NCT03914326
Completed
Phase 3
Semaglutide Cardiovascular Outcomes Trial in Patients With Type 2 Diabetes
Overview
- Phase
- Phase 3
- Status
- Completed
- Sponsor
- Novo Nordisk A/S
- Enrollment
- 9,651
- Locations
- 482
- Primary Endpoint
- Number of Participants From Randomization to First Occurrence of a Major Adverse Cardiovascular Event (MACE), a Composite Endpoint Consisting of: Cardiovascular (CV) Death/Non-fatal Myocardial Infarction/Non-fatal Stroke
Overview
Brief Summary
The researchers are doing this study to look whether the type 2 diabetes medicine, semaglutide, has a positive effect on heart disease. Participants will either get semaglutide tablets or placebo tablets ("dummy" medicine) - which treatment is decided by chance. Participants must take one tablet with water every morning on an empty stomach and not eat or drink anything for at least 30 minutes. The study will last for about 3.5-5 years. Participants will have up to 25 clinic visits and 1 phone call with the study doctor. Women cannot be in the study if pregnant, breast-feeding or if they plan to become pregnant during the study period.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description
Sponsor staff involved in the clinical trial is masked according to company standard procedures
Eligibility Criteria
- Ages
- 50 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Male or female, age equal to or above 50 years at the time of signing informed consent
- •Diagnosed with type 2 diabetes mellitus
- •HbA1c 6.5% - 10.0% (47 - 86 mmol/mol) (both inclusive) (latest available and no more than 30 days old local laboratory assessment based on medical records or point of care measurement)
- •At least one of the below conditions (a-d):
- •a) Coronary heart disease defined as at least one of the following: i. Prior myocardial infarction ii. Prior coronary revascularisation procedure iii. 50% or above stenosis in coronary artery documented by cardiac catheterisation, computerized tomography coronary angiography iv. Coronary heart disease with ischaemia documented by stress test with any imaging modality b) Cerebrovascular disease defined as at least one of the following: i. Prior stroke ii. Prior carotid artery revascularisation procedure iii.50% or above stenosis in carotid artery documented by X-ray angiography, magnetic resonance angiography, computerized tomography angiography or Doppler ultrasound c) Symptomatic peripheral artery disease (PAD) defined as at least one of the following: i. Intermittent claudication with an Ankle-brachial index (ABI) below 0.85 at rest ii. Intermittent claudication with a 50% or above stenosis in peripheral artery (excluding carotid) documented by X-ray angiography, magnetic resonance angiography, computerized tomography angiography or Doppler ultrasound iii. Prior peripheral artery (excluding carotid) revascularization procedure iv. Lower extremity amputation at or above ankle due to atherosclerotic disease (excluding e.g. trauma or osteomyelitis) d) Chronic kidney disease defined as: i. eGFR below 60 mL/min/1.73 m\^2 (based on medical records using latest available and no more than 6 months old assessment)
Exclusion Criteria
- •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
- •Heart failure presently classified as being in New York Heart Association Class IV
- •Treatment with any glucagon-like peptide-1 receptor agonist within 30 days before screening
Arms & Interventions
Oral semaglutide
Experimental
One tablet daily for 3.5 to 5 years
Intervention: Semaglutide (Drug)
Placebo
Placebo Comparator
One tablet daily for 3.5 to 5 years
Intervention: Placebo (semaglutide) (Drug)
Outcomes
Primary Outcomes
Number of Participants From Randomization to First Occurrence of a Major Adverse Cardiovascular Event (MACE), a Composite Endpoint Consisting of: Cardiovascular (CV) Death/Non-fatal Myocardial Infarction/Non-fatal Stroke
Time Frame: From randomisation (week 0) up to week 265
Number of participants with first occurrence of EAC (event adjudication committee) confirmed major adverse cardiovascular event (MACE), a composite end-point. i.e., from time of randomization to first occurrence of cardiovascular (CV) death, non-fatal myocardial infarction and non-fatal stroke combined data during in-trial period were reported. In-trial observation period was defined as the period from date of randomization to the first of (both inclusive): date of follow-up visit, date when participant withdrew consent, date of last contact with participant (for participant lost to follow-up), and date of death.
Secondary Outcomes
- Number of Participants From Randomization to Time of Occurrence of CV Death(From randomisation (week 0) up to week 265)
- Number of Participants From Randomization to First Occurrence of CV Death;Renal Death;Onset of Persistent≥50% Reduction in eGFR(CKD-EPI);Onset of Persistent eGFR(CKD-EPI)<15 mL/Min/1.73m^2;Initiation of Chronic Renal Replacement Therapy(From randomisation (week 0) up to week 265)
- Number of Participants From Randomization to First Occurrence of Major Adverse Limb Events (MALE), a Composite Endpoint Consisting of: Acute Limb Ischemia Hospitalisation/Chronic Limb Ischemia Hospitalisation(From randomisation (week 0) up to week 265)
- Number of Participants From Randomisation to First Occurrence of an Expanded MACE Composite Endpoint Consisting of: CV Death/Non-fatal Myocardial Infarction/ Non-fatal Stroke/Coronary Revascularisation/Unstable Angina Pectoris Requiring Hospitalisation(From randomisation (week 0) up to week 265)
- Number of Participants From Randomisation to First Occurrence of a Composite Endpoint Consisting of : All-cause Death/ Non-fatal MI/ Non-fatal Stroke(From randomisation (week 0) up to week 265)
- Number of Participants From Randomisation to First Occurrence of a Composite Heart Failure Endpoint Consisting of: CV Death/Heart Failure Requiring Hospitalisation/Urgent Heart Failure Visit(From randomisation (week 0) up to week 265)
- Number of Participants From Randomization to First Occurrence of CKD Endpoint:Renal Death;Onset of Persistent≥50% Reduction in eGFR (CKD-EPI);Onset of Persistent eGFR(CKD-EPI)<15 mL/Min/1.73 m^2;Initiation of Chronic Renal Replacement Therapy(From randomisation (week 0) up to week 265)
- Number of Participants From Randomisation to Time to Occurrence of All-cause Death(From randomisation (week 0) up to week 265)
- Number of Participants From Randomisation to First Occurrence of Non-fatal Myocardial Infarction (MI)(From randomisation (week 0) up to week 265)
- Number of Participants From Randomisation to First Occurrence of Non-fatal Stroke(From randomisation (week 0) up to week 265)
- Change From Baseline in Body Weight(Baseline (Week 0), Week 104)
- Number of Participants From Randomisation to First Occurrence of Heart Failure Requiring Hospitalisation or Urgent Heart Failure Visit(From randomisation (week 0) up to week 265)
- Number of Participants From Randomisation to First Occurrence of Coronary Revascularisation(From randomisation (week 0) up to week 265)
- Number of Participants From Randomisation to First Occurrence of Unstable Angina Requiring Hospitalisation(From randomisation (week 0) up to week 265)
- Number of Participants From Randomisation to Time to Occurrence of Renal Death(From randomisation (week 0) up to week 265)
- Number of Participants From Randomisation to First Occurrence of Onset of Persistent 50% or More Reduction in eGFR(From randomisation (week 0) up to week 265)
- Number of Participants From Randomisation to First Occurrence of Onset of Persistent eGFR (CKD-EPI) Below 15 mL/Min/1.73 m^2(From randomisation (week 0) up to week 265)
- Number of Participants From Randomisation to First Occurrence of Initiation of Chronic Renal Replacement Therapy (Dialysis or Kidney Transplantation)(From randomisation (week 0) up to week 265)
- Number of Participants From Randomisation to First Occurrence of Acute Limb Ischemia(From randomisation (week 0) up to week 265)
- Number of Participants From Randomisation to First Occurrence of Chronic Limb Ischemia Hospitalisation(From randomisation (week 0) up to week 265)
- Annual Rate of Change in eGFR (CKD-EPI) (Total eGFR Slope)(From randomisation (week 0) up to week 260)
- Change From Baseline in Glycosylated Haemoglobin (HbA1c)(Baseline (Week 0), Week 104)
- Number of Severe Hypoglycaemic Episodes(From randomisation (week 0) up to week 265)
- Number of Participants From Randomisation to First Occurrence of a Severe Hypoglycaemic Episode(From randomisation (week 0) up to week 265)
Investigators
Study Sites (482)
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