podlaskie Voivodeship, 15-540, Poland
Ind. Prak. Lek. w dziedz. Kardiologii lek. med. K. Cymerman
Gdynia, Pomeranian Voivodeship, 81-157, Poland
Pro Familia Altera Sp. z o.o.
Katowice, Silesian Voivodeship, 40-648, Poland
I Katedra i Klinika Kardiologii WUM SPCSK
Warsaw, 02-097, Poland
Uniwersytecki Szpital Kliniczny nr 2 Uniwersytetu Medycznego w Łodzi
Lodz, Łódź Voivodeship, 90-549, Poland
Hospital Universitario La Zarzuela
Madrid, 28023, Spain
Complejo Hospitalario Universitario de Santiago
Santiago de Compostela, 15706, Spain
Hospital Clinico Universitario de Valencia
Valencia, 46010, Spain
Yeovil District Hospital - Clinical Research Unit
Yeovil, Somerset, BA21 4AT, United Kingdom
St. Richards Hospital_Cardiology
Chichester, West Sussex, PO19 6SE, United Kingdom
Barnet Hospital - Cardiology Department
Barnet, EN5 3DJ, United Kingdom
Southmead Hospital
Bristol, BS10 5NB, United Kingdom
Ninewells Hospital
Dundee, DD1 9SY, United Kingdom
Glasgow Clinical Research Facility
Glasgow, G31 2ER, United Kingdom
Glasgow Royal Infirmary
Glasgow, G31 2ER, United Kingdom
Queen Elizabeth University Hospital
Glasgow, G51 4TF, United Kingdom
Wycombe General Hospital
High Wycombe, HP11 2TT, United Kingdom
Aintree University Hospital
Liverpool, L9 7AL, United Kingdom
University Hospital Aintree
Liverpool, L9 7AL, United Kingdom
Manchester Royal Infirmary
Manchester, M13 9WL, United Kingdom
Wythenshawe Hospital_North West Heart Centre
Manchester, M23 9LT, United Kingdom
Great Western Hospital
Swindon, SN3 6BB, United Kingdom
Musgrove Park Hospital
Taunton, TA1 5DA, United Kingdom
St George's Hospital
Tooting, SW17 0QT, United Kingdom
Related Publications (7)
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.
PMID: 37635157BACKGROUNDKosiborod 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.
PMID: 37622681RESULTKosiborod MN, Deanfield J, Pratley R, Borlaug BA, Butler J, Davies MJ, Emerson SS, Kahn SE, Kitzman DW, Lingvay I, Mahaffey KW, Petrie MC, Plutzky J, Rasmussen S, Ronnback C, Shah SJ, Verma S, Weeke PE, Lincoff AM; SELECT, FLOW, STEP-HFpEF, and STEP-HFpEF DM Trial Committees and Investigators. Semaglutide versus placebo in patients with heart failure and mildly reduced or preserved ejection fraction: a pooled analysis of the SELECT, FLOW, STEP-HFpEF, and STEP-HFpEF DM randomised trials. Lancet. 2024 Sep 7;404(10456):949-961. doi: 10.1016/S0140-6736(24)01643-X. Epub 2024 Aug 30.
PMID: 39222642DERIVEDShah SJ, Sharma K, Borlaug BA, Butler J, Davies M, Kitzman DW, Petrie MC, Verma S, Patel S, Chinnakondepalli KM, Einfeldt MN, Jensen TJ, Rasmussen S, Asleh R, Ben-Gal T, Kosiborod MN. Semaglutide and diuretic use in obesity-related heart failure with preserved ejection fraction: a pooled analysis of the STEP-HFpEF and STEP-HFpEF-DM trials. Eur Heart J. 2024 Sep 14;45(35):3254-3269. doi: 10.1093/eurheartj/ehae322.
PMID: 38739118DERIVEDButler J, Shah SJ, Petrie MC, Borlaug BA, Abildstrom SZ, Davies MJ, Hovingh GK, Kitzman DW, Moller DV, Verma S, Einfeldt MN, Lindegaard ML, Rasmussen S, Abhayaratna W, Ahmed FZ, Ben-Gal T, Chopra V, Ezekowitz JA, 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, Kosiborod MN; STEP-HFpEF Trial Committees and Investigators. Semaglutide versus placebo in people with obesity-related heart failure with preserved ejection fraction: a pooled analysis of the STEP-HFpEF and STEP-HFpEF DM randomised trials. Lancet. 2024 Apr 27;403(10437):1635-1648. doi: 10.1016/S0140-6736(24)00469-0. Epub 2024 Apr 7.
PMID: 38599221DERIVEDButler J, Abildstrom SZ, Borlaug BA, Davies MJ, Kitzman DW, Petrie MC, Shah SJ, Verma S, Abhayaratna WP, Chopra V, Ezekowitz JA, Fu M, Ito H, Lelonek M, Nunez J, Perna E, Schou M, Senni M, van der Meer P, von Lewinski D, Wolf D, Altschul RL, Rasmussen S, Kosiborod MN. Semaglutide in Patients With Obesity and Heart Failure Across Mildly Reduced or Preserved Ejection Fraction. J Am Coll Cardiol. 2023 Nov 28;82(22):2087-2096. doi: 10.1016/j.jacc.2023.09.811. Epub 2023 Oct 8.
PMID: 37993201DERIVEDKosiborod MN, Verma S, Borlaug BA, Butler J, Davies MJ, Jon Jensen T, Rasmussen S, Erlang Marstrand P, Petrie MC, Shah SJ, Ito H, Schou M, Melenovsky V, Abhayaratna W, Kitzman DW; STEP-HFpEF Trial Committees and Investigators. Effects of Semaglutide on Symptoms, Function, and Quality of Life in Patients With Heart Failure With Preserved Ejection Fraction and Obesity: A Prespecified Analysis of the STEP-HFpEF Trial. Circulation. 2024 Jan 16;149(3):204-216. doi: 10.1161/CIRCULATIONAHA.123.067505. Epub 2023 Nov 12.
PMID: 37952180DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Results Point of Contact
- Title
- Clinical Reporting Office (2834)
- Organization
- Novo Nordisk A/S
Study Officials
- STUDY DIRECTOR
Clinical Transparency (dept. 1452)
Novo Nordisk A/S
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- DOUBLE
- Who Masked
- PARTICIPANT, INVESTIGATOR
- Masking Details
- Sponsor staff involved in the clinical trial is masked according to company standard procedures.
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
March 5, 2021
First Posted
March 9, 2021
Study Start
March 16, 2021
Primary Completion
April 18, 2023
Study Completion
April 18, 2023
Last Updated
December 5, 2025
Results First Posted
June 11, 2024
Record last verified: 2025-11
Data Sharing
- IPD Sharing
- Will share
According to the Novo Nordisk disclosure commitment on novonordisk-trials.com