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Trial · Interventional

CompletedPhase 3Results postedRegistry data

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

Short name STEP-HFpEF

NCTNCT04788511 (opens ClinicalTrials.gov in a new tab)Other idEX9536-4665Other idU1111-1243-4358Other id2019-004452-11Other id2019

Overview

Status
Completed
Phase
Phase 3
Enrollment
529 participants (actual)
Sponsor
Novo Nordisk A/S · Industry
Design
Randomized · Double masking
Countries
13 countries

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

Start
16 Mar 2021
Primary completion
18 Apr 2023
Completion
18 Apr 2023
First posted
9 Mar 2021
Last update posted
5 Dec 2025
Conditions
Obesity

Timeline

1 trial · 1 completed · 1 with posted results

  • Completed
  • Ongoing
  • Not yet recruiting
  • Stopped
  • Estimated dates (est.)
  • Results posted
2021202220232024
  1. Ph 3

    STEP-HFpEF

    NCT04788511

    16 Mar 2021 to 18 Apr 2023

Registry summary

Text and fields below are the sponsor's entries at ClinicalTrials.gov, shown as posted.

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.

Interventions

  • SemaglutideDrug
  • Placebo (semaglutide)Drug

Arms2

  • 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.

Primary outcomes2

Outcomes the sponsor listed as primary.

  1. Change in Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ-CSS)

    Time frame · From baseline (week 0) to end of treatment (week 52)

    Registry description

    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.

  2. Change in Body Weight

    Time frame · From baseline (week 0) to end of treatment (week 52)

    Registry description

    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.

Secondary outcomes(13)
  1. Change in Six-minute Walking Distance (6MWD)

    Time frame · From baseline (week 0) to end of treatment (week 52)

    Registry description

    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.

  2. The Hierarchical Composite Endpoint: Percentage of Wins of Participant Pairs

    Time frame · From baseline (week 0) to end of study (week 57)

    Registry description

    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.

  3. Change in C-Reactive Protein (CRP): Ratio to Baseline

    Time frame · From baseline (week -2) to end of treatment (week 52)

    Registry description

    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.

  4. Percentage of Participants Achieving 10 Percent (%) Weight Loss (Yes/No)

    Time frame · From baseline (week 0) to end of treatment (week 52)

    Registry description

    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.

  5. Percentage of Participants Achieving 15% Weight Loss (Yes/No)

    Time frame · From baseline (week 0) to end of treatment (week 52)

    Registry description

    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.

  6. Percentage of Participants Achieving 20% Weight Loss (Yes/No)

    Time frame · From baseline (week 0) to end of treatment (week 52)

    Registry description

    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.

  7. Percentage of Participants Improving 5 Points or More in KCCQ Clinical Summary Score (Yes/No)

    Time frame · From baseline (week 0) to end of treatment (week 52)

    Registry description

    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.

  8. Percentage of Participants Improving 10 Points or More in KCCQ Clinical Summary Score (Yes/No)

    Time frame · From baseline (week 0) to end of treatment (week 52)

    Registry description

    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.

  9. Change in KCCQ Overall Summary Score (KCCQ-OSS)

    Time frame · From baseline (week 0) to end of treatment (week 52)

    Registry description

    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.

  10. Percentage of Participants Achieving Threshold for Clinically Meaningful Within-participants Change in KCCQ-CSS (PGI-S)

    Time frame · From baseline (week 0) to end of treatment (week 52)

    Registry description

    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.

  11. Percentage of Participants Achieving Threshold for Clinically Meaningful Within-participants Change in 6MWD (PGI-S)

    Time frame · From baseline (week 0) to end of treatment (week 52)

    Registry description

    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.

  12. Change in Systolic Blood Pressure (SBP)

    Time frame · From baseline (week -2) to end of treatment (week 52)

    Registry description

    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.

  13. Change in Waist Circumference

    Time frame · From baseline (week 0) to end of treatment (visit 52)

    Registry description

    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.

Posted results

Values are shown as posted at ClinicalTrials.gov, with their units. PepBank has not converted, pooled or compared them.

Primary outcome results

Primary outcomeMean· From baseline (week 0) to end of treatment (week 52)

Change in Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ-CSS)

GroupValue (Score on a scale)Spread
Semaglutide 2.4 mg16.817.9
Placebo10.317.3
Primary outcomeMean· From baseline (week 0) to end of treatment (week 52)

Change in Body Weight

GroupValue (Percentage of body weight)Spread
Semaglutide 2.4 mg-13.98.1
Placebo-2.55.6
Secondary and other outcome results(6)
Secondary outcomeMean· From baseline (week 0) to end of treatment (week 52)

Change in Six-minute Walking Distance (6MWD)

GroupValue (Meters)Spread
Semaglutide 2.4 mg23.559.2
Placebo5.862.7
Secondary outcomeNumber· From baseline (week 0) to end of study (week 57)

The Hierarchical Composite Endpoint: Percentage of Wins of Participant Pairs

GroupValue (Percentages of wins of participant pairs)
Semaglutide 2.4 mg60.1
Placebo34.9
Secondary outcomeGeometric mean· From baseline (week -2) to end of treatment (week 52)

Change in C-Reactive Protein (CRP): Ratio to Baseline

GroupValue (Ratio of C-reactive protein)Spread
Semaglutide 2.4 mg0.55121.5
Placebo0.92105.3
Secondary outcomeNumber· From baseline (week 0) to end of treatment (week 52)

Percentage of Participants Achieving 10 Percent (%) Weight Loss (Yes/No)

GroupValue (Percentage of participants)
Semaglutide 2.4 mg34.1
Placebo90.5
Secondary outcomeNumber· From baseline (week 0) to end of treatment (week 52)

Percentage of Participants Achieving 15% Weight Loss (Yes/No)

GroupValue (Percentage of participants)
Semaglutide 2.4 mg56.1
Placebo97.9
Secondary outcomeNumber· From baseline (week 0) to end of treatment (week 52)

Percentage of Participants Achieving 20% Weight Loss (Yes/No)

GroupValue (Percentage of participants)
Semaglutide 2.4 mg76.4
Placebo99.6

Adverse events, as posted

Adverse events as posted: participants affected out of participants at risk, by group
GroupDeathsSerious eventsOther events
Semaglutide 2.4 mgParticipants with obesity (BMI ≥30.0 kg/m\^2) related heart failure with preserved ejection fraction received semaglutide 2.4 mg once weekly by subcutaneous injection (in the abdomen, thigh or upper arm). Participants initially received 0.25 mg of semaglutide. The dose was then escalated every fourth week with increments of 0.25 mg for 16 weeks until the target dose of 2.4 mg was reached. The treatment period was 52 weeks.3 / 26335 / 26393 / 263
PlaceboParticipants with obesity (BMI ≥30.0 kg/m\^2) related heart failure with preserved ejection fraction received placebo once weekly by subcutaneous injection (in the abdomen, thigh or upper arm) for 52 weeks. The dose escalation and maintenance of placebo matched that of semaglutide.4 / 26671 / 26657 / 266

Each cell reads participants affected / participants at risk, as the registry posted them.

Registry data comes from ClinicalTrials.gov. Study results come from studies, not from the registry. How PepBank works

Studies7

Studies that cite this trial.

Studies with results

4 studies on this page

Indexing hint: Randomized controlled trial · 2024

7 results

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.

Butler et al. 2024Lancet (London, England)cited by 296

PMID 38599221PMC11317105DOI 10.1016/s0140-6736(24)00469-0PUB-38599221

Rights unknown7 results

Indexing hint: Randomized controlled trial · 2024

9 results

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.

Shah et al. 2024European heart journalcited by 68

PMID 38739118PMC11400859DOI 10.1093/eurheartj/ehae322PUB-38739118

CC BY9 results

Indexing hint: Randomized controlled trial · 2024

4 results

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.

Kosiborod et al. 2024Lancet (London, England)cited by 232

PMID 39222642DOI 10.1016/s0140-6736(24)01643-xPUB-39222642

Full text at the publisher4 results

Indexing hint: Randomized controlled trial · 2023

6 results

Semaglutide in Patients with Heart Failure with Preserved Ejection Fraction and Obesity.

Kosiborod et al. 2023The New England journal of medicinecited by 1,372

PMID 37622681DOI 10.1056/nejmoa2306963PUB-37622681

Full text at the publisher6 results

More studies

3 studies on this page

PubMed tag: none · 2024

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.

Kosiborod et al. 2024Circulationcited by 82

PMID 37952180PMC10782938DOI 10.1161/circulationaha.123.067505PUB-37952180

Free to read · publisher termsCC BY-NC-ND
Read at source

PubMed tag: none · 2023

Semaglutide in HFpEF across obesity class and by body weight reduction: a prespecified analysis of the STEP-HFpEF trial.

Borlaug et al. 2023Nature medicinecited by 183

PMID 37635157PMC10504076DOI 10.1038/s41591-023-02526-xPUB-37635157

CC BY
Download PDF

PubMed tag: none · 2023

Semaglutide in Patients With Obesity and Heart Failure Across Mildly Reduced or Preserved Ejection Fraction.

Butler et al. 2023Journal of the American College of Cardiologycited by 65

PMID 37993201PMC11185158DOI 10.1016/j.jacc.2023.09.811PUB-37993201

Free to read · publisher termsCC BY-NC-ND
Read at source

Eligibility

Who could join, as posted.

Sex
All
Age
from 18 Years
Healthy volunteers
Not accepted
Inclusion and exclusion criteria, as posted
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

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