CTRI

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CTRI Number

CTRI/2018/10/016193 [Registered on: 29/10/2018] Trial Registered Prospectively

Last Modified On:

12/01/2024

Post Graduate Thesis

Type of Trial

Interventional

Type of Study

Drug

Study Design

Randomized, Parallel Group, Placebo Controlled Trial

Public Title of Study

A randomised, double-blind, parallel group, placebo-controlled trial comparing semaglutide 2.4 mg with semaglutide placebo both administered s.c. once-weekly in subjects with established CV disease and overweight or obesity

Scientific Title of Study

Semaglutide effects on cardiovascular outcomes in people with overweight or obesity

Trial Acronym

Secondary IDs if Any
Modification(s)

Secondary ID	Identifier
EX9536-4388, Version 7.0 Dated 09-Feb-2022	Protocol Number
U1111-1200-5564	UTN

Details of Principal Investigator or overall Trial Coordinator (multi-center study)

Name	Dr Upendra Kaul
Designation	Chairman -Batra Heart Centre
Affiliation	Batra Hospital and Medical Reaserch Centre 1
Address	Batra Hospital and Medical Reaserch Centre 1, Tughlakabad Institutional Area Mehrauli Badarpur Road, Vayusenabad,New Delhi New Delhi DELHI 110062 India
Phone	01129958747
Fax	01129956255
Email	kaul.upendra@gmail.com

Details of Contact Person
Scientific Query
Modification(s)

Name	Maya Sharma
Designation	Vice President - Clinical, Medical, Regulatory & Pharmacovigilance
Affiliation	Novo Nordisk India Private Ltd.
Address	NXT Tower-2, Floor 1 & 2, Embassy Manyata Business Park, Nagavara Village, Kasaba Hobli, Bangalore-560 045 Karnataka, India Bangalore KARNATAKA 560045 India
Phone	9911497869
Fax
Email	yrms@novonordisk.com

Details of Contact Person
Public Query
Modification(s)

Name	Maya Sharma
Designation	Senior Director - CMR
Affiliation	Novo Nordisk India Private Ltd.
Address	Novo Nordisk India Private Ltd. Plot No.32, 47 - 50, EPIP Area, Whitefield. Bangalore KARNATAKA 560066 India
Phone	09911497869
Fax	08041123518
Email	yrms@novonordisk.com

Source of Monetary or Material Support

Novo Nordisk India Private Ltd, Plot No.32, 47 - 50, EPIP Area, Whitefield, Bangalore - 560 066, India

Primary Sponsor

Name	Novo Nordisk AS
Address	Novo AllÃ©, 2880 Bagsvaerd Denmark
Type of Sponsor	Pharmaceutical industry-Global

Details of Secondary Sponsor

Name	Address
NIL	NIL

Countries of Recruitment

Argentina
Australia
Austria
Belgium
Brazil
Bulgaria
Canada
Colombia
Croatia
Czech Republic
Denmark
Finland
France
Germany
Greece
Hungary
India
Ireland
Israel
Italy
Japan
Latvia
Malaysia
Mexico
Netherlands
Norway
Poland
Portugal
Romania
Russian Federation
Serbia
South Africa
Spain
Sweden
Taiwan
Thailand
Turkey
Ukraine
United Kingdom
United States of America
Algeria

Sites of Study
Modification(s)

No of Sites = 35
Name of Principal Investigator	Name of Site	Site Address	Phone/Fax/Email
Dr Ambuj Roy	All India Institute of Medical Sciences	Department of Cardiology, Cardio Thoracic Science Centre, Ansari Nagar, New Delhi, 110029 New Delhi DELHI	01126593861 01126588663 drambujroy@gmail.com
Dr Tejas Patel	Apex Heart Institute	Department of Cardiology , Block: G K Mondeal Business Park, Near gurudwara SG Highway, Ahmedabad-380054 Ahmadabad GUJARAT	9824030576 7926842288 tejaspatel@apexheart.in
Dr Jaspal Singh Arneja	Arneja Heart and Multi Speciality Hospital	123 Ramdaspeth Nagpur-440010 Nagpur MAHARASHTRA	9823056562 jaspalarneja_200@yahoo.com
Dr Dhiman Kahali	B M Birla Heart Research Center	Department of Cardiology, 1/1 National Library Avenue, Kolkata 700027, West Bengal, India Kolkata 700027 Kolkata WEST BENGAL	9830048563 3324567000 dhiman.kahali@gmail.com
Dr Upendra Kaul	Batra Hospital and Medical Reaserch Centre	Department of cardiology, 1, Tughlakabad Institutional Area Mehrauli Badarpur Road, Vayusenabad,New Delhi New Delhi DELHI	9811150518 01129956255 kaul.upendra@gmail.com
Dr Satbir Singh	BLK Center for cardiac Sciences Dr B .L Kapur Memorial Hospital	Pusa Road , New Delhi 110005 New Delhi DELHI	9717456667 drsatbar9717456667@gmail.com
Dr Nihal Thomas	Christian Medical College	Department of Cardiology, 810, Vellore-632004 Vellore TAMIL NADU	4162282694 4164200854 nihal_thomas@yahoo.com
Dr Ajay Naik	CIMS hospital	Department of cardiology,Off Science City Road, Panchamrut Bunglows II, Sola, Ahmedabad Gujarat 380060 Ahmadabad GUJARAT	9825082666 ajay.naik@cims.me
Dr Gurpreet Singh Wander	Dayanand Medical College and Hospital	Unit Hero DMC Heart Institute, Tagore Nagar, Ludhiana-141001, Punjab, India. Ludhiana PUNJAB	9815545316 drgswander@yahoo.com
Dr P Ramesh Babu	Dr. Ramesh Cardiac and Multispeciality Hospital P Ltd.	Clinical Research Room,Ring Road, Near ITC College, Vijaywada-520008 Krishna ANDHRA PRADESH	9848448999 Dr_rameshbabu_p@yahoo.com
Dr Arun Kumar Chopra	Fortis Escorts Hospital	Majitha Verka Bypass Road, Amritsar-143004, Punjab India Amritsar PUNJAB	9815554800 akchopra1@rediffmail.com
Dr Rajpal Abhaichand	G Kuppuswamy Naidu Memorial Hospital	Bost Box No. 6327, Nethaji road, Pappanaick en palayam, Coimbatore-641037, Tamilnadu, India. Coimbatore TAMIL NADU	9443272172 rka.trials@gmail.com
Dr M S Hiremath	Grant Medical Foundation Ruby Hall Clinic	Department of Cardiology, 40, Sassoon Road, Pune 411001. Pune MAHARASHTRA	9822055440 02066455376 hiremath.shirish@gmail.com
Dr Johann Christopher	Gurunanak CARE Hospital	Department of Cardiology, 1-4-908/7/1, Bakaram Musheerabad, Hyderabad Hyderabad Telangana 500020 Hyderabad TELANGANA	9701445011 johann1403@gmail.com
Dr Brian Pinto	Holy Family Hospital	6th Floor, Research department for cardiology, St. Andrewâ€™s Road, Bandra, Maharashtra â€“ 400050 Mumbai MAHARASHTRA	9820054913 bpiifc@gmail.com
Dr Prafulla G kerkar	K E M hospital & Seth G S Medical College	Department of Cardiology, 4 th floor, CVTC Building, Acharya Donde Marg, Parel , Mumbai 400012. Mumbai MAHARASHTRA	02224107636 912224116732 prafullakerkar@rediffmail.com
Dr Ajit R Bhagwat	Kamalnayan Bajaj Hospital	Department of cardiology, Gut no. 43, Bajaj Marg Beed Bypass Road, Satara Parisar, Aurangabad, Maharashtra-431010 Aurangabad MAHARASHTRA	9822050817 drajitbhagwat@gmail.com
Dr Padma Kumar	Kasturba Medical College and Hospital	Department of Cardiology,Udyavara, Manipal, Udupi-576104 Udupi KARNATAKA	8202571201 8202571934 padmakumar69@yahoo.com
Dr Rishi Sethi	King Georgeâ€™s Medical University	Department of Cardiology, Shah Mina Road, Chowk, Lucknow-226003 Lucknow UTTAR PRADESH	915222257540 915222258948 drrishisethi1@gmail.com
Dr Zohaib Shaikh	Lokmanya Thilak Municipal Medical College & General Hospital	Lokmanya Tilak Municipal Medical College and General Hospital Dr Babasaheb Ambedkar Rd RB2 Central Railway Quarters Sion West Sion Mumbai Maharashtra 400022 Mumbai MAHARASHTRA	9869286469 drzohaibshaikh@gmail.com
Dr Sandeep Garg	Maulana Azad Medical College	Department of Medicine Room Number 120, Department of Medicine, B L Taneja Block, New Delhi, 110002. New Delhi DELHI	9968604280 0112323-5452 drsandeepgargmamc@gmail.com
Dr Sanjay Mittal	Medanta- The Medicity Hospital	Department of cardiology, Sector- 38, Gurgaon, Haryana 122001 Gurgaon HARYANA	9910044477 Sanjay.Mittal@Medanta.org
Dr Kannan J	Narayana Institute of Cardiac sciences	Department of Clinical Research Cardiology, Narayana Health City, Taluk, Anekal, 258/A, Hosur Road, Bommasandra Industrial Area, Bengaluru, Karnataka â€“ 560099 Bangalore KARNATAKA	9845683474 8071222671 drkannanu@yahoo.co.in
Dr Piyush Desai Harshadrai	Nirmal Hospital Private Limited	Diabetes and Endocrinology depy,Ring Road, Surat, Gujarat- 395002 Surat GUJARAT	9825144453 drpiyushdesai@gmail.com
Dr Krishna Mala Konda Reddy P	Osmania Medical College and General Hospital,	Department of cardiology, Afzalgunj Hyderabad Telangana 500012 Hyderabad TELANGANA	9848015098 drkmkreddyp@yahoo.com
Dr Atul Abhyankar	Shri B D Mehta Mahavir Heart Institute	Department of Cardiology , OPD No. 1, Cardiology department Athwagate, ring road Surat Gujarat 395001 Surat GUJARAT	9825145738 heartfirst.surat@gmail.com
Dr Mahesh Fulwani	Shrikrishna Hrudayala and Critical Care Centre	Congress Nagar Square Tikekar Road Dhantoli 440012 Nagpur MAHARASHTRA	7122444434 drmaheshfulwani@gmail.com
Dr Jitendra Pal Singh Sawhney	Sir Ganga Ram Hospital	Department of cardiology, Sir Gnaga Ram Hospital, SGRH Marg, Rajinder Nagar, New Delhi-110060 New Delhi DELHI	09810059773 01166173891 jpssawhney@yahoo.com
Dr D K Agarwal	SP Medical College & A.G.Hospital Bikaner	Research cell, B Block, Department of Cardiology,Rajasthan-334003 Bikaner RAJASTHAN	9829217899 research_spmc@yahoo.com
Dr Manjunath Nanjappa	Sri Jayadeva Institute of Cardiovascular sciences and Research	Department of Cardiology, Jayanagar 9th Block, Bannerghatta Main Road, Bangalore 560069. Bangalore KARNATAKA	08022977422 8022977395 drcnmanjunath@gmail.com
Dr Kiron Varghese	St. Johnâ€™s Medical College and Hospital	Sarjapur Main Rd, Koramangala, Bengaluru, Karnataka 560034. Bangalore KARNATAKA	9845167912 drkiron@hotmail.com
Dr Manoj Kumar Shah	The Madras Medical Mission	Department of Cardiology, 4-A, Dr. J.J.Nagar, Mogappair, Chennai-600037 Chennai TAMIL NADU	4426565974 clireco@mmm.org.in
Dr Devang M Desai	Unicare Heart Institute and Research Centre	1st floor OPD ,52,Canal Road ,Ambanagar,395001 Surat GUJARAT	9825117900 devangdesai2@yahoo.com
Dr Sandeep Bansal	Vardhaman Mahavir Medical College Safdarjung Hospital	VMMC Safdarjung Hospital New Delhi 110029 New Delhi DELHI	9810543368 drsbansal2000@yahoo.com
Dr Vinod Vijan	Vijan Cardiac & Critical Care Centre	College Rd, Nashik, Maharashtra- 42200 Nashik MAHARASHTRA	9822025353 vmvijan@hotmail.com

Details of Ethics Committee
Modification(s)

No of Ethics Committees= 35
Name of Committee	Approval Status
Arnejas Institutional Ethics Committee	Approved
Care Hospital, Institutional Ethics Committee	Approved
Drugs Trial Ethics committee	Approved
Ethics Committee of Care Institute of Medical Sciences	Approved
Ethics Committee Apex Heart Institute	Submittted/Under Review
Ethics Committee Kamalnayan Bajaj Hospital	Approved
Ethics Coommittee SP Medical College and AG Hospitals	Approved
Institutional Ethics Committe The Madras Medical Mission	Approved
Institutional Ethics Committe, AIIMS	Approved
Institutional Ethics Committee	Submittted/Under Review
Institutional Ethics Committee (IEC)-I, Seth G. S. Medical college and KEM Hospital	Approved
Institutional Ethics Committee Dr. Ramesh Cardiac and Multispeciality Hospital P Ltd	Approved
Institutional Ethics Committee G Kuppuswamy Naidu Memorial Hospital	Approved
Institutional Ethics Committee human research	Approved
Institutional Ethics Committee, Dr B L Kapur Memorial Hospital	Approved
Institutional Ethics Committee, Fortis Escorts Hospital	Approved
Institutional Ethics Committee, MAMC	Approved
Institutional Ethics Committee, Osmania Medical College	Approved
Institutional Ethics Committee, Poona medical research Foundation	Approved
Institutional Ethics Committee, St Jonhs Medical College	Approved
Institutional Ethics Committee, Vardhaman Mahavir Medical College & Safdarjung Hospital	Approved
Institutional Ethics Committee-KGMU	Approved
Institutional Review Board -Silver	Submittted/Under Review
MAHE Ethics Committee	Approved
Medanta Institutional ethics Committee	Approved
Narayana Health Medical Ethics Committee	Approved
Nirmal Hospital Pvt Ltd Ethics Committee	Approved
Sceintific Research And Ethical Review Committee	Approved
Shri B D Mehta Mahavir Heart Institute Ethics Committee	Approved
Sir gangaram Hospital Ethics Committee	Approved
Sri Jayadeva Institute Ethics Committee	Approved
The Bandra Holy Family Medical Research Society	Approved
Unity Hospital Ethics Committee	Approved
Vijan Hospital Ethics Committee	Approved
Virtuous Institutional Medical Research Ethics Committee	Approved

Regulatory Clearance Status from DCGI

Status

Approved/Obtained

Health Condition / Problems Studied
Modification(s)

Health Type	Condition
Patients	(1) ICD-10 Condition: E66\|\|Overweight and obesity, (2) ICD-10 Condition: I30-I52\|\|Other forms of heart disease, (3) ICD-10 Condition: E66\|\|Overweight and obesity,

Intervention / Comparator Agent

Type	Name	Details
Comparator Agent	Placebo	Dose: Subjects will be initiated at a once-weekly dose of 0.24 mg s.c. and follow a fixed-dose escalation regimen, with dose increases every 4 weeks (to doses of 0.5, 1.0, 1.7 and 2.4 mg/week), until the target dose is reached after 16 weeks.
Intervention	Semaglutide	Dose: Subjects will be initiated at a once-weekly dose of 0.24 mg s.c. and follow a fixed-dose escalation regimen, with dose increases every 4 weeks (to doses of 0.5, 1.0, 1.7 and 2.4 mg/week), until the target dose is reached after 16 weeks.

Inclusion Criteria

Age From	45.00 Year(s)
Age To	99.00 Year(s)
Gender	Both
Details	1. 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 2. Male or female, age more than or equal to 45 years at the time of signing informed consent 3. Body mass index more than or equal to 27 kg per m2. 4. Have established CV disease as evidenced by at least one of the following: a. prior myocardial infarction b. prior stroke (ischemic or hemorrhagic stroke) c. symptomatic peripheral arterial disease, as evidenced by intermittent claudication with ankle-brachial index less than 0.85 at rest , or peripheral arterialrevascularization procedure, or amputation due to atherosclerotic disease.

ExclusionCriteria

Details

Cardiovascular-related:
1. 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
2. Planned coronary, carotid or peripheral artery revascularisation known on the day of screening
3. Presently classified as being in New York Heart Association (NYHA) Class IV heart failure
Glycaemia-related:
4. HbA1c more than or equal to48 mmolpermol -6.5 percent as measured by the central laboratory at screening
5. History of type 1 or type 2 diabetes -history of gestational diabetes is allowed.
6. Treatment with glucose-lowering agents within 90 days before screening
7. Treatment with any GLP-1 RA within 90 days before screening
General safety:
8. History or presence of chronic pancreatitis
9. Presence of acute pancreatitis within the past 180 days prior to the day of screening
10. Personal or first degree relatives history of multiple endocrine neoplasia type 2 or medullary thyroid carcinoma
11. End stage renal disease or chronic or intermittent haemodialysis or peritoneal dialysis
12. 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
13. Severe psychiatric disorder which in the investigatorâ€™s opinion could compromise compliance with the protocol
14. Known or suspected hypersensitivity to trial products or related products
15. Previous participation in this trial. Participation is defined as randomisation
16. Receipt of any investigational medicinal product within 30 days before screening
17. 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
18. Any disorder, unwillingness or inability, which in the investigatorâ€™s opinion, might jeopardise the subjectâ€™s safety or compliance with the protocol

Method of Generating Random Sequence

Computer generated randomization

Method of Concealment

Centralized

Blinding/Masking

Participant, Investigator and Outcome Assessor Blinded

Primary Outcome

Outcome	TimePoints
The primary endpoint is time from randomisation to first occurrence of a composite endpoint consisting of: CV death, non-fatal myocardial infarction, or non-fatal stroke	upto 59 months

Secondary Outcome

Outcome	TimePoints
Time from randomisation to: CV death All-cause death	upto 59 months
Time from randomisation to first occurrence of: An expanded composite CV endpoint consisting of: CV death, non-fatal myocardial infarction, non-fatal stroke, coronary revascularisation or unstable angina requiring hospitalisation A composite heart failure endpoint consisting of: heart failure hospitalisation, urgent heart failure visit or CV death A composite endpoint consisting of: all-cause death, non-fatal myocardial infarction, or nonfatal stroke	upto 59 months
Time from randomisation to first occurrence of: Non-fatal myocardial infarction Non-fatal stroke Coronary revascularisation Unstable angina requiring hospitalisation Heart failure hospitalisation or urgent heart failure visit HbA1c more than or equal to 48 mmol per mol (6.5 percent) A 5-component composite nephropathy endpoint	upto 59 months
Change from randomisation to year 2 (visit14) in: Systolic blood pressure (mmHg) Diastolic blood pressure (mmHg) Pulse (bpm) High sensitivity C-Reactive Protein (hsCRP) (mg/L) Lipids (mg/dL) Total cholesterol High density lipoprotein (HDL) cholesterol Low density lipoprotein (LDL) cholesterol Triglycerides Body weight (%) Waist circumference (cm) Patient reported outcomes HbA1c (%, mmol /mol) change from screening (visit 1) to year 2 (visit 14)	upto 59 months

Target Sample Size
Modification(s)

Total Sample Size="17500"
Sample Size from India="600"
Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials"
Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials"

Phase of Trial

Phase 3

Date of First Enrollment (India)

07/12/2018

Date of Study Completion (India)

Applicable only for Completed/Terminated trials

Date of First Enrollment (Global)

24/10/2018

Date of Study Completion (Global)

Applicable only for Completed/Terminated trials

Estimated Duration of Trial

Years="4"
Months="11"
Days="0"

Recruitment Status of Trial (Global)
Modification(s)

Closed to Recruitment of Participants

Recruitment Status of Trial (India)

Closed to Recruitment of Participants

Publication Details
Modification(s)

Published

Individual Participant Data (IPD) Sharing Statement

Will individual participant data (IPD) be shared publicly (including data dictionaries)?

Brief Summary

This is a randomised, double-blind, parallel group, placebo-controlled trial comparing semaglutide 2.4 mg with semaglutide placebo both administered s.c. once-weekly in subjects with established CV disease and overweight or obesity. Subjects will be randomised in a 1:1 ratio to receive either semaglutide 2.4 mg or semaglutide placebo as an adjunct to standard-of-care. The trial is event driven with trial closure being performed when the targeted number of primary endpoint events has been reached. An independent Data Monitoring Committee (DMC) will oversee subject safety and may recommend stopping the trial early. With the assumed event rate and a recruitment period of 28 months, the estimated trial duration will be 59 months from start of randomisation to end of follow-up of the last subject,including 28 months of recruitment and 7 weeks of follow-up. Estimated trial duration for an individual subject is from 31 to 59 months.