Novo Nordisk India Private Limited, Nxt Tower - 2, Floor 1 & 2
Embassy Manyata Business Park,
Nagavara Village, Kasaba Hobli,
Bangalore - 560045. India
Argentina Austria Belgium Brazil Canada China Colombia Croatia Czech Republic Denmark France Germany Hong Kong India Israel Italy Japan Malaysia Mexico Netherlands Republic of Korea Romania Russian Federation Serbia Slovakia South Africa Spain Taiwan Thailand Turkey Ukraine United Kingdom United States of America
Department Of Endocrinology IPGMER SSKM Hospital Ronald Ross Building 4th floor Room no8 244AJC Bose Road Kolkata700020 Kolkata WEST BENGAL
9674625823
drsujoyghosh2000@gmail.com
Dr Nikhil Tandon
All India Institute of Medical Sciences
All India Institute of Medical Sciences, Room no.311, Biotechnology Block, Ansari Nagar, New Delhi-110029 New Delhi DELHI
9818211663
nikhil_tandon@hotmail.com
Dr Tirthankar Chaudhury
Apollo Gleneagles Hospitals, Kolkata
Apollo Gleneagles Hospitals, Kolkata. 58, Canal Circular Road Kolkata- 700054 Kolkata WEST BENGAL
9831322394
tirthankarc05@gmail.com
Dr Nikhil Bhagwat
B Y L Nair Hospital
Department of Endocrinology, Dr. A. L. Nair Road, Mumbai, Maharashtra 400008, India Mumbai MAHARASHTRA
9820238399
bhagwatnik@yahoo.co.in
Dr Manoj Chawla
BSES Municipal General Hospital
BSES Municipal General Hospital, S.V.Road, Opposite Railway Station, Andheri (W), Mumbai- 400058 Mumbai MAHARASHTRA
9820002333
drmanojchawla@yahoo.com
Dr Bipin Sethi
CARE Outpatient Centre
Care Out Patient Centre, Door No. 8-2-620/A, Babu Khan Chambers, Road No. 10, Banjara Hills, Hyderabad - 500034 Hyderabad TELANGANA
9848021482
sethibipin54@gmail.com
Dr Unnikrishnan AG
Chellaram Hospital – Diabetes care & Multispeciality
Lalani Quantum, Pune – Bangalore National Highway no. 4, opp.calsoft building, Bavdhan (Budruk), Pune, Maharashtra – 411021. Pune MAHARASHTRA
9689287337
uagcdi@cdi.org.in
Dr Nihal Thomas
Christian Medical College
810, Department of Endocrinology Diabetes & Metabolism Christian Medical College, Vellore -632004, Tamilnadu, India Vellore TAMIL NADU
9843111996
nihal_thomas@yahoo.com
Dr Jubbin Jagan Jacob
Christian Medical College & Hospital, Ludhiana
Christian Medical College and Hospital Endocrine and Diabetes Unit, Brown Road, Ludhiana – 141008 Ludhiana PUNJAB
9915281219
endocrinecmc@gmail.com
Dr Saurabh Arora
Dayanand Medical College & Hospital
3rd Floor, Department of Endocrinology (Reseacrh), Dayanand Medical College and Hospital, Civil Lines, Tagore Nagar, Ludhiana - 141001 Ludhiana PUNJAB
91-9814077536
saurabharora3084@gmail.com
Dr Surendra Kumar Sharma
Diabetes Thyroid & Endocrine Centre
Diabetes Thyroid & Endocrine Centre, A-1,Madrampura, Ajmer Road, Near 4no. ESI Hospital ,Sodala,Jaipur-302006 (Rajasthan) Jaipur RAJASTHAN
9829010233
sksharmacr@gmail.com
Dr Banshi Saboo
Dr. Jivraj Mehta Smarak Health Foundation Bakerti Medical Research Centre
Dr. Jivraj Mehta Smarak Health Foundation Bakerti Medical Research Centre, "Rutubhai Adani Arogyadham", Dr. Jivraj Mehta Marg,
Ahmedabad 380007
Ahmadabad GUJARAT
9824047676
banshisaboo@hotmail.com
Dr Manash P Baruah
Excel Care Hospitals
Room no- 120, 1st floor OPD Block,
Endocrinology & Diabetology Department
Excel Care Hospitals
Near Ganesh Mandir, Boragaon, NH-37
Guwahati, Assam- 781033
Kamrup ASSAM
9435018344
manashb2@gmail.com
Dr KP Singh
Fortis healthcare Limited
Room no 603 Basement, Biomedical -Engineering Department Sector 62, Phase VIII, Mohali -160062 Chandigarh CHANDIGARH
9815311711
drkp1292@gmail.com
Dr Bipinkumar Daxini
Fortis Hospital
Department of Endocrinology, Diabetes & Metabolism, Mulund Goregaon Link Rd, Nahur West, Industrial Area, Mulund West, Mumbai, Maharashtra 400078, India Mumbai MAHARASHTRA
9820709756
bipindaxini@gmail.com
Dr D Vijay Sekhar Reddy
Gandhi Medical College and Hospital
Department of Endocrinology, 3rd floor, Gandhi Medical College and Hospital, Musheerabad, Secunderabad, Telengana 500003 Hyderabad TELANGANA
9849172161
drdvsreddyendo@Yahoo.com
Dr Shameer Vadekkandiyil
Govt. Medical College
Calicut medical College, Department of General Medicine, P.O. Calicut - 673008, Kerala Kozhikode KERALA
Inamdar Multispeciality Hospital, Inamdar Hospital building s No. 15, Fatima Nagar, Pune, Maharashtra 411040 Pune MAHARASHTRA
9823141402
ydkresearch10@gmail.com
Dr Jothydev Kesavadev
Jothydevs Diabetes Research Centre
Jothydevs Diabetes Research Centre
JDC Junction, Konkalam Road, Mudavanmugal, Poojappura P.O, Trivandrum, Kerala 695032
Thiruvananthapuram KERALA
9895040055
jothydev@gmail.com
Dr Alok Kanungo
Kanungo Institute of Diabetes Specialities
Kanungo Institute of Diabetes Specialities, Plot 1120, Dumduma, Bhubaneshwar- 751019, Odisha Khordha ORISSA
9437055740
kanungokids@gmail.com
Dr Girithara Gopalakrishnan Jayaram Naidu
KG hospital
KG hospital and post graduate medical institute, No.5 Govt. Arts College Road, Coimbatore – 641018, Tamilnadu Coimbatore TAMIL NADU
9443170088
drgirimd@yahoo.com
Dr Paturi Vishnupriya Rao
Kumudini Devi Diabetes Research Center, Ramdevrao Hospital
Kumudini Devi Diabetes Research Center, Ramdevrao Hospital (A Unit of Sivananda Rehabilitation Home), Kukatpally, Hyderabad, Telangana, India. 500072 Hyderabad TELANGANA
9885051110
raopaturi@gmail.com
Dr Anupam Prakash
Lady Hardinge Medical College & asso. hospitals
Room No. 1014, Dept. of Medicine, Lady Hardinge Medical College & asso. hospitals, Panchkuin Road,New Delhi- 110001 New Delhi DELHI
8588885305
prakashanupam@hotmail.com
Dr L Sreenivasa Murthy
Life Care Hospital & Research Centre
Life Care Hospital & Research Centre
M.L.N Enclave, 16th ‘E’ Cross Road, 8th Main ‘D’ Block, Next to Corporation Bank, Sahakarnaga, Bangalore-560092
Bangalore KARNATAKA
9448051046
drlsm@lcrc.in
Dr Suryanarayana Murthy
M S Ramaiah Clinical Research Center
1st Floor M S Ramaiah Advance Learning Centre, Gnanagangothri campus, M S Ramaiah Nagar, MSRIT Post, Bangalore-560054 Bangalore KARNATAKA
9742971563
dr.suryanarayana@gmail.com
Dr V Mohan
Madras Diabetes Research Foundation
Madras Diabetes Research Foundation, #4 Conran Smith Road, Gopalapuram, Chennai 600 086, India Chennai TAMIL NADU
044-43968888
drmohans@diabetes.ind.in
Dr Rakesh Kumar Sahay
Osmania General Hospital
Osmania General Hospital,Department of Endocrinology, Osmania Medical College & Osmania General Hospital, Afzalgunj, Hyderabad – 500 012, Telangana, India. Hyderabad TELANGANA
9849597507
sahayrk@gmail.com
Dr Manoj Chadha
P D Hinduja Hospital
Department of Endocrinology SVS Rd, Mahim West, Mumbai, Maharashtra 400016 India Mumbai MAHARASHTRA
9821548346
mchadha59@gmail.com
Dr Jasminder Singh
Pandit Bhagwat Dayal Sharma Post Graduate Institute of Medical Sciences
Department of Endocrinology, Ward No 9, Pandit Bhagwat Dayal Sharma Post-Graduate Institute of Medical Sciences, Rohtak-124001, Haryana, India Rohtak HARYANA
09813140750
jasminder.singh20@gmail.com
Dr P Sudhakar Reddy
Sunshine Hospital
1-7-201-205, P G ROAD, BESIDE PARADISE HOTEL, Secunderabad-500003 Hyderabad TELANGANA
9848449812
drsudhakarreddypendyala@gmail.com
Dr Sunil M Jain
TOTALL Diabetes Hormone Institute
TOTALL Diabetes Hormone Institute
BCM Health Island PU-4,Scheme No. 54
Near Bomaby Hospital,Behind Prestige Institute of Management
Indore 452010
Indore MADHYA PRADESH
IPGME&R Research oversight committee , Institute of post graduate medical education and research
Approved
KIDS Ethics Committee, Bhubaneswar
Approved
Life Care Hospital Institutional Review Board
Approved
Sunshine Institutional Ethics Committee
Approved
The Ethics Committee of M S Ramaiah Medical College and Hospitals
Approved
The Institutional Ethics Committee, Fortis hospital, Mohali
Approved
Regulatory Clearance Status from DCGI
Status
Approved/Obtained
Health Condition / Problems Studied
Health Type
Condition
Patients
(1) ICD-10 Condition: E116||Type 2 diabetes mellitus with other specified complications,
Intervention / Comparator Agent
Type
Name
Details
Intervention
Oral Semaglutide
Drug: Semaglutide
Increasing doses (3 mg/7 mg/14 mg) of semaglutide .One tablet daily for 3.5 to 5 years. tablets to be taken with water at the same time every morning in a fasting state
Comparator Agent
Placebo
Drug: Placebo
Placebo tablets One tablet daily for 3.5 to 5 years to be taken with water at the same time every morning in a fasting state
1. Male or female, age ≥50 years at the time of signing informed consent.2. Diagnosed with type 2 diabetes mellitus.3. HbA1c 6.5% - 10.0% (47 - 86 mmol/mol) (both inclusive).4. 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% stenosis in coronary artery documented by cardiac catheteri-sation or CTcoronary 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 foll-owing:i.Prior stroke. ii. Prior carotid artery revascularisation procedure.iii. ≥50% stenosis in carotid artery documented by X-ray angiography MR angiography, CT angiography or Doppler ultra-sound c) Symptomatic peripheral artery disease (PAD) defined as at least one of the following: i. Intermittent claudication with an Ankle-brachial index (ABI) < 0.85 at rest.ii. Intermitt-ent claudication with a ≥50% stenosis in periphe-ral artery (excluding carotid) documented by X-ray angiography,MR angiography,CT angiography or Doppler ultrasound.iii. Prior peripheral artery (excluding carotid) revascularization procedureiv. 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 < 60 mL/min/1.73m2b.
ExclusionCriteria
Details
1. Known or suspected hypersensitivity to trial product or related products.
2. Previous participation in this trial. Participation is defined as randomisation.
3. 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.
4. Participation in any clinical trial of an approved or non-approved investigational medicinal
product within 30 days before screening.
5. Any disorder, which in the investigator’s opinion might jeopardise patient’s safety or
compliance with the protocol.
6. Any of the following - myocardial infarction, stroke, hospitalisation for unstable angina pectoris
or transient ischaemic attack (TIA) within the past 60 days prior to the day of screening
7. Planned coronary, carotid or peripheral artery revascularisation.
8. Heart failure presently classified as being in New York Heart Association (NYHA) Class IV.
9. Treatment with any GLP-1 receptor agonist (RA) within 30 days before screening.
10. Uncontrolled and potentially unstable diabetic retinopathy or maculopathy. Verified by a fundus
examination performed within the past 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.
11. Presence or history of malignant neoplasm within 5 years prior to the day of screening. Basal
and squamous cell skin cancer and any carcinoma in-situ is allowed.
12. Personal or first degree relative(s) history of MEN2 or MTC.
13. End stage renal disease or chronic or intermittent haemodialysis or peritoneal dialysis.
14. History of major surgical procedures involving the stomach or small intestine potentially
affecting absorption of drugs and or nutrients, as judged by the investigator.
Method of Generating Random Sequence
Computer generated randomization
Method of Concealment
Centralized
Blinding/Masking
Participant, Investigator and Outcome Assessor Blinded
Primary Outcome
Outcome
TimePoints
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 stroke
From randomisation (week 0) to end-of-trial (up to 61 months or more) (trial is event driven) ]
Months
1.Time to first occurrence of a composite endpoint consisting of: CV death/renal death/onset of persistent 50 percent 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 per min per 1.73 meter square per initiation of chronic renal replacement therapy (dialysis or kidney transplantation).
Time Frame: From randomisation (week 0) to end-of-trial (up to 61 months or more) ]
Months
2. Time to occurrence of CV death
3. Time to first occurrence of major adverse limb events (MALE), a composite endpoint consisting of: acute limb ischemia hospitalisation/chronic limb ischemia hospitalisation
4.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 hospitalisation.
Time Frame: From randomisation (week 0) to end-of-trial (up to 61 months or more) ]
Months
5. Time to first occurrence of a composite heart failure endpoint consisting of: CV death/heart failure requiring hospitalisation/urgent heart failure visit
Time Frame: From randomisation (week 0) to end-of-trial (up to 61 months or more) ]
Months
6.Time to first occurrence of a composite CKD endpoint. Time to first occurrence of a composite CKD endpoint consisting of: renal death/onset of persistent 50 percent or more reduction in eGFR (CKD-EPI)/onset of persistent eGFR (CKD-EPI) below 15 mL per min per 1.73 meter square per initiation of chronic renal replacement therapy (dialysis or kidney transplantation).
Time Frame: From randomisation (week 0) to end-of-trial (up to 61 months or more) ]
Months
7. Time to occurrence of all-cause death
8. Time to first occurrence of non-fatal myocardial infarction (MI)
9. Time to first occurrence of non-fatal stroke
10. Time to first occurrence of heart failure requiring hospitalisation
11. Time to first occurrence of urgent heart failure visit
Time Frame: From randomisation (week 0) to end-of-trial (up to 61 months or more)
12. Time to first occurrence of coronary revascularisation
13. Time to first occurrence of unstable angina requiring hospitalisation
14. Time to occurrence of renal death
15.Time to first occurrence of onset of persistent 50percent or more reduction in eGFR
Time Frame: From randomisation (week 0) to end-of-trial (up to 61 months or more) ]
Months
16. Time to first occurrence of onset of persistent eGFR (CKD-EPI) below 15 mL per min per 1.73 meter square
17. Time to first occurrence of initiation of chronic renal replacement therapy (dialysis or kidney transplantation)
18.Time to first occurrence of a composite endpoint consisting of: all-cause death/non-fatal myocardial infarction/non-fatal stroke
19. Time to first occurrence of acute limb ischemia
20. Time to first occurrence of chronic limb ischemia
Time Frame: From randomisation (week 0) to end-of-trial (up to 61 months or more) ]
Months
21.Annual rate of change in eGFR (CKD-EPI) (total eGFR slope)
Time Frame: From randomisation (week 0) to end-of-trial (up to 61 months or more) ]
ml per min per 1.73 meter square per year
22.Change in glycosylated haemoglobin (HbA1c)
Time Frame: From randomisation (week 0) to 2 years ]
Percent points
23.Change in body weight
Time Frame: From randomisation (week 0) to 2 years ]
Kilograms
24. Number of severe hypoglycaemic episodes
Time Frame: From randomisation (week 0) to end-of-trial (up to 61 months or more) ]
Number of events
25. Time to first occurrence of a severe hypoglycaemic episode
Time Frame: From randomisation (week 0) to end-of-trial (up to 61 months or more) ]
Months
Total Sample Size="9642" Sample Size from India="900" Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials" Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials"
Individual Participant Data (IPD) Sharing Statement
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Response - NO
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.