Research Study to Investigate How Well Semaglutide Works in People Living With Heart Failure and Obesity

Obesity Clinical Trial

— STEP-HFpEF  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04788511
• Other study ID #: EX9536-4665
• Secondary ID: U1111-1243-43582
• Status: Completed
• Phase: Phase 3
• Start date: March 16, 2021
• Est. completion date: April 18, 2023

Study information

• Verified date: June 2024
• Source: Novo Nordisk A/S
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 529
• Est. completion date: April 18, 2023
• Est. primary completion date: April 18, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Heart Failure
• Obesity

Intervention

Drug:
• Semaglutide
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 (semaglutide)
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.

Locations

Country	Name	City	State
Argentina	CEMEDIC	Caba	Buenos Aires
Argentina	CEMEDIC	Caba
Argentina	Centro de Investigación y Prevención Cardiovascular	Caba
Argentina	Centro de Investigación y Prevención Cardiovascular	Caba
Argentina	Cardiología Palermo	Ciudad Autónoma de Buenos Aire
Argentina	Instituto de Cardiología de Corrientes	Corrientes
Argentina	Instituto de Cardiología de Corrientes	Corrientes	Buenos Aires
Argentina	Consultorio Integral de Atención al Diabético	Morón
Argentina	Sanatorio Britanico S.A.	Rosario, Santa Fe
Australia	Flinders Medical Centre	Bedford Park	South Australia
Australia	Concord Repatriation General Hospital - Cardiology	Concord	New South Wales
Australia	The Canberra Hospital_Garran	Garran	Australian Capital Territory
Australia	Geelong Cardiology Research Unit	Geelong	Victoria
Australia	Liverpool Hospital	Liverpool	New South Wales
Canada	Cambridge Cardiac Care Centre	Cambridge	Ontario
Canada	Partnrs Adv Cardio Eval (PACE)	Newmarket	Ontario
Canada	Institut Universitaire de Cardiologie et de Pneumologie. de Quebec - Universite Laval	Quebec
Canada	Heart Health Institute Research, Inc.	Scarborough	Ontario
Czechia	Nemocnice Jihlava Kardiologie	Jihlava
Czechia	Vseobecna fakultni nemocnice a 1 LF UK v Praze	Praha 2
Czechia	IKEM	Praha 4
Czechia	Poliklinika Holešovice VISIONARY - MEDICON a.s.	Praha 7
Czechia	Poliklinika Holešovice VISIONARY - Medicon Pharm s.r.o.	Praha 7
Czechia	Nemocnice Slany Kardiologie	Slany
Czechia	Nemocnice Tábor a.s.	Tábor
Denmark	Aarhus Universitetshospital, Skejby Hjertesygdomme	Aarhus N
Denmark	Herlev og Gentofte Hospital	Hellerup	Region Hovedstaden
Denmark	Kardiologisk Odense & Svendborg	Svendborg
Germany	Charite Universitatsmedizin Berlin KöR	Berlin
Germany	Hausaerztlich-Kardiologisches MVZ Am Felsenkeller GmbH	Dresden
Germany	Zentrum fuer klinische Studien Suedbrandenburg GmbH	Elsterwerda
Germany	MVZ CCB Frankfurt Und Main-Taunus GbR	Frankfurt
Germany	Medical Center - University Of Freiburg	Freiburg
Germany	Appel	Kassel
Germany	Universitatsklinikum Wurzburg AöR	Würzburg
Hungary	Lausmed Kft.	Baja	Bács-Kiskun Vármegye
Hungary	Gottsegen György Országos Kardiológiai Intézet	Budapest
Hungary	Jahn Ferenc Dél-pesti Kórház és Rendelointézet	Budapest
Hungary	Semmelweis Egyetem Szent Rókus Klinikai Tömb	Budapest
Hungary	Semmelweis Egyetem Városmajori Szív- és Érgyógyászat	Budapest
Hungary	Szent Margit Rendelointézet Nonprofit Kft.	Budapest
Hungary	Selye János Kórház	Komárom	Komárom-Esztergom
Hungary	Borsod-Abaúj-Zemplén Megyei Központi Kórház	Miskolc
Hungary	Zala Megyei Szent Rafael Kórház	Zalaegerszeg
Israel	Hadassah Ein Kerem MC - Cardio	Jerusalem
Israel	Cardiology department, Western Galilee Medical Center	Nahariya
Israel	Heart Failure Unit, Rabin Medical Center - Beilinson Campus	Petah-Tikva
Israel	Cardio Vascular Research Center Sourasky MC	Tel Aviv
Israel	Sheba Medica Center - Clinical Research Unit	Tel Hashomer
Netherlands	Gelre Ziekenhuizen Apeldoorn	Apeldoorn
Netherlands	Rode Kruis Ziekenhuis Beverwijk	Beverwijk
Netherlands	UMC Groningen	Groningen
Netherlands	Saxenburgh Medisch Centrum	Hardenberg
Netherlands	Medisch Centrum Leeuwarden	Leeuwarden
Netherlands	Bravis Ziekenhuis	Roosendaal
Poland	Uniwersytecki Szpital Kliniczny w Bialymstoku K. Kardio	Bialystok	Podlaskie
Poland	Malopolskie Centrum Sercowo-Naczyniowe	Chrzanow	Malopolskie
Poland	Ind. Prak. Lek. w dziedz. Kardiologii lek. med. K. Cymerman	Gdynia
Poland	Pro Familia Altera Sp. z o.o.	Katowice	Slaskie
Poland	Uniwersytecki Szpital Kliniczny Im Wojskowej Akademii Medycznej Centralny Szpital Weteranow	Lodz	Lodzkie
Poland	I Katedra i Klinika Kardiologii WUM SPCSK	Warsaw
Spain	Hospital Universitario La Zarzuela	Madrid
Spain	Complejo Hospitalario Universitario de Santiago	Santiago de Compostela
Spain	Hospital Clínico Universitario de Valencia	Valencia
United Kingdom	Southmead Hospital	Bristol
United Kingdom	Ninewells Hospital	Dundee
United Kingdom	Glasgow Clinical Research Facility	Glasgow
United Kingdom	Queen Elizabeth University Hospital	Glasgow
United Kingdom	Wycombe General Hospital	High Wycombe
United Kingdom	University Hospital Aintree	Liverpool
United Kingdom	Manchester Royal Infirmary_Manchester_0	Manchester
United Kingdom	Great Western Hospital	Swindon
United Kingdom	St. Richards Hospital	West Sussex
United States	Northwest Heart Clinical Research, LLC	Arlington Heights	Illinois
United States	John Hopkins Hospital	Baltimore	Maryland
United States	Lindner Center,Christ Hospital	Cincinnati	Ohio
United States	University of Texas Southwestern Medical Center	Dallas	Texas
United States	Northwestern University_Chicago_0	Evanston	Illinois
United States	Eastern Shore Rsrch Inst, LLC	Fairhope	Alabama
United States	St Francis Hospital Lindner Research Center	Greenvale	New York
United States	Heart Clinic of Hammond	Hammond	Louisiana
United States	Chicago Medical Research LLC	Hazel Crest	Illinois
United States	Saint Luke's Hospital of Kansas City	Kansas City	Missouri
United States	University of Kansas Medical Center	Kansas City	Kansas
United States	The Research Group of Lexington LLC	Lexington	Kentucky
United States	Baptist Health Louisville	Louisville	Kentucky
United States	NY Presbyt Hosp-W Cornell Med	New York	New York
United States	Hospital of the University of Pennsylvania	Philadelphia	Pennsylvania
United States	Hospital of University of Pennsylvania	Philadelphia	Pennsylvania
United States	Mayo Clinic Rochester	Rochester	Minnesota
United States	St Louis Heart & Vascular, P.C.	Saint Louis	Missouri
United States	Cotton-O'Neil Heart Center	Topeka	Kansas
United States	Wake Forest School of Medicine	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Novo Nordisk A/S

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Canada,  Czechia,  Denmark,  Germany,  Hungary,  Israel,  Netherlands,  Poland,  Spain,  United Kingdom, 

References & Publications (2)

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. — View 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, — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)
Primary	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	Change in Six-minute Walking Distance (6MWD)	Observed mean change from baseline (week 0) in 6 minutes walking distance (6MWD) test to end of treatment (week 52) is presented. The 6MWD is a common test of functional exercise capacity that assesses the distance a participant can walk in 6 minutes. 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	The Hierarchical Composite Endpoint: Percentage of Wins of Participant Pairs	The hierarchical composite outcome measure from baseline (week 0) to end of study (week 57) consists of the components: time to all-cause death, number of heart failure events requiring hospitalization or urgent heart failure visit, time to first heart failure event requiring hospitalization or urgent heart failure visit, difference at least 15 in KCCQ CSS change from baseline to 52 weeks, difference at least 10 in KCCQ CSS change from baseline to 52 weeks, difference at least 5 in KCCQ CSS change from baseline to 52 weeks and difference at least 30 meters in six-minute walking distance change from baseline to 52 weeks. It was analyzed by the win-ratio approach using all participants pairs across treatment groups. Overall summary of wins in each treatment group is presented. The outcome measure was evaluated based on the data from in-trial period. In-trial period was defined as uninterrupted time interval from date of randomization to date of last contact with trial site.	From baseline (week 0) to end of study (week 57)
Secondary	Change in C-Reactive Protein (CRP): Ratio to Baseline	Change in high sensitivity C-reactive protein measured in ratio of C-reactive protein to baseline (week -2) at 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 -2) to end of treatment (week 52)
Secondary	Percentage of Participants Achieving 10 Percent (%) Weight Loss (Yes/No)	Percentage of participants who achieved 10% weight loss (yes/no) from baseline (week 0) to end of treatment (week 52) is presented. In the reported data, 'Yes' infers percentage of participants who have achieved 10% weight loss whereas 'No' infers percentage of participants who have not achieved 10% weight loss. 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	Percentage of Participants Achieving 15% Weight Loss (Yes/No)	Percentage of participants who achieved 15% weight loss (yes/no) from baseline (week 0) to end of treatment (week 52) is presented. In the reported data, 'Yes' infers percentage of participants who have achieved 15% weight loss whereas 'No' infers percentage of participants who have not achieved 15% weight loss. 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	Percentage of Participants Achieving 20% Weight Loss (Yes/No)	Percentage of participants who achieved 20% weight loss (yes/no) from baseline (week 0) to end of treatment (week 52) is presented. In the reported data, 'Yes' infers percentage of participants who have achieved 20% weight loss whereas 'No' infers percentage of participants who have not achieved 20% weight loss 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	Percentage of Participants Improving 5 Points or More in KCCQ Clinical Summary Score (Yes/No)	Percentage of participants improving 5 points or more in KCCQ-CSS from baseline to end of treatment is presented. The KCCQ is standardized 23-item, self-administered instrument that quantifies heart failure symptoms(frequency, severity, and recent change), physical limitation, quality of life, and social limitation. KCCQ-CSS includes the symptom and physical limitation domains of the KCCQ. Scores are transformed to range of 0-100, in which higher scores reflect better health status. In the reported data, 'Yes' infers percentage of participants who have improved 5 points or more in score whereas 'No' infers percentage of participants who have not improved 5 points or more in score. 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	Percentage of Participants Improving 10 Points or More in KCCQ Clinical Summary Score (Yes/No)	Percentage of participants improving 10 points or more in KCCQ-CSS from baseline to end of treatment is presented. The KCCQ is standardized 23-item, self-administered instrument that quantifies heart failure symptoms(frequency, severity, and recent change), physical limitation, quality of life, and social limitation. KCCQ-CSS includes the symptom and physical limitation domains of the KCCQ. Scores are transformed to range of 0-100, in which higher scores reflect better health status. In reported data, 'Yes' infers percentage of participants who have improved 5 points or more in score whereas 'No' infers percentage of participants who have not improved 10 points or more in score. 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	Change in KCCQ Overall Summary Score (KCCQ-OSS)	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 while KCCQ-OSS includes the symptom, physical limitation, quality of life, and social limitation domains. 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)
Secondary	Percentage of Participants Achieving Threshold for Clinically Meaningful Within-participants Change in KCCQ-CSS (PGI-S)	The patient global impression of status (PGI-S) for KCCQ was used to rate participants' symptoms of heart failure using 4-category ordinal scale (no symptoms, mild, moderate, severe). KCCQ is standardized 23-item, self-administered instrument that quantifies heart failure symptoms (frequency, severity, and recent change), physical limitation, quality of life, and social limitation. OSS and all domains have been independently demonstrated to be valid, reliable, and responsive to clinical change. KCCQ-CSS includes symptom and physical limitation domains of the KCCQ. Scores are transformed to range of 0-100, in which higher scores reflect better health status. Outcome measure was evaluated based on data from in-trial period. In-trial period was defined as uninterrupted time interval from date of randomization to date of last contact with trial site. The threshold was defined as mean change in KCCQ-CSS in those participants with one-category improvement in PGI-S from baseline to week 52.	From baseline (week 0) to end of treatment (week 52)
Secondary	Percentage of Participants Achieving Threshold for Clinically Meaningful Within-participants Change in 6MWD (PGI-S)	Observed mean change from baseline in 6 minutes walking distance (6MWD) test using PGI-S is evaluated for this outcome measure. The 6MWD is a common test of functional exercise capacity that assesses the distance a participant can walk in 6 minutes. 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. The threshold was defined as the mean change in 6MWD in those participants with an one-category improvement in PGI-S from baseline to week 52.	From baseline (week 0) to end of treatment (week 52)
Secondary	Change in Systolic Blood Pressure (SBP)	Observed mean change in systolic blood pressure from baseline (week -2) 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 -2) to end of treatment (week 52)
Secondary	Change in Waist Circumference	Change waist circumference from baseline (week 0) to end of the treatment (visit 52) presented. Waist circumference is defined as the abdominal circumference located midway between the lower rib margin and the iliac crest. Measurement must be obtained in standing position with a non-stretchable measuring tape and to the nearest cm or inch. The tape should touch the skin but not compress soft tissue and twists in the tape should be avoided. The participant should be asked to breathe normally. The same measuring tape should be used throughout the trial. 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 (visit 52)