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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT04788511




Registration number
NCT04788511
Ethics application status
Date submitted
5/03/2021
Date registered
9/03/2021
Date last updated
11/09/2023

Titles & IDs
Public title
Research Study to Investigate How Well Semaglutide Works in People Living With Heart Failure and Obesity
Scientific title
Effect of Semaglutide 2.4 mg Once Weekly on Function and Symptoms in Subjects With Obesity-related Heart Failure With Preserved Ejection Fraction
Secondary ID [1] 0 0
U1111-1243-4358
Secondary ID [2] 0 0
EX9536-4665
Universal Trial Number (UTN)
Trial acronym
STEP-HFpEF
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Obesity 0 0
Condition category
Condition code
Cardiovascular 0 0 0 0
Coronary heart disease
Cardiovascular 0 0 0 0
Other cardiovascular diseases
Diet and Nutrition 0 0 0 0
Obesity
Metabolic and Endocrine 0 0 0 0
Other metabolic disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Semaglutide
Treatment: Drugs - Placebo (semaglutide)

Experimental: Semaglutide - All 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 Comparator: Placebo (semaglutide) - All 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.


Treatment: Drugs: 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.

Treatment: Drugs: 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.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Change in KCCQ (Kansas City Cardiomyopathy Questionnaire ) clinical summary score
Timepoint [1] 0 0
From baseline (week 0) to end of treatment (week 52)
Primary outcome [2] 0 0
Change in body weight
Timepoint [2] 0 0
From baseline (week 0) to end of treatment (week 52)
Secondary outcome [1] 0 0
Change in six-minute walking distance
Timepoint [1] 0 0
From baseline (week 0) to end of treatment (week 52
Secondary outcome [2] 0 0
Hierarchical composite of time to all-cause death
Timepoint [2] 0 0
From baseline (week 0) to end of study (week 57)
Secondary outcome [3] 0 0
Hierarchical composite of number of heart failure events requiring hospitalisation or urgent heart failure visit
Timepoint [3] 0 0
From baseline (week 0) to end of study (week 57)
Secondary outcome [4] 0 0
Hierarchial composite of time to first heart failure event requiring hospitalisation or urgent heart failure visit
Timepoint [4] 0 0
From baseline (week 0) to end of study (week 57)
Secondary outcome [5] 0 0
Hierarchial composite of difference at least 15 in KCCQ clinical summary score change from baseline to 52 weeks
Timepoint [5] 0 0
From baseline (week 0) to end of study (week 57)
Secondary outcome [6] 0 0
Hierarchical composite of difference at least 10 in KCCQ clinical summary score change from baseline to 52 weeks
Timepoint [6] 0 0
From baseline (week 0) to end of study (week 57)
Secondary outcome [7] 0 0
Hierarchical composite of difference at least 5 in KCCQ clinical summary score change from baseline to 52 weeks
Timepoint [7] 0 0
From baseline (week 0) to end of study (week 57)
Secondary outcome [8] 0 0
Hierarchical composite of difference at least 30 metres in six minute walking distance change from baseline to 52 weeks (assessed by the win ratio)
Timepoint [8] 0 0
From baseline (week 0) to end of study (week 57)
Secondary outcome [9] 0 0
Change in C-Reactive Protein (CRP)
Timepoint [9] 0 0
From baseline (week -2) to end of treatment (week 52)
Secondary outcome [10] 0 0
Subject achieving 10 percentage weight loss or more (Yes/No)
Timepoint [10] 0 0
From baseline (week 0) to end of treatment (week 52)
Secondary outcome [11] 0 0
Subject achieving 15 percentage weight loss or more (Yes/No)
Timepoint [11] 0 0
From baseline (week 0) to end of treatment (week 52)
Secondary outcome [12] 0 0
Subject achieving 20 percentage weight loss or more (Yes/No)
Timepoint [12] 0 0
From baseline (week 0) to end of treatment (week 52)
Secondary outcome [13] 0 0
Subject improving 5 points or more in KCCQ clinical summary score (Yes/No)
Timepoint [13] 0 0
From baseline (week 0) to end of treatment (week 52)
Secondary outcome [14] 0 0
Subject improving 10 points or more in KCCQ clinical summary score (Yes/No)
Timepoint [14] 0 0
From baseline (week 0) to end of treatment (week 52)
Secondary outcome [15] 0 0
Change in KCCQ overall summary score
Timepoint [15] 0 0
From baseline (week 0) to end of treatment (week 52)
Secondary outcome [16] 0 0
Subject achieving threshold for clinically meaningful within-subject change in KCCQ-CSS
Timepoint [16] 0 0
From baseline (week 0) to end of treatment (week 52)
Secondary outcome [17] 0 0
Subject achieving threshold for clinically meaningful within-subject change in 6MWD
Timepoint [17] 0 0
From baseline (week 0) to end of treatment (week 52)
Secondary outcome [18] 0 0
Change in systolic blood pressure (SBP)
Timepoint [18] 0 0
From baseline (week -2) to end of treatment (week 52)
Secondary outcome [19] 0 0
Change in waist circumference
Timepoint [19] 0 0
From baseline (week 0) to end of treatment (visit 52)

Eligibility
Key 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
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
16/03/2021
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
18/04/2023
Sample size
Target
Accrual to date
Final
529
Recruitment in Australia
Recruitment state(s)
ACT,NSW,SA,VIC
Recruitment hospital [1] 0 0
Novo Nordisk Investigational Site - Garran
Recruitment hospital [2] 0 0
Novo Nordisk Investigational Site - Concord
Recruitment hospital [3] 0 0
Novo Nordisk Investigational Site - Liverpool
Recruitment hospital [4] 0 0
Novo Nordisk Investigational Site - Bedford Park
Recruitment hospital [5] 0 0
Novo Nordisk Investigational Site - Geelong
Recruitment postcode(s) [1] 0 0
2605 - Garran
Recruitment postcode(s) [2] 0 0
2139 - Concord
Recruitment postcode(s) [3] 0 0
2170 - Liverpool
Recruitment postcode(s) [4] 0 0
5042 - Bedford Park
Recruitment postcode(s) [5] 0 0
3220 - Geelong
Recruitment outside Australia
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United States of America
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Alabama
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Illinois
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Kansas
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United States of America
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Kentucky
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Louisiana
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Maryland
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Minnesota
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Missouri
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New York
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North Carolina
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Ohio
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Pennsylvania
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Texas
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Argentina
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Caba
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Argentina
State/province [15] 0 0
Ciudad Autónoma de Buenos Aire
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Argentina
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Corrientes
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Argentina
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Morón
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Argentina
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Rosario, Santa Fe
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Canada
State/province [19] 0 0
Ontario
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Canada
State/province [20] 0 0
Quebec
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Czechia
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Jihlava
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Czechia
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Praha 2
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Czechia
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Praha 4
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Czechia
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Praha 7
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Czechia
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Slany
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Czechia
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Tábor
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Denmark
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Region Hovedstaden
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Denmark
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Aarhus N
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Denmark
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Svendborg
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Germany
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Berlin
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Germany
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Dresden
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Germany
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Elsterwerda
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Germany
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Frankfurt
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Germany
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Freiburg
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Germany
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Kassel
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Germany
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Würzburg
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Hungary
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Bács-Kiskun
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Hungary
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Komárom-Esztergom
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Hungary
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Budapest
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Hungary
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Miskolc
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Hungary
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Zalaegerszeg
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Israel
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Jerusalem
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Israel
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Nahariya
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Israel
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Petah-Tikva
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Israel
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Tel Aviv
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Israel
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Tel Hashomer
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Netherlands
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Apeldoorn
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Beverwijk
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Groningen
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Hardenberg
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Leeuwarden
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Netherlands
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Roosendaal
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Poland
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Lodzkie
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Podlaskie
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Chrzanow
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Gdynia
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Poland
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Warsaw
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Poland
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Slaskie
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Spain
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Madrid
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Spain
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Santiago de Compostela
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Spain
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Valencia
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United Kingdom
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Bristol
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United Kingdom
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Dundee
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United Kingdom
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Glasgow
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United Kingdom
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High Wycombe
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United Kingdom
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Liverpool
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United Kingdom
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Manchester
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United Kingdom
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Swindon
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United Kingdom
State/province [69] 0 0
West Sussex

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Novo Nordisk A/S
Address
Country

Ethics approval
Ethics application status

Summary
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 website
https://clinicaltrials.gov/ct2/show/NCT04788511
Trial related presentations / publications
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.
Public notes

Contacts
Principal investigator
Name 0 0
Clinical Transparency (dept. 1452)
Address 0 0
Novo Nordisk A/S
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT04788511