| CTRI Number |
CTRI/2017/08/009535 [Registered on: 29/08/2017] Trial Registered Prospectively |
| Last Modified On: |
27/04/2020 |
| 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 kidney disease in reducing incidence of worsening of this condition. |
|
Scientific Title of Study
|
A Study to Evaluate the Effect of Dapagliflozin on Renal Outcomes and Cardiovascular Mortality in Patients with Chronic Kidney Disease |
| Trial Acronym |
|
Secondary IDs if Any
Modification(s)
|
| Secondary ID |
Identifier |
| D169AC00001, Version 2.0 dated 26 Sep 2017 |
Protocol Number |
|
|
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
|
| Name |
Dr Dinesh Khullar |
| Designation |
Chairman and HOD |
| Affiliation |
Max Super Speciality Hospital |
| Address |
Dept. of Nephrology and Kidney Transplant
Max Super Speciality Hospital,
2 Press Enclave Road,
Saket, New Delhi-110017
New Delhi
DELHI
110017
India |
| Phone |
91-11-26515050 |
| Fax |
91-11-26510050 |
| Email |
drdineshkhullar@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
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 Sodertalje, Sweden |
| Type of Sponsor |
Pharmaceutical industry-Global |
|
|
Details of Secondary Sponsor
|
|
|
Countries of Recruitment
|
Argentina
Brazil
Canada
China
Denmark
Germany
Hungary
India
Mexico
Peru
Philippines
Poland
Republic of Korea
Romania
Russian Federation
Spain
Sweden
Ukraine
United Kingdom
United States of America
Viet Nam |
Sites of Study
Modification(s)
|
| No of Sites = 20 |
| Name of Principal
Investigator |
Name of Site |
Site Address |
Phone/Fax/Email |
| Dr Deepak Dewan |
Ajanta Hospital and IVF Centre |
765, ABC Complex, Kanpur Road, Alambagh,
Lucknow 226005, Uttar Pradesh
Lucknow
UTTAR PRADESH |
91-522-4101017
91-522-4101017
drdeepakdewan@rediffmail.com |
| Dr Arthur Joseph Asirvatham |
Arthur Asirvatham Hospital |
42-A Kuruvikkaran Salai, Anna Bus stand
Madurai-20
Madurai
TAMIL NADU |
91-452535266
91-4522531977
drarthurasirvatham@gmail.com |
| Dr Kamal Goplani |
B. J. Medical College & Civil Hospital |
Asarwa, Ahmedabad- 380016,
Gujrat
Ahmadabad
GUJARAT |
91-9909975020
kamalgoplani@gmail.com |
| Dr Yogesh Kadam |
CIMETS Inamdar Multispeciality Hospital |
Hospital Building S. No. 15, Fatima Nagar, Pune 411040,
Maharashtra
Pune
MAHARASHTRA |
91-20-66812499
dryogeshkadam@gmail.com |
| Dr Milind S Vyawahare |
Government Medical College and Hospital |
Near Hanuman Nagar, Medical Square,
Nagpur-440009
Nagpur
MAHARASHTRA |
91-712-2728621
drmilindvyawahare@yahoo.com |
| Dr Sreelatha Melemadathil |
Government Medical College, Kozhikode |
Department of Nephrology,
Government Medical College, Kozhikode,
Kerala- 673008
Kozhikode
KERALA |
91-4952350350
drsreelathacmc@gmail.com |
| Dr Edwin Fernando Mervin |
Govt. Stanley Medical College & Hospital |
Department of Nephrology,
Govt. Stanley Medical College & Hospital,
Old Jail Road, Chennai-600001, Tamilnadu
Chennai
TAMIL NADU |
91-44-2580910
91-44-2580910
dredwinresearch@gmail.com |
| Dr Vishal Kumar Gupta |
GSVM Medical College |
Post Graduate Department of Medicine,
GSVM Medical College, Swaroop Nagar,
Kanpur-208002, Uttar Pradesh
Kanpur Nagar
UTTAR PRADESH |
91-8765172558
drvkguptagsvm@gmail.com |
| Dr Rajendra Pandey |
Institute of Post Graduate Medical Education & Research |
Department of Nephrology
244AJC Bose Road, Kolkata-700020,
West Bengal
Kolkata
WEST BENGAL |
91-9433033163
rajensankrityan@gmail.com |
| Dr Girithara Gopalkrishnan |
KG Hospital and Post Graduate Medical Institute |
Department Of Diabetology,
No.5 Arts College Road,
Coimbatore- 641018
Coimbatore
TAMIL NADU |
91-4222212121
91-4222218721
drgirimd@yahoo.com |
| Dr Satyendra Sonkar |
King George’s Medical University, UP |
Assistant Professor
Department of Nephrology,
Lucknow - 226003
Uttar Pradesh
Lucknow
UTTAR PRADESH |
9307288648
satyendra.sonkar@gmail.com |
| Dr Dinesh Khullar |
Max Super Speciality Hospital |
2 Press Enclave Road,
Saket,
New Delhi-110017
New Delhi
DELHI |
91-11-26515050
91-11-26510050
drdineshkhullar@gmail.com |
| Dr Sameer Chaubey |
Meditrina Institute of Medical Sciences |
Central Bazar Road, Ramdaspeth, Nagpur-10,
Maharashtra
Nagpur
MAHARASHTRA |
91-9890944860
sameer144@gmail.com |
| Dr Avinash Ignatius |
Noble Hospital Pvt. Ltd |
Department of Nephrology,
153, Magarpatta City Road
Hadapsar,
Pune-411013
Pune
MAHARASHTRA |
91-20-66285000
dr_ignatius@yahoo.co.in |
| Dr Sanjay Chunilal Agarwal |
Ruby Hall Clinic |
Grant Medical Foundation, Ruby Hall Clinic, 40 Sassoon Road, Pune-411001
Pune
MAHARASHTRA |
91-9822091220
agarwalclinic@gmail.com |
| Dr Pulichikkat Kesavan Rakesh |
Sree Narayana Institute of Medical Sciences |
Chalakka, N. Kuthiyathodu P.O.
Ernakulam, Pin-683594, Kerala
Ernakulam
KERALA |
91-484-2573023
drrakeshpulichikkat@gmail.com |
| Dr A Venkateshwar Rao |
St. Theresa’s Hospital |
Sanathnagar, Hydrabad-500018, Telangana State
Hyderabad
ANDHRA PRADESH |
91-40-23701013
91-40-23814556
venki_gmc@yahoo.co.in |
| Dr Krishna MVS |
Sunrise Hospitals |
Opp. Corporation bank,
Bellapu Sobhanadri Road,
Near Pushpa hotel Center, Vijaywada-522002,
Andhra Pradesh
Visakhapatnam
ANDHRA PRADESH |
91-866-2434646
krishnamvs@yahoo.com |
| Dr KG Prakash |
Victoria Hospital |
#63/A, Ground floor, New C Block, Dept. of Medicine,
Victoria Hospital, BMCRI, K.R. Road, Fort,
Bangalore - 560002
Bangalore
KARNATAKA |
91-80-26706067
91-80-26706067
kikkeri47@yahoo.com |
| Dr Hansraj Alva |
Vinaya Hospital and Research Center |
P O Box 717, Karangalpady, Mangalore-575003,
Karnataka
Dakshina Kannada
KARNATAKA |
91-9343562622
hansrajalva@gmail.com |
|
Details of Ethics Committee
Modification(s)
|
| No of Ethics Committees= 20 |
| Name of Committee |
Approval Status |
| BJ Medical College and Civil Hospital |
Approved |
| Ethics Committee Inamdar Multispeciality Hospital |
Approved |
| Ethics Committee of Bangalore Medical College and Research Institute |
Approved |
| Ethics Committee, G.S.V.M Medical College |
Approved |
| Ethics Committee, Govt. Medical College, Kozhikode |
Approved |
| Ethics Committee, Sree Narayana Institute of Medical Sciences |
Approved |
| Ethics Committee, St. Theresa Hospital |
Approved |
| Ethics Committee, Vinaya Hospital |
Approved |
| Govt. Stanley Medical College |
Approved |
| Institutional EC, Max Healthcare at Max Super Specialty Hospital |
Approved |
| Institutional Ethics Committee for Ajanta Hospital and IVF Centre |
Approved |
| Institutional Ethics Committee King Georges Medical University, UP |
Approved |
| Institutional Ethics Committee, Arthur Asirvatham Hospital |
Approved |
| Institutional Ethics Committee, Govt. Medical College, Nagpur |
Approved |
| Institutional Ethics Committee, Sunrise Hospital |
Approved |
| IPGME&R Research Oversight Committee |
Approved |
| Meditrina Institute Ethics Committee |
Approved |
| Noble Hospital Institutional Ethics Committe |
Approved |
| Poona Medical Research Foundation |
Approved |
| Regional Ethics Committee, KG Hospital |
Approved |
|
|
Regulatory Clearance Status from DCGI
|
|
Health Condition / Problems Studied
Modification(s)
|
| Health Type |
Condition |
| Patients |
(1) ICD-10 Condition: N182||Chronic kidney disease, stage 2 (mild), Men and women ≥18 years of age with Chronic Kidney Disease., |
|
Intervention / Comparator Agent
Modification(s)
|
| Type |
Name |
Details |
| Intervention |
Dapagliflozin |
Dapagliflozin Tablets |
| 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. Female or male aged ≥18 years at the time of consent
3. eGFR ≥25 and ≤75 mL/min/1.73m2 (CKD-EPI Formula) at visit 1
4. UACR ≥200 and ≤5000 mg/g at visit 1
5. Stable, and for the patient maximum tolerated labelled daily dose, treatment with ACE-I or ARB for at least 4 weeks before visit 1, if not medically contraindicated
|
|
| ExclusionCriteria |
| Details |
1. Autosomal dominant or autosomal recessive polycystic kidney disease, lupus nephritis or ANCA-associated vasculitis
2. Receiving cytotoxic therapy, immunosuppressive therapy or other immunotherapy for primary or secondary renal disease within 6 months prior to enrolment
3. History of organ transplantation
4. Receiving therapy with an SGLT2 inhibitor within 8 weeks prior to enrolment or previous intolerance of an SGLT2 inhibitor
5. Type 1 diabetes mellitus (T1D)
6. New York Heart Association (NYHA) class IV Congestive Heart Failure at the time of enrolment (see Appendix C)
7. MI, unstable angina, stroke or transient ischemic attack (TIA) within 12 weeks prior to enrolment
8. Coronary revascularization (percutaneous coronary intervention [PCI] or coronary artery bypass grafting [CABG]) or valvular repair/replacement within 12 weeks prior to enrolment or is planned to undergo any of these procedures after randomization
9. Any condition outside the renal and CV disease area, such as but not limited to malignancy, with a life expectancy of less than 2 years based on investigator´s clinical judgement
10. Active malignancy requiring treatment at the time of visit 1 (with the exception of successfully treated basal cell or treated squamous cell carcinoma).
11. Hepatic impairment (aspartate transaminase [AST] or alanine transaminase [ALT] >3x the upper limit of normal [ULN]; or total bilirubin >2x ULN at time of enrolment)
12. Known blood borne diseases such as specified in Appendix B (category A and B)
13. 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 if dapagliflozin is superior to placebo in reducing the incidence of the primary composite endpoint of more than 50% sustained decline in estimated glomerular filtration rate (eGFR), reaching end stage renal disease (ESRD), CV or renal death when added to current background therapy in patients with eGFR less than 25 and less than 75 ml/min/1.73m2 and albuminuria (urine albumin creatinine ratio [UACR] more than 200 and less than 5000 mg/g). |
1. 50% sustained decline in eGFR
2. Reaching ESRD
a. Sustained eGFR less than15 mL/min/1.73m2 or,
b. Chronic dialysis treatment or,
c. Receiving a renal transplant
3. CV death
4. Renal death
|
|
|
Secondary Outcome
|
| Outcome |
TimePoints |
| To determine whether dapagliflozin compared with placebo will result in a reduction of the incidence of the composite endpoints of worsening of renal function. |
1. more than 50% sustained decline in eGFR
2. Reaching ESRD
3. Renal death
4. CV death
5. Hospitalization for heart failure
|
|
|
Target Sample Size
|
Total Sample Size="4000"
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)
|
11/09/2017 |
| Date of Study Completion (India) |
Applicable only for Completed/Terminated trials |
| Date of First Enrollment (Global) |
02/02/2017 |
| 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
|
This is an international, multicentre, event-driven, randomized, double-blind, parallel group, placebo-controlled study to investigate whether dapagliflozin 10 mg versus placebo, given once daily, compared with placebo, reduces the incidence of the primary composite endpoint of ≥50% sustained decline in estimated glomerular filtration rate (eGFR), reaching end stage renal disease (ESRD), CV or renal deathwhen added to background standard of care treatment. The primary outcome will be 50% sustained* decline in eGFR, reaching ESR, sustained eGFR <15 mL/min/1.73m2 or, chronic dialysis treatment or receiving a renal transplant, CV death and renal death. 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 600 patients and 4000 patients from rest of the world. The duration of the study will be around 4 years. |