Heart Failure With Preserved Ejection Fraction (HFpEF) and Diabetes Mellitus, Type 2
Conditions
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.
Interventions
DRUGSemaglutide
Participants will receive semaglutide subcutaneous (s.c.; under the skin) injection(s) once-weekly for 52 weeks. Dose will be gradually increased to 2.4 mg: 0.25 mg from week 1 to 4, 0.5 mg from week 5 to 8, 1.0 mg from week 9 to 12, 1.7 mg from week 13 to 16 and 2.4 mg from week 17 to week 52.
DRUGPlacebo (Semaglutide)
Participants will receive semaglutide matching placebo s.c. injection(s) once-weekly for 52 weeks.
Sponsors
Novo Nordisk A/S
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Sponsor staff involved in the clinical trial is masked according to company standard procedures.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in KCCQ (Kansas City Cardiomyopathy Questionnaire) clinical summary score | From baseline (week 0) to end of treatment (week 52) | Score on a scale of 0 to 100 where the score 100 means the least burden for the participant. |
| Change in body weight | From baseline (week 0) to end of treatment (week 52) | Percentage (%) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Hierarchical composite of time to all-cause death | From baseline (week 0) to end of study (week 57) | Measured as total wins for each treatment group. |
| Hierarchical composite of number of heart failure events requiring hospitalisation or urgent heart failure visit | From baseline (week 0) to end of study (week 57) | Measured as total wins for each treatment group |
| Hierarchical composite of time to first heart failure event requiring hospitalisation or urgent heart failure visit | From baseline (week 0) to end of study (week 57) | Measured as total wins for each treatment group. |
| Hierarchical composite of difference at least 15 inKansas City Cardiomyopathy Questionnaire (KCCQ) clinical summary score change from baseline to 52 weeks | From baseline (week 0) to end of study (week 57) | Measured as total wins for each treatment group. |
| Hierarchical composite of difference at least 10 in KCCQ clinical summary score change from baseline to 52 weeks | From baseline (week 0) to end of study (week 57) | Measured as total wins for each treatment group. |
| Hierarchical composite of difference at least 5 in KCCQ clinical summary score change from baseline to 52 weeks | From baseline (week 0) to end of study (week 57) | Measured as total wins for each treatment group. |
| Hierarchical composite of difference at least 30 metres in six-minute walking distance change from baseline to 52 weeks (assessed by the win ratio) | From baseline (week 0) to end of study (week 57) | Measured as total wins for each treatment group. |
| Change in C-Reactive Protein | From baseline (week -2) to end of treatment (week 52) | Presented as ratio to baseline |
| Participant achieving 10% weight loss or more (Yes/No) | From baseline (week 0) to end of treatment (week 52) | Count of participants |
| Participant achieving threshold for clinically meaningful within-subject change in KCCQ-CSS | From baseline (week 0) to end of treatment (week 52) | Count of participants |
| Participant achieving 20% weight loss or more (Yes/No) | From baseline (week 0) to end of treatment (week 52) | Count of participants |
| Participant improving 5 points or more in KCCQ clinical summary score | From baseline (week 0) to end of treatment (week 52) | Count of participants |
| Participant improving 10 points or more in KCCQ clinical summary score (Yes/No) | From baseline (week 0) to end of treatment (week 52) | Count of participants |
| Change in KCCQ overall summary score | From baseline (week 0) to end of treatment (week 52) | Score on a scale of 0 to 100 where the score 100 means the least burden for the participant. |
| Participant achieving threshold for clinically meaningful within-subject change in 6MWD | From baseline (week 0) to end of treatment (week 52) | Count of participants |
| Change in waist circumference | From baseline (week 0) to end of treatment (visit 52) | Measured in centimetre (cm) |
| Change in systolic blood pressure | From baseline (week -2) to end of treatment (week 52) | Measured in millimetre of mercury (mmHg) |
| Change in glycated haemoglobin (HbA1c) | From baseline (week 0) to end of treatment (week 52) | Measured in percentage (%)-point |
| Number of treatment emergent severe or clinically significant hypoglycaemia episodes | From baseline (week 0) to end of trial (week 57) | Count of events |
| Participant achieving 15% weight loss or more (Yes/No) | From baseline (week 0) to end of treatment (week 52) | Count of participants |
| Change in 6-minute walking distance | From baseline (week 0) to end of treatment (week 52) | Measured in metres |
Countries
Argentina, Austria, Canada, Czechia, Germany, Hungary, India, Israel, Italy, Japan, Netherlands, Poland, Spain, Sweden, United Kingdom, United States
Outcome results
None listed