Semaglutide Effects on Heart Disease and Stroke in Patients With Overweight or Obesity
- Conditions
- ObesityOverweight
- Interventions
- Drug: Placebo (semaglutide)
- Registration Number
- NCT03574597
- Lead Sponsor
- Novo Nordisk A/S
- Brief Summary
The researchers are doing the study to see if semaglutide may reduce the risk of having cardiovascular events in patients with overweight or obesity and with prior cardiovascular disease. The participant will either get semaglutide (active medicine) or placebo ("dummy" medicine). Which treatment the participants get is decided by chance. The participant's chance of getting semaglutide or placebo is the same. The participant will get the study medicine in a pen. The participants will need to use the pen to inject the study medicine in a skinfold once a week. The study will last for about 2.5 to 5 years. Participants will have up to 25 clinic visits with the study doctor.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 17609
- Informed consent obtained before any trial-related activities. Trial-related activities are any procedures that are carried out as part of the trial, including activities to determine suitability for the trial
- Male or female, age greater than or equal to 45 years at the time of signing informed consent
- Body mass index (BMI) greater than or equal to 27 kg/m^2
- Have established cardiovascular (CV) disease as evidenced by at least one of the following: prior myocardial infarction; prior stroke (ischemic or haemorrhagic stroke); or symptomatic peripheral arterial disease (PAD), as evidenced by intermittent claudication with ankle-brachial index (ABI) less than 0.85 (at rest), or peripheral arterial revascularization procedure, or amputation due to atherosclerotic disease
Cardiovascular-related:
- Any of the following: myocardial infarction, stroke, hospitalisation for unstable angina pectoris or transient ischaemic attack within the past 60 days prior to the day of screening
- Planned coronary, carotid or peripheral artery revascularisation known on the day of screening
- Presently classified as being in New York Heart Association (NYHA) Class IV heart failure
Glycaemia-related:
- HbA1c greater than or equal to 48 mmol/mol (6.5 %) as measured by the central laboratory at screening
- History of type 1 or type 2 diabetes (history of gestational diabetes is allowed)
- Treatment with glucose-lowering agents within 90 days before screening
- Treatment with any glucagon-like-peptide-1 receptor agonist (GLP-1 RA) within 90 days before screening
General safety:
- History or presence of chronic pancreatitis
- Presence of acute pancreatitis within the past 180 days prior to the day of screening
- Personal or first degree relative(s) history of multiple endocrine neoplasia type 2 or medullary thyroid carcinoma
- End stage renal disease or chronic or intermittent haemodialysis or peritoneal dialysis
- Presence or history of malignant neoplasms within the past 5 years prior to the day of screening. Basal and squamous cell skin cancer and any carcinoma in-situ are allowed
- Severe psychiatric disorder which in the investigator's opinion could compromise compliance with the protocol
- Known or suspected hypersensitivity to trial products or related products
- Previous participation in this trial. Participation is defined as randomisation
- Receipt of any investigational medicinal product within 30 days before screening
- Female who is pregnant, breast-feeding or intends to become pregnant or is of child-bearing potential and not using a highly effective contraceptive method
- Any disorder, unwillingness or inability, which in the investigator's opinion, might jeopardise the participant's safety or compliance with the protocol
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo (semaglutide) Placebo (semaglutide) Participants will receive placebo (semaglutide) as an adjunct to standard-of-care. Estimated trial duration for an individual subject is from 31 to 59 months. Semaglutide Semaglutide Participants will receive semaglutide as an adjunct to standard-of-care. Estimated trial duration for an individual subject is from 31 to 59 months.
- Primary Outcome Measures
Name Time Method Participants From Time of Randomization to First Occurrence of a Composite Outcome Measure Consisting of: Cardiovascular (CV) Death, Non-fatal Myocardial Infarction (MI), or Non-fatal Stroke From randomisation (week 0) up to 240 weeks Number of participants with first occurrence of composite outcome measure consisted of CV death (undetermined cause of death presumed CV death), non-fatal MI, or non-fatal stroke are presented. The outcome measure was evaluated based on data from in-trial observation period. In-trial observation period defined as the period from date of randomisation to one of the following dates, whichever comes first: date of follow-up visit, date when participant withdrew consent, date of last contact with participant for participants who were lost to follow-up (participant did not complete the trial and did not withdraw consent), date of death.
- Secondary Outcome Measures
Name Time Method Participants From Time of Randomisation to CV Death From randomisation (week 0) up to 240 weeks Number of participants with CV death are presented. The outcome measure was evalulated based on data from in-trial observation period. In-trial observation period defined as the period from date of randomisation to one of the following dates, whichever comes first: date of follow-up visit, date when participant withdrew consent, date of last contact with participant for participants who were lost to follow-up (participant did not complete the trial and did not withdraw consent), date of death.
Participants From Time of Randomisation to First Occurrence of a Composite Heart Failure (HF) Outcome Measure Consisting of: HF Hospitalisation, Urgent HF Visit or CV Death From randomisation (week 0) up to 240 weeks Number of participants with first occurrence of a composite HF outcome measure consisted of HF hospitalisation, urgent HF visit or CV death are presented. The outcome measure was evaluated based on data from in-trial observation period. In-trial observation period defined as the period from date of randomisation to one of the following dates, whichever comes first: date of follow-up visit, date when participant withdrew consent, date of last contact with participant for participants who were lost to follow-up (participant did not complete the trial and did not withdraw consent), date of death.
Participants From Time of Randomisation to All-cause Death From randomisation (week 0) up to 240 weeks Number of participants with all-cause death are presented. The outcome measure was evaluated based on data from in-trial observation period. In-trial observation period defined as the period from date of randomisation to one of the following dates, whichever comes first: date of follow-up visit, date when participant withdrew consent, date of last contact with participant for participants who were lost to follow-up (participant did not complete the trial and did not withdraw consent), date of death.
Participants From Time of Randomisation to First Occurrence of an Expanded Composite CV Outcome Measure Consisting of: CV Death, Non-fatal MI, Non-fatal Stroke, Coronary Revascularisation or Unstable Angina Pectoris (UAP) Requiring Hospitalisation From randomisation (week 0) up to 240 weeks Number of participants with first occurrence of an expanded composite CV outcome measure consisted of CV death, non-fatal MI, non-fatal stroke, coronary revascularisation or UAP requiring hospitalisation are presented. The outcome measure was evaluated based on data from in-trial observation period. In-trial observation period defined as the period from date of randomisation to one of the following dates, whichever comes first: date of follow-up visit, date when participant withdrew consent, date of last contact with participant for participants who were lost to follow-up (participant did not complete the trial and did not withdraw consent), date of death.
Participants From Time of Randomisation to First Occurrence of a Composite Outcome Measure Consisting of: All-cause Death, Non-fatal MI, or Non-fatal Stroke From randomisation (week 0) up to 240 weeks Number of participants with first occurrence of a composite outcome measure consisted of all-cause death, non-fatal MI, or non-fatal stroke are presented. The outcome measure was evaluated based on data from in-trial observation period. In-trial observation period defined as the period from date of randomisation to one of the following dates, whichever comes first: date of follow-up visit, date when participant withdrew consent, date of last contact with participant for participants who were lost to follow-up (participant did not complete the trial and did not withdraw consent), date of death.
Participants From Time of Randomisation to First Occurrence of Non-fatal MI From randomisation (week 0) up to 240 weeks Number of participants with first occurrence of non-fatal MI are presented. The outcome measure was evaluated based on data from in-trial observation period. In-trial observation period defined as the period from date of randomisation to one of the following dates, whichever comes first: date of follow-up visit, date when participant withdrew consent, date of last contact with participant for participants who were lost to follow-up (participant did not complete the trial and did not withdraw consent), date of death.
Participants From Time of Randomisation to First Occurrence of Non-fatal Stroke From randomisation (week 0) up to 240 weeks Number of participants with first occurrence of non-fatal stroke are presented. The outcome measure was evaluated based on data from in-trial observation period. In-trial observation period defined as the period from date of randomisation to one of the following dates, whichever comes first: date of follow-up visit, date when participant withdrew consent, date of last contact with participant for participants who were lost to follow-up (participant did not complete the trial and did not withdraw consent), date of death.
Participants From Time of Randomisation to First Occurrence of Coronary Revascularisation From randomisation (week 0) up to 240 weeks Number of participants with first occurrence of coronary revascularisation are presented. The outcome measure was evaluated based on data from in-trial observation period. In-trial observation period defined as the period from date of randomisation to one of the following dates, whichever comes first: date of follow-up visit, date when participant withdrew consent, date of last contact with participant for participants who were lost to follow-up (participant did not complete the trial and did not withdraw consent), date of death.
Participants From Time of Randomisation to First Occurrence of UAP Requiring Hospitalisation From randomisation (week 0) up to 240 weeks Number of participants with first occurrence of UAP requiring hospitalisation are presented. The outcome measure was evaluated based on data from in-trial observation period. In-trial observation period defined as the period from date of randomisation to one of the following dates, whichever comes first: date of follow-up visit, date when participant withdrew consent, date of last contact with participant for participants who were lost to follow-up (participant did not complete the trial and did not withdraw consent), date of death.
Participants From Time of Randomisation to First Occurrence of HF Requiring Hospitalisation or Urgent HF Visit From randomisation (week 0) up to 240 weeks Number of participants with first occurrence of HF requiring hospitalisation or urgent HF visit are presented. The outcome measure was evaluated based on data from in-trial observation period. In-trial observation period defined as the period from date of randomisation to one of the following dates, whichever comes first: date of follow-up visit, date when participant withdrew consent, date of last contact with participant for participants who were lost to follow-up (participant did not complete the trial and did not withdraw consent), date of death.
Participants From Time of Randomisation to First Occurrence of Glycosylated Haemoglobin (HbA1c) Greater Than Equals to (≥) 48 Millimole Per Mole (mmol/Mol) (6.5 Percentage [%]) From randomisation (week 0) up to 240 weeks Number of participants with first occurrence of HbA1c ≥ 48 mmol/mol (6.5%) are presented. The outcome measure was evaluated based on data from in-trial observation period. In-trial observation period defined as the period from date of randomisation to one of the following dates, whichever comes first: date of follow-up visit, date when participant withdrew consent, date of last contact with participant for participants who were lost to follow-up (participant did not complete the trial and did not withdraw consent), date of death.
Participants From Time of Randomisation to First Occurrence of a 5-component Composite Nephropathy Outcome Measure From randomisation (week 0) up to 240 weeks Number of participants with first occurrence of a 5-component composite nephropathy outcome measure consisted of onset of persistent macroalbuminuria (UACR \> 300 milligram per gram \[mg/g\]), persistent 50% reduction in estimated glomerular filtration rate (eGFR) compared with baseline (randomisation), onset of persistent eGFR \< 15 ml/min/1.73m\^2, initiation of chronic renal replacement therapy (dialysis or transplantation) or renal death. The outcome measure was evaluated based on data from in-trial observation period. In-trial observation period defined as the period from date of randomisation to one of the following dates, whichever comes first: date of follow-up visit, date when participant withdrew consent, date of last contact with participant for participants who were lost to follow-up (participant did not complete the trial and did not withdraw consent), date of death.
Participants From Time of Randomisation to HbA1c ≥ 39 mmol/Mol (5.7%) (for Participants With a Screening HbA1c <39 mmol/Mol [5.7%]) From randomisation (week 0) up to 240 weeks Number of participants with HbA1c ≥ 39 mmol/mol (5.7%) are presented. The outcome measure was evaluated based on data from in-trial observation period. In-trial observation period defined as the period from date of randomisation to one of the following dates, whichever comes first: date of follow-up visit, date when participant withdrew consent, date of last contact with participant for participants who were lost to follow-up (participant did not complete the trial and did not withdraw consent), date of death.
Participants With HbA1c < 39 mmol/Mol (5.7%) (for Participants With a Screening HbA1c ≥ 39 mmol/Mol [5.7%]) At week 52, week 104 Number of participants with HbA1c \< 39 mmol/mol (5.7%) are presented. The outcome measure was evaluated based on data from in-trial observation period. In-trial observation period defined as the period from date of randomisation to one of the following dates, whichever comes first: date of follow-up visit, date when participant withdrew consent, date of last contact with participant for participants who were lost to follow-up (participant did not complete the trial and did not withdraw consent), date of death.
Change in Systolic Blood Pressure (SBP) Week 0, week 104 Change in SBP from randomisation (week 0) to week 104 is presented. The outcome measure was evaluated based on data from in-trial observation period. In-trial observation period defined as the period from date of randomisation to one of the following dates, whichever comes first: date of follow-up visit, date when participant withdrew consent, date of last contact with participant for participants who were lost to follow-up (participant did not complete the trial and did not withdraw consent), date of death.
Change in Diastolic Blood Pressure (DBP) Week 0, week 104 Change in DBP from randomisation (week 0) to week 104 is presented. The outcome measure was evaluated based on data from in-trial observation period. In-trial observation period defined as the period from date of randomisation to one of the following dates, whichever comes first: date of follow-up visit, date when participant withdrew consent, date of last contact with participant for participants who were lost to follow-up (participant did not complete the trial and did not withdraw consent), date of death.
Change in Pulse Week 0, week 104 Change in pulse from randomisation (week 0) to week 104 is presented. The outcome measure was evaluated based on data from in-trial observation period. In-trial observation period defined as the period from date of randomisation to one of the following dates, whichever comes first: date of follow-up visit, date when participant withdrew consent, date of last contact with participant for participants who were lost to follow-up (participant did not complete the trial and did not withdraw consent), date of death.
Change in High Sensitivity C-Reactive Protein (hsCRP) - Ratio to Baseline Week 0, week 104 Change in hsCRP (milligram per liter \[mg/L\]) from randomisation (week 0) to week 104 presented as ratio to baseline (week 0). The outcome measure was evaluated based on data from in-trial observation period. In-trial observation period defined as the period from date of randomisation to one of the following dates, whichever comes first: date of follow-up visit, date when participant withdrew consent, date of last contact with participant for participants who were lost to follow-up (participant did not complete the trial and did not withdraw consent), date of death.
Change in Total Cholesterol - Ratio to Baseline Week 0, week 104 Change in total cholesterol (milligram per deciliter \[mg/dL\]) from randomisation (week 0) to week 104 is presented as ratio to baseline (week 0). The outcome measure was evaluated based on data from in-trial observation period. In-trial observation period defined as the period from date of randomisation to one of the following dates, whichever comes first: date of follow-up visit, date when participant withdrew consent, date of last contact with participant for participants who were lost to follow-up (participant did not complete the trial and did not withdraw consent), date of death.
Change in High Density Lipoprotein (HDL) Cholesterol - Ratio to Baseline Week 0, week 104 Change in HDL (mg/dL) from randomisation (week 0) to week 104 is presented as ratio to baseline (week 0). The outcome measure was evaluated based on data from in-trial observation period. In-trial observation period defined as the period from date of randomisation to one of the following dates, whichever comes first: date of follow-up visit, date when participant withdrew consent, date of last contact with participant for participants who were lost to follow-up (participant did not complete the trial and did not withdraw consent), date of death.
Change in Low Density Lipoprotein (LDL) Cholesterol - Ratio to Baseline Week 0, week 104 Change in LDL (mg/dL) from randomisation (week 0) to week 104 is presented as ratio to baseline (week 0). The outcome measure was evaluated based on data from in-trial observation period. In-trial observation period defined as the period from date of randomisation to one of the following dates, whichever comes first: date of follow-up visit, date when participant withdrew consent, date of last contact with participant for participants who were lost to follow-up (participant did not complete the trial and did not withdraw consent), date of death.
Change in Triglycerides - Ratio to Baseline Week 0, week 104 Change in triglycerides (mg/dL) from randomisation (week 0) to week 104 is presented as ratio to baseline (week 0). The outcome measure was evaluated based on data from in-trial observation period. In-trial observation period defined as the period from date of randomisation to one of the following dates, whichever comes first: date of follow-up visit, date when participant withdrew consent, date of last contact with participant for participants who were lost to follow-up (participant did not complete the trial and did not withdraw consent), date of death.
Change in Body Weight Week 0, week 104 Percentage change in body weight from randomisation (week 0) to week 104 is presented. The outcome measure was evaluated based on data from in-trial observation period. In-trial observation period defined as the period from date of randomisation to one of the following dates, whichever comes first: date of follow-up visit, date when participant withdrew consent, date of last contact with participant for participants who were lost to follow-up (participant did not complete the trial and did not withdraw consent), date of death.
Change in Waist Circumference Week 0, week 104 Change is waist circumference from randomisation (week 0) to week 104 is presented. The outcome measure was evaluated based on data from in-trial observation period. In-trial observation period defined as the period from date of randomisation to one of the following dates, whichever comes first: date of follow-up visit, date when participant withdrew consent, date of last contact with participant for participants who were lost to follow-up (participant did not complete the trial and did not withdraw consent), date of death.
Change From Randomisation (Week 0) in Participant Reported Outcome (PRO): EuroQol Five Dimensions Five Level Questionnaire (EQ-5D-5L) Index Score to Week 104 Week 0, week 104 EQ-5D-5L is a PRO tool used to estimate impact on participant's health-related quality of life and provides a description of their problems by dimensions (descriptive system). EQ-5D has 5 dimensions: mobility, self-care, usual activities, pain, anxiety/depression, and each dimension has 5 levels: not at all, mild, moderate, severe, extreme. Participant marks most appropriate statement in each dimension, resulting in 1-digit number and digits from 5 dimensions can be combined in 5-digit number describing participant's health state. Index score records an average health status according to dimensions using an algorithm, ranges 0-1 with higher score indicates better health status. Outcome measure was evaluated based on data from in-trial observation period (defined as date of randomisation to one of the dates, whichever comes first: date of follow-up visit, date when participant withdrew consent, date of last contact with participant \[who were lost to follow-up\], date of death).
Change From Randomisation (Week 0) in PRO: EuroQol Five Dimensions Visual Analogue Scale (EQ-5D-VAS) to Week 104 Week 0, week 104 EQ-5D-5L is a PRO tool used to estimate impact on participant's health-related quality of life and provides a description of their problems by dimensions (descriptive system). EQ-5D has 5 dimensions: mobility, self-care, usual activities, pain, anxiety/depression, and each dimension has 5 levels: not at all, mild, moderate, severe, extreme. Participant marks most appropriate statement in each dimension, resulting in 1-digit number and digits from 5 dimensions can be combined in 5-digit number describing participant's health state. VAS component records a participant's overall self-rated health on a range of 0-100 with higher score indicates better self-reported health status. Outcome measure was evaluated based on data from in-trial observation period (defined as date of randomisation to one of the dates, whichever comes first: date of follow-up visit, date when participant withdrew consent, date of last contact with participant \[who were lost to follow-up\], date of death).
Change in HbA1c - Percentage Week 0, week 104 Change in HbA1c (percentage) from randomisation (week 0) to week 104 is presented. The outcome measure was evaulated based on data from in-trial observation period. In-trial observation period defined as the period from date of randomisation to one of the following dates, whichever comes first: date of follow-up visit, date when participant withdrew consent, date of last contact with participant for participants who were lost to follow-up (participant did not complete the trial and did not withdraw consent), date of death.
Change in HbA1c - mmol/Mol Week 0, week 104 Change in HbA1c (mmol/mol) from randomisation (week 0) to week 104 is presented. The outcome measure was evaulated based on data from in-trial observation period. In-trial observation period defined as the period from date of randomisation to one of the following dates, whichever comes first: date of follow-up visit, date when participant withdrew consent, date of last contact with participant for participants who were lost to follow-up (participant did not complete the trial and did not withdraw consent), date of death.
Trial Locations
- Locations (830)
Synexus Rsch /Cnt Phnx Med C
🇺🇸Phoenix, Arizona, United States
Centre de Recherche Clinique Portes Du Sud
🇫🇷Venissieux, France
Velocity Nova Sp. z o.o.
🇵🇱Pulawy, Poland
Central Alabama Research
🇺🇸Birmingham, Alabama, United States
Univ of Alabama Birmingham
🇺🇸Birmingham, Alabama, United States
Healthscan Clinical Trials,LLC.
🇺🇸Montgomery, Alabama, United States
Synexus Clinical Research US, Inc./Tatum
🇺🇸Glendale, Arizona, United States
Synexus Clinical Research
🇺🇸Glendale, Arizona, United States
National Heart Institute Cal
🇺🇸Beverly Hills, California, United States
FDRC
🇺🇸Costa Mesa, California, United States
Scroll for more (820 remaining)Synexus Rsch /Cnt Phnx Med C🇺🇸Phoenix, Arizona, United States