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A Heart Disease Study of Semaglutide in Patients With Type 2 Diabetes

Phase 3
Completed
Conditions
Diabetes Mellitus, Type 2
Interventions
Drug: Placebo (semaglutide)
Registration Number
NCT03914326
Lead Sponsor
Novo Nordisk A/S
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.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
9642
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

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
PlaceboPlacebo (semaglutide)One tablet daily for 3.5 to 5 years
Oral semaglutideSemaglutideOne tablet daily for 3.5 to 5 years
Primary Outcome Measures
NameTimeMethod
Time to first occurrence of a major adverse cardiovascular event (MACE), a composite endpoint consisting of: cardiovascular (CV) death/non-fatal myocardial infarction/non-fatal strokeFrom randomisation (week 0) to end-of-trial (up to 61 months or more) (trial is event driven)

Months

Secondary Outcome Measures
NameTimeMethod
Time to first occurrence of a composite CKD endpointFrom randomisation (week 0) to end-of-trial (up to 61 months or more)

Time to first occurrence of a composite CKD endpoint consisting of: renal death/onset of persistent 50% or more reduction in eGFR (CKD-EPI)/onset of persistent eGFR (CKD-EPI) below 15 mL/min/1.73 m\^2/initiation of chronic renal replacement therapy (dialysis or kidney transplantation).

Unit of assessment: Months

Time to first occurrence of non-fatal strokeFrom randomisation (week 0) to end-of-trial (up to 61 months or more)

Months

Annual rate of change in eGFR (CKD-EPI) (total eGFR slope)From randomisation (week 0) to end-of-trial (up to 61 months or more)

ml/min/1.73 m\^2 per year

Time to occurrence of CV deathFrom randomisation (week 0) to end-of-trial (up to 61 months or more)

Months

Time to first occurrence of onset of persistent eGFR (CKD-EPI) below 15 mL/min/1.73 m^2From randomisation (week 0) to end-of-trial (up to 61 months or more)

Months

Time to first occurrence of initiation of chronic renal replacement therapy (dialysis or kidney transplantation)From randomisation (week 0) to end-of-trial (up to 61 months or more)

Months

Time to first occurrence of a composite endpoint consisting of: all-cause death/non-fatal myocardial infarction/non-fatal strokeFrom randomisation (week 0) to end-of-trial (up to 61 months or more)

Months

Time to first occurrence of a composite endpointFrom randomisation (week 0) to end-of-trial (up to 61 months or more)

Time to first occurrence of a composite endpoint consisting of: CV death/renal death/onset of persistent 50% or more reduction in estimated glomerular filtration rate (eGFR) (chronic kidney disease - epidemiology collaboration (CKD-EPI)) (compared with baseline)/onset of persistent eGFR (CKD-EPI) below 15 mL/min/1.73 m\^2/initiation of chronic renal replacement therapy (dialysis or kidney transplantation).

Unit of assessment: Months

Time to first occurrence of a composite heart failure endpoint consisting of: CV death/heart failure requiring hospitalisation/urgent heart failure visitFrom randomisation (week 0) to end-of-trial (up to 61 months or more)

Months

Time to first occurrence of major adverse limb events (MALE), a composite endpoint consisting of: acute limb ischemia hospitalisation/chronic limb ischemia hospitalisationFrom randomisation (week 0) to end-of-trial (up to 61 months or more)

Months

Time to first occurrence of non-fatal myocardial infarction (MI)From randomisation (week 0) to end-of-trial (up to 61 months or more)

Months

Time to first occurrence of heart failure requiring hospitalisationFrom randomisation (week 0) to end-of-trial (up to 61 months or more)

Months

Time to first occurrence of coronary revascularisationFrom randomisation (week 0) to end-of-trial (up to 61 months or more)

Months

Time to first occurrence of unstable angina requiring hospitalisationFrom randomisation (week 0) to end-of-trial (up to 61 months or more)

Months

Time to first occurrence of acute limb ischemiaFrom randomisation (week 0) to end-of-trial (up to 61 months or more)

Months

Time to first occurrence of chronic limb ischemiaFrom randomisation (week 0) to end-of-trial (up to 61 months or more)

Months

Change in body weightFrom randomisation (week 0) to 2 years

Kilograms

Number of severe hypoglycaemic episodesFrom randomisation (week 0) to end-of-trial (up to 61 months or more)

Number of events

Time to first occurrence of an expanded MACE composite endpoint consisting of: CV death/non-fatal myocardial infarction/ non-fatal stroke/coronary revascularisation/unstable angina requiring hospitalisationFrom randomisation (week 0) to end-of-trial (up to 61 months or more)

Months

Time to occurrence of all-cause deathFrom randomisation (week 0) to end-of-trial (up to 61 months or more)

Months

Time to first occurrence of urgent heart failure visitFrom randomisation (week 0) to end-of-trial (up to 61 months or more)

Months

Time to first occurrence of onset of persistent 50% or more reduction in eGFRFrom randomisation (week 0) to end-of-trial (up to 61 months or more)

Months

Change in glycosylated haemoglobin (HbA1c)From randomisation (week 0) to 2 years

Percent points

Time to first occurrence of a severe hypoglycaemic episodeFrom randomisation (week 0) to end-of-trial (up to 61 months or more)

Months

Time to occurrence of renal deathFrom randomisation (week 0) to end-of-trial (up to 61 months or more)

Months

Trial Locations

Locations (464)

Healthscan Clinical Trials,LLC.

🇺🇸

Montgomery, Alabama, United States

Medical Investigations, Inc.

🇺🇸

Little Rock, Arkansas, United States

Unity Health-Searcy Medical Center

🇺🇸

Searcy, Arkansas, United States

B&K Medical Research Center

🇺🇸

Fresno, California, United States

Scripps Whittier Diabetes Inst

🇺🇸

La Jolla, California, United States

Diabetes & Endocrine Associates

🇺🇸

La Mesa, California, United States

First Valley Medical Group

🇺🇸

Lancaster, California, United States

Pacific Clinical Studies

🇺🇸

Los Alamitos, California, United States

Facey Medical Foundation

🇺🇸

Mission Hills, California, United States

Monterey Endocrine & Diabetes Institute, Inc

🇺🇸

Monterey, California, United States

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Healthscan Clinical Trials,LLC.
🇺🇸Montgomery, Alabama, United States

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