| CTRI Number |
CTRI/2017/08/009207 [Registered on: 01/08/2017] Trial Registered Prospectively |
| Last Modified On: |
01/09/2021 |
| Post Graduate Thesis |
No |
| Type of Trial |
Interventional |
|
Type of Study
|
Drug |
| Study Design |
Randomized, Parallel Group, Placebo Controlled Trial |
|
Public Title of Study
|
A clinical trial to determine if the test drug (Dapagliflozin) is better that placebo (Dummy drug) when used along with the standard therapy in patients with chronic heart failure in reducing incidence of worsening of this condition |
|
Scientific Title of Study
|
Study to Evaluate the Effect of Dapagliflozin on the Incidence of Worsening Heart Failure or Cardiovascular Death in Patients with Chronic Heart Failure with Reduced Ejection Fraction |
| Trial Acronym |
|
|
Secondary IDs if Any
|
| Secondary ID |
Identifier |
| Protocol No: D1699C00001 Version 1, Dated 26 OCT 2016 |
Protocol Number |
|
|
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
|
| Name |
Dr V K Chopra |
| Designation |
Director Heart Failure Program |
| Affiliation |
Medanta-The Medicity |
| Address |
Sector-38,
Gurgaon, Harayana
Gurgaon
HARYANA
122001
India |
| Phone |
091-9560398900 |
| Fax |
091-1244834111 |
| Email |
chopravk@gmail.com |
|
Details of Contact Person
Scientific Query
|
| Name |
Mr Tapankumar M Shah |
| Designation |
Country Head - Site Management and Monitoring – India |
| Affiliation |
AstraZeneca Pharma India Limited |
| Address |
Block N1, 12th Floor,
Manyata Embassy Business Park, Rachenahalli,
Outer Ring Road
Bangalore
KARNATAKA
560045
India |
| Phone |
91-9535104975 |
| Fax |
91-8067748857 |
| Email |
tapankumar.shah@astrazeneca.com |
|
Details of Contact Person
Public Query
|
| Name |
Mr Tapankumar M Shah |
| Designation |
Country Head - Site Management and Monitoring – India |
| Affiliation |
AstraZeneca Pharma India Limited |
| Address |
Block N1, 12th Floor,
Manyata Embassy Business Park, Rachenahalli,
Outer Ring Road
Bangalore
KARNATAKA
560045
India |
| Phone |
91-9535104975 |
| Fax |
91-8067748857 |
| Email |
tapankumar.shah@astrazeneca.com |
|
|
Source of Monetary or Material Support
|
| AstraZeneca AB (Study Sponsor company)
151 85 Sodertalje, Sweden
|
|
|
Primary Sponsor
|
| Name |
AstraZeneca AB |
| Address |
151 85 Södertälje, Sweden |
| Type of Sponsor |
Pharmaceutical industry-Global |
|
|
Details of Secondary Sponsor
|
|
|
Countries of Recruitment
|
Canada
Argentina
Brazil
Bulgaria
China
Czech Republic
Denmark
Germany
Hungary
India
Japan
Netherlands
Poland
Romania
Russian Federation
Slovakia
Sweden
Taiwan
United Kingdom
United States of America
Viet Nam |
Sites of Study
Modification(s)
|
| No of Sites = 18 |
| Name of Principal
Investigator |
Name of Site |
Site Address |
Phone/Fax/Email |
| Dr Manjinder Sandhu |
Artemis Hospital |
Sector-51, Gurgaon-122001, Haryana
Gurgaon
HARYANA |
91-818520234
91-1246767701
manjinder@artemishospitals.com |
| Dr Hemant Kokane |
B.J.G.M.C. & Sasoon General Hospital |
Department of Cardiology, Near Pune Railway Station,
Pune-411001, Maharastra
Pune
MAHARASHTRA |
91-20-26126010
91-20-26130991
hemantkokane@gmail.com |
| Dr Sunil Kumar Karna |
Bhanubhai and Madhunben Patel Cardiac Centre |
Shree Krishna Hospital, Gokal Nagar,
Karamsad-388325, Gujrat
Anand
GUJARAT |
91-2692-228671
91-2692-228493
sunilkk@charutarhealth.org |
| Dr Naik Ajay Madhukar |
Care Institute of Medical Sciences(CIMS) Hospital Private Limited |
Near. Shukan Mall, Off. Science City Road,
Sola Ahmedabad-380060, Gujrat
Ahmadabad
GUJARAT |
91-7930101166
91-7927712777
ajay.naik@cims.me |
| Dr Mahpaekar T Mashhadi |
DDMM Heart Institute |
Mission Road, Nadiad-387002,
Gujarat
Kheda
GUJARAT |
91-268-2555510
91-268-2557020
m.mashhadi@ddmmheart.org |
| Dr Bhupesh Shah |
Dr. Jivaraj Mehta Smarak Health Foundation |
Bakeri Medical Research Center,
Ratubhai Adani Arogyadham,
Dr. Jivaraj Mehta Marg,
Ahmedabad-38007
Ahmadabad
GUJARAT |
91-79-26639840
91-79-26601411
bhupeshshah.017@gmail.com |
| Dr Vimal Mehta |
G.B. Pant Hospital |
Room No-133, Academic Block, 1st Floor, Jawaharlal Nehru Marg, New Delhi- 110002
New Delhi
DELHI |
91-11-23212554
91-11-23212554
drvimalmehta@yahoo.co.in |
| Dr Santosh Kumar Sinha |
Ganesh Shankar Vidyarthi Memorial Medical College |
Kanpur – 208002
Uttar Pradesh
Kanpur Nagar
UTTAR PRADESH |
91-9670220088
91-11-23236604
fionasan@rediffmail.com |
| Dr Varun Bhargava |
Ganga Care Hospital |
3, Farmland,
Panchsheel Square, Wardha Road,
Nagpur-440012, Maharastra
Nagpur
MAHARASHTRA |
91-712-3982222
91-712-2420158
drvarun2007@rediffmail.com |
| Dr Mukund Anant Deshpande |
Govt. Medical College and Superspeciality Hospital |
Near Tukdoji Square, Hanuman Nagar,
Nagpur-440003
Nagpur
MAHARASHTRA |
91-712-2744671
91-712-2744489
drmukunddeshpande@gmail.com |
| Dr Dhurjati Prasad Sinha |
IPGME & R and SSKM Hospital |
Institute of Cardiovascular Sciences,
244, A J C Bose Road,
Kolkatta-700020
Kolkata
WEST BENGAL |
91-33-22230241
91-33-22230241
drdpsinha@gmail.com |
| Dr Milind Avdhoot Gadkari |
KEM Hospital Research Centre |
Department of Cardiology, 5th Floor,
Diamond Jubilee Building,
489 Rasta Peth,
Sardar Moodliar Road, Pune-411011
Pune
MAHARASHTRA |
91-20-66037522
91-20-66037522
gadkaris@gmail.com |
| Dr Kothiwale Veerappa Annasaheb |
KLEs Dr. Prabhakar Kore Hospital & MRC |
Belagavi-590010
Belgaum
KARNATAKA |
91-831-2473777
91-831-2470732
nov10kothiwale@yahoo.com |
| Dr Prashant Prabhakar Udgire |
Mahatma Gandhi Missions Medical College and Hospital |
Cardiology Department, N-6, Cidco-Aurangabad-431003
Aurangabad
MAHARASHTRA |
91-9503181111
prashant_udgire@rediffmail.com |
| Dr V K Chopra |
Medanta-The Medicity |
Sector-38,
Gurgaon, Harayana-122001
Gurgaon
HARYANA |
091-9560398900
091-1244834111
chopravk@gmail.com |
| Dr Rahul Sawant |
Noble Hospital Pvt. Ltd |
Department of Cardiology,
153, Magarpatta City Road Hadapsar,
Pune-411013, Maharastra
Pune
MAHARASHTRA |
91-20-66285000
91-20-66285199
drrahulsawant@hotmail.com |
| Dr Yogeshkumar A Kothari |
Rajarajeshwari Medical College and Hospital |
202, Kambipura, Mysore Road,
Bangalore-560074
Bangalore
KARNATAKA |
091-990197374
080-28437878
dryogeshkothari@gmail.com |
| Dr Jaideep Channayil Menon |
Sree Narayana Institute of Medical Sciences |
Department of Cardiology, Chalakka,
N. Kuthiyathodu, P.O. Ernakulam-683594
Ernakulam
KERALA |
91-484-2573023
91-484-2573060
drjaideepcmenon@gmail.com |
|
Details of Ethics Committee
Modification(s)
|
| No of Ethics Committees= 18 |
| Name of Committee |
Approval Status |
| Artemis Health Sciences Institutional Ethics Committee |
Approved |
| Care Hospital, Nagpur, Ethics Committee |
Approved |
| Ethics Committee MGM Medical College |
Approved |
| Ethics Committee of Care Institute of Medical Science |
Approved |
| Ethics Committee, G.S.V.M Medical College |
Approved |
| Ethics Committee, KLE University |
Approved |
| Ethics Committee, Shree Narayana Institute of Medical Sciences |
Approved |
| Gujrat Methodist Church Cardiothoracic & Vascular Research Society Institutional Ethics Committee |
Approved |
| Institutional Ethics Committee of BJ Govt. Medical College and Sassoon Government Hospital |
Approved |
| Institutional Ethics Committee, Dept. of Pharmacology, Govt. Medical College, Nagpur |
Approved |
| Institutional Ethics Committee, H M Patel Centre for Medical Care & Education |
Approved |
| Institutional Ethics Committee, Maulana Azad Medical College and Associated Hospitals |
Approved |
| Institutional Ethics Committee, Noble Hospital Pvt. Ltd. |
Approved |
| IPGME&R Research Oversight Committee |
Approved |
| KEM Hospital Research Centre, Ethics Committee |
Approved |
| Medanta Institutional Ethics Committee |
Approved |
| Rajarajeshwari Medical College and Hospital, Institutional Ethics Committee |
Approved |
| The JMSHF and BMRC Institutional Ethics Committee, |
Approved |
|
|
Regulatory Clearance Status from DCGI
|
|
Health Condition / Problems Studied
Modification(s)
|
| Health Type |
Condition |
| Patients |
Men and women ≥18 years of age with an established diagnosis of HFrEF for ≥ 2 months and at a high risk of CV death or HF events, (1) ICD-10 Condition: I258||Other forms of chronic ischemic heart disease, |
|
Intervention / Comparator Agent
Modification(s)
|
| Type |
Name |
Details |
| Intervention |
Dapagliflozin |
Dapagliflozin/Placebo Frequency: Once in a day Route of administration: Oral Total duration of therapy: 24 months |
| Comparator Agent |
Placebo |
Matching placebo for Dapagliflozin |
|
|
Inclusion Criteria
|
| Age From |
18.00 Year(s) |
| Age To |
99.00 Year(s) |
| Gender |
Both |
| Details |
1. Provision of signed informed consent prior to any study specific procedures
2. Male or female, aged ≥18 years at the time of consent
3. Established documented diagnosis of symptomatic HFrEF (NYHA functional class II-IV), which has been present for at least 2 months and is optimally treated with pharmacological and/or device therapy, as indicated
4. LVEF≤40% (echocardiogram, radionuclide ventriculogram, contrast angiography or cardiac MRI) within the last 12 months prior to enrolment (Visit 1)
5. NT-proBNP >600 pg/ml (or if hospitalized for heart failure within the previous 12 months, NT-proBNP ≥400 pg/ml) at enrolment (visit 1) |
|
| ExclusionCriteria |
| Details |
1. Receiving therapy with an SGLT2 inhibitor within 8 weeks prior to enrolment or previous intolerance of an SGLT2 inhibitor
2. Type 1 diabetes mellitus (T1D)
3. Symptomatic hypotension or systolic BP <95 mmHg on 2 consecutive measurements
4. Current acute decompensated HF or hospitalization due to decompensated HF <4 weeks prior to enrolment
5. MI, unstable angina, stroke or transient ischemic attack (TIA) within 12 weeks prior to enrolment
6. Coronary revascularization (percutaneous coronary intervention [PCI] or coronary artery bypass grafting [CABG]) or valvular repair/replacement within 12 weeks prior to enrolment or planned to undergo any of these operations after randomization
7. Implantation of a cardiac CRT within 12 weeks prior to enrolment or intent to implant a CRT device
8. Women of child-bearing potential (ie, those who are not chemically or surgically sterilised or who are not post-menopausal) who are not willing to use a medically accepted method of contraception that is considered reliable in the judgment of the investigator OR women who have a positive pregnancy test at enrolment or randomization OR women who are breast-feeding
|
|
|
Method of Generating Random Sequence
|
Stratified block randomization |
|
Method of Concealment
|
Centralized |
|
Blinding/Masking
|
Double Blind Double Dummy |
|
Primary Outcome
|
| Outcome |
TimePoints |
| To determine, as a superiority assessment, whether treatment with dapagliflozin 10 mg, when added to standard of care, will reduce the incidence of the composite endpoint of CV death or hospitalization for heart failure or equivalent HF event (hereafter referred to as Heart Failure Event) |
Time to the first occurrence of any of the components of this composite:
1. CV death
2. Hospitalisation for heart failure
3. An urgent heart failure visit
|
|
|
Secondary Outcome
|
| Outcome |
TimePoints |
| To compare the effect of dapagliflozin versus placebo on CV death or hospitalization for HF |
Time to the first occurrence of any of the components of this composite:
1. CV death
2. Hospitalization for HF |
| To compare the effect of dapagliflozin versus placebo on total number of recurrent HF hospitalizations and CV death. |
Total number of recurrent HF hospitalizations and CV death. |
To compare the effect of treatment with dapagliflozin versus placebo on the KCCQ
clinical summary score for HF symptoms and physical limitations. |
Change from baseline measured at 8 months in the overall summary score of the KCCQ, a specific HF patient reported outcome questionnaire. |
To determine if dapagliflozin compared with
placebo reduces the incidence of a worsening
renal function composite outcome |
Time to the first occurrence of any of the components of this composite:
1. ≥50% sustained decline in eGFR
2. Reaching End Stage Renal Disease
- Sustained eGFR less than 15 ml/min/1.73m2 or
- Chronic dialysis treatment or
- Receiving a renal transplant
3. Renal death |
|
|
Target Sample Size
|
Total Sample Size="7000"
Sample Size from India="700"
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)
|
14/08/2017 |
| Date of Study Completion (India) |
Applicable only for Completed/Terminated trials |
| Date of First Enrollment (Global) |
08/02/2017 |
| Date of Study Completion (Global) |
Applicable only for Completed/Terminated trials |
|
Estimated Duration of Trial
|
Years="4"
Months="0"
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
|
None yet |
|
Individual Participant Data (IPD) Sharing Statement
|
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
|
Brief Summary
Modification(s)
|
This is an international, multicentre, event-driven, randomized, double-blind, parallel group, placebo-controlled study to investigate whether dapagliflozin versus placebo, given once daily, compared with placebo, reduces the incidence of the composite endpoint of CV death or HF event (hospitalization for HF or equivalent event (i.e. an urgent HF visit)) when added to background standard of care treatment. The primary outcome will be Time to the first occurrence of any of the components of CV death, Hospitalisation for heart failure, An urgent heart failure visit. The study will be conducted in about 30 centres in India and globally around 20-25 countries. The sample size from India could be around 700 patients and 7000 patients from rest of the world. The duration of the study will be around 4 years. |