| CTRI Number |
CTRI/2008/091/000001 [Registered on: 22/08/2008] |
| Last Modified On: |
13/04/2013 |
| Post Graduate Thesis |
No |
| Type of Trial |
Interventional |
Type of Study
Modification(s)
|
Drug |
| Study Design |
Randomized, Parallel Group, Placebo Controlled Trial |
Public Title of Study
Modification(s)
|
ALiskiren Trial In Type 2 diabetes Using cardiorenal
Disease Endpoints |
Scientific Title of Study
Modification(s)
|
A randomized, double-blind, placebo-controlled, parallelgroup study to determine whether, in patients with type 2 diabetes at high risk for cardiovascular and renal events, aliskiren, on top of conventional treatment, reduces cardiovascular and renal morbidity and mortality |
| Trial Acronym |
ALTITIUDE |
Secondary IDs if Any
Modification(s)
|
| Secondary ID |
Identifier |
| NCT00549757 |
ClinicalTrials.gov |
|
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
Modification(s)
|
| Name |
Bipin Kumar Sethi |
| Designation |
National Coordinator |
| Affiliation |
Consultant Endocrinologist |
| Address |
Care Hospital, 8-2- 620/A-E, Road # 10 Banjara Hills, Hyderabad - 500 034.
Hyderabad
ANDHRA PRADESH
500 034.
India |
| Phone |
919848021482 |
| Fax |
914039310772 |
| Email |
bipinkumarsethi@yahoo.co.uk |
|
Details of Contact Person
Scientific Query
Modification(s)
|
| Name |
Ilse Devrieze |
| Designation |
Global Trial Leader |
| Affiliation |
Global Trial Leader |
| Address |
Novartis Pharma AG, Postfach, CH-4002 Basel, SWITZERLAND
Basel CH-4002
Other |
| Phone |
0041613246136 |
| Fax |
0041613242889 |
| Email |
ilse.devrieze@novartis.com |
|
Details of Contact Person
Public Query
Modification(s)
|
| Name |
Akshatha Shetty |
| Designation |
Clinical Study Manager |
| Affiliation |
Clinical Study Manager |
| Address |
Novartis Healthcare Private Limited
Sandoz House, 5th floor, Shivsagar Estate
Dr. Annie Besant Road, Worli, Mumbai 400 018
INDIA
Mumbai
MAHARASHTRA
Mumbai 400 018
India |
| Phone |
00912224958585 |
| Fax |
009122494112 |
| Email |
akshatha.shetty@novartis.com |
|
Source of Monetary or Material Support
Modification(s)
|
| Novartis Pharma AG, Postfach, CH-4002 Basel, SWITZERLAND |
|
Primary Sponsor
Modification(s)
|
| Name |
Novartis Pharma |
| Address |
Novartis Pharma AG, Postfach, CH-4002 Basel, SWITZERLAND |
| Type of Sponsor |
Pharmaceutical industry-Global |
|
Details of Secondary Sponsor
Modification(s)
|
| Name |
Address |
| Novartis Healthcare Private Limited |
Sandoz House, 5th floor, Shivsagar Estate
Dr. Annie Besant Road, Worli, Mumbai 400 018, INDIA |
|
Countries of Recruitment
Modification(s)
|
Argentina
Austria
Belgium
Brazil
Canada
China
Colombia
Czech Republic
Denmark
Finland
France
Germany
Greece
Guatemala
Hungary
India
Italy
Japan
Lithuania
Netherlands
Peru
Portugal
Singapore
Slovakia
South Africa
Spain
Switzerland
Taiwan
Thailand
Turkey
United Kingdom
United States of America
Venezuela (Bolivarian Republic of) |
Sites of Study
Modification(s)
|
| No of Sites = 20 |
| Name of Principal
Investigator |
Name of Site |
Site Address |
Phone/Fax/Email |
| Dr Nikhil Tandon |
All India Institute of Medical Sciences |
All India Institute of Medical Sciences,Department of Endocrinology and Metabolism, Room # 311/ Biotechnology,Ansari Nagar, New Delhi - 110 029
New Delhi
DELHI |
09818211663
911126588663
nikhil_tandon@hotmail.com |
| Dr Harish Kumar |
Amrita Institute of Medical Sciences and Research Centre |
Amrita Lane,Elamakkara Post, Kochi,Kerala - 682 026, Kochi
Thiruvananthapuram
KERALA |
919846005343
914842802131
harishkumar@aims.amrita.edu |
| Dr Bipin Kumar Sethi |
Care Hospital |
Care outpatient centre, 8-2-620/A-E, Road # 10, Banjara Hills, Hyderabad - 500 034.
Hyderabad
ANDHRA PRADESH |
919848021482
914066258792
bipinkumarsethi@yahoo.co.uk |
| Dr Nihal Thomas |
Christian Medical College |
Chapel Building, 2nd Floor, Room no. 801, Dept of Endocrinology, Vellore - 632 004 Tamil Nadu.
Vellore
TAMIL NADU |
919843111996
914164200854
nihal_thomas@yahoo.com |
| Dr VSeshaih |
Dr V Seshiah Diabetes Care and Research Institute, |
Dr. V. Seshiah Research Institute and Dr. Balaji Diabetes Care Centre. # 729, P.H. Road, Aminjikarai, Chennai - 600 029
Chennai
TAMIL NADU |
919382783760
914426640660
vseshiah@gmail.com |
| Prof Subhankar Chowdhury |
Institute of Post Graduate Medical Education & Research and SSKM Hospital |
Institute of Post Graduate Medical Education & Research and SSKM Hospital,244 AHC Bose Road,Kolkata 700 019.
Kolkata
WEST BENGAL |
919831076501
913322235076
subhankar.chowdhury@gmail.com |
| Dr Prabha Adhikari |
Kasturba Medical College |
MCCR, 7th floor,
KMC Hospital,
Attavar, Mangalore
575001
Bangalore
KARNATAKA |
919880991290
918242425092
adhikari_pmr@yahoo.com |
| Dr C S Yajnik |
KEM Hospital |
Coyaji Building, 6th Floor Rasta Peth, PUNE 411 011
Pune
MAHARASHTRA |
0919822847481
0912026111958
csyajnik@hotmail.com |
| Dr Sameer Dani |
Life care Institue of Medical Sciences & Research |
Life Care Emergency Centre,
Life care Institue of Medical Sciences & Research, 3rd Floor, Room # 315,
Sardar Patel Statue Corner stadium road
Ahmedabad - 380 014.
Ahmadabad
GUJARAT |
919825038855
917926405210
drsameerdani@yahoo.com |
| Dr Arpan Bhattacharyya |
Lotus Diagnostic Centre |
"493,CMH Road,
Indira Nagar,
Bangalore - 560038.
India
Bangalore
KARNATAKA |
919886051410
918025257500
arpan@diabetesendocrinology.in |
| Dr Mala Dharmalingam |
M.S.Ramaiah Memorial Hospital |
M.S.Ramaiah Clinical Research Centre
M.S.Ramaiah Medical College and Hospitals
1st floor, M.S.Ramaiah Advanced Learning Centre,
Gnanagangothri campus, Gate-4
New BEL Road, MSRIT Post
Bangalore-560054
Bangalore
KARNATAKA |
919845208163
918022183012
endocrinology23@rediffmail.com |
| Dr Vijay Viswanathan |
M.V. Hospital for Diabetes and Diabetic Research Center |
# 5 West Mada Chruch Street,Royapuram-600013
Chennai
TAMIL NADU |
919840055535
914425983444
drvijay@mvdiabetes.com |
| Dr V Mohan |
Madras Diabetes Research Foundation |
# 4,Coran Smith Road,Gopalapuram Chennai-600 086
Chennai
TAMIL NADU |
919840134505
914428350935
drmohans@vsnl.net |
| Dr Rakesh Kumar Sahay |
Mediciti Hospitals |
5-9-22, Sarovar Complex, Secretariat Road, Hyderabad - 500063, A.P.
Hyderabad
ANDHRA PRADESH |
919849597507
914023299078
rakeshsahay@rediffmail.com |
| Dr KirtiKumar D Modi |
Medwin hospitals, |
Raghava Ratna Towers,Nampally-500002
Hyderabad
ANDHRA PRADESH |
919848115322
9104066623441
drkdmodi@yahoo.co.in |
| Dr P Vishnupriya Rao |
Nizams Institute of Medical Sciences |
Panjagutta
Hyderabad - 500 082
Hyderabad
ANDHRA PRADESH |
919885051110
914023320111
diabtrials@gmail.com |
| Dr Sampath Kumar |
Osmania General Hospital |
Dept. of Cardiology
Afzalgunj
Hyderabad
Hyderabad
ANDHRA PRADESH |
919848033468
914024736313
drsampath53@yahoo.com |
| Dr Hiremath Jagdish S |
Poona Hospital & Research Centre, |
27, Sadashivpet, Pune - 411 030.
Pune
MAHARASHTRA |
919822022441
912024336444
drjagdishhiremath@gmail.com |
| Dr Ganapathi B |
St.Johns Medical College |
St. Johns Medical College Hospital, Clinical Trials, Room # 7,Opp. to department of plastic surgery,Old O.P. Department
Koramangala ,Bangalore - 560 034
Bangalore
KARNATAKA |
919884067318
918025635313
mallyaganapathi@rediffmail.com |
| Dr P Varthakavi |
Topiwala National Medical College & BYL Nair Hospital |
Dr A.L.Nair Road, Mumbai Central Mumbai - 400 008.
Mumbai
MAHARASHTRA |
919224480560
912223080601
nairendo@gmail.com |
|
Details of Ethics Committee
Modification(s)
|
| No of Ethics Committees= 20 |
| Name of Committee |
Approval Status |
| Care Foundation Institutional Ethics Committee |
Approved |
| CLINICOM |
Approved |
| Ethical Review Board M S Ramaiah Medical College and Teaching Hospital |
Approved |
| Ethics Comittee Dr. V Seshiah Diabetes Care and Research Institute |
Approved |
| Ethics Committee All India Institute of Medical Sciences |
Approved |
| Ethics Committee B.Y.L.NAIR CH. Hospital and T.N.Medical College |
Approved |
| Ethics Committee Diabetes Research Center |
Approved |
| Ethics Committee Life Care Institute of Medical Sciences & Research |
Approved |
| Ethics Committee Osmania Medical College |
Approved |
| Ethics Committee Poona Hospital & Research Centre |
Approved |
| Institutional Ethical Review Board St. Johns Medical College & Hospital |
Approved |
| Institutional Ethics Committee Amrita Institute of Medical Sciences and Research Centre |
Approved |
| Institutional Ethics Committee Institute of Post Graduate Medical Education & Research |
Approved |
| Institutional Ethics Committee Kasturba Medical College |
Approved |
| Institutional Ethics Committee KEM hospital and Research Centre |
Approved |
| Institutional Ethics Committee Madras Diabetes Research Foundation |
Approved |
| Institutional Ethics Committee Medwin Hospitals |
Approved |
| Institutional Ethics Committee Nizams Institute of Medical Sciences |
Approved |
| Institutional Review Board Christian Medical College |
Approved |
| The Ethics Committee SHARE (Science Health Allied Research & Education) Organization |
Approved |
|
Regulatory Clearance Status from DCGI
Modification(s)
|
|
Health Condition / Problems Studied
Modification(s)
|
| Health Type |
Condition |
| Patients |
type 2 diabetes at high risk for cardiovascular and renal events, |
|
Intervention / Comparator Agent
Modification(s)
|
| Type |
Name |
Details |
| Intervention |
• Aliskiren 150 mg film-coated tablets
• Placebo to match aliskiren 150 mg film-coated tablets
• Aliskiren 300 mg film-coated tablets
• Placebo to match aliskiren 300 mg film-coated tablets
|
At randomization, patients who fulfill all eligibility criteria will be randomized to receive aliskiren 150 mg OD or placebo on top of their conventional treatment. 4 weeks after randomization, patients will be uptitrated to aliskiren target dose of 300 mg OD or placeboplacebo |
| Comparator Agent |
Placebo |
|
|
Inclusion Criteria
Modification(s)
|
| Age From |
35.00 Year(s) |
| Age To |
0.00 Year(s) |
| Gender |
Both |
| Details |
•Age greater than 35 years
•Type 2 diabetes and at least one of the following:
•Macroalbuminuria
•Microalbuminuria and a reduced kidney function
•Previous heart attack and a reduced kidney function
•Previous stroke and a reduced kidney function
•Heart Failure a reduced kidney function
•Coronary artery disease a reduced kidney function
•Concomitant treatment should follow national guidelines and must include either an Angiotensin-converting-enzyme-inhibitor (ACEi) or an Angiotensin-receptor-blocker (ARB) but not both. |
|
| ExclusionCriteria |
| Details |
• Type 1 diabetes mellitus
• Cardiovascular event or procedure ≤ 3 months prior to Visit 1
• Unstable serum creatinine
• Hypertension: Mean sitting systolic blood pressure (msSBP) ≥ 135 and 170 mmHg or Mean sitting diastolic blood pressure (msDBP) ≥ 85 and 110 mmHg unless treated with at least 3 anti-hypertensive medications
• Hypertension msSBP ≥ 170 or msDBP ≥ 110 mmHg
• Baseline Serum Potassium 5.0 mmol/L
• Patients who are treated with two renin-angiotensin-aldosterone-system-blockers
• Patients with NYHA class III or IV heart failure
• Known renal artery stenosis
• Previous randomization into the AVOID trial (CSPP100C2201)
EXCLUSION SPECIFIC TO THE SAFETY FOLLOW-UP PERIOD:
- Aliskiren or aliskiren containing fixed combination products must not be used
Other protocol-defined inclusion/exclusion criteria may apply. |
|
Method of Generating Random Sequence
Modification(s)
|
Computer generated randomization |
Method of Concealment
Modification(s)
|
Centralized |
Blinding/Masking
Modification(s)
|
Participant, Investigator, Outcome Assessor and Date-entry Operator Blinded |
Primary Outcome
Modification(s)
|
| Outcome |
TimePoints |
• Cardiovascular (CV) death
• Resuscitated sudden death
• Non-fatal myocardial infarction (MI)
• Non-fatal stroke
• Onset of end-stage renal disease (ESRD) defined as initiation of dialysis, renal transplantation, or a serum creatinine concentration above 6.0 mg/dL (530 µmol per liter) or renal death
• Doubling of baseline serum creatinine concentration to above the upper limit of normal according to the central laboratory, sustained for at least one month
|
Time Frame: Time from randomization to the first event, Designated as safety issue: No
|
|
Secondary Outcome
Modification(s)
|
| Outcome |
TimePoints |
•Time from randomization to the first event of the following composite CV endpoint: Cardiovascular (CV) death, Resuscitated sudden death, Non-fatal myocardial infarction (MI), Non-fatal stroke, Unplanned hospitalization for heart failure (HF)
•Onset of end-stage renal disease (ESRD) defined as initiation of dialysis, renal transplantation, or a serum creatinine concentration above 6.0 mg/dL (530 µmol per liter) or renal death
|
Doubling of baseline serum creatinine concentration to above the upper limit of normal according to the central laboratory, sustained for at least one month
For 1, 2 - Time Frame: time of first event, designated as safety issue: No
For 3, 4 - time from randomization to the first event, designated as safety issue: No |
|
Target Sample Size
Modification(s)
|
Total Sample Size="8606"
Sample Size from India="476"
Final Enrollment numbers achieved (Total)= ""
Final Enrollment numbers achieved (India)="" |
Phase of Trial
Modification(s)
|
Phase 3 |
Date of First Enrollment (India)
Modification(s)
|
01/05/2008 |
| Date of Study Completion (India) |
Date Missing |
| Date of First Enrollment (Global) |
10/10/2007 |
| Date of Study Completion (Global) |
Date Missing |
Estimated Duration of Trial
Modification(s)
|
Years="4"
Months="0"
Days="0" |
Recruitment Status of Trial (Global)
Modification(s)
|
Completed |
| Recruitment Status of Trial (India) |
Completed |
Publication Details
Modification(s)
|
•Parving HH, Brenner BM, McMurray JJ, de Zeeuw D, Haffner SM, Solomon SD, Chaturvedi N, Persson F, Desai AS, Nicolaides M, Richard A, Xiang Z, Brunel P, Pfeffer MA; ALTITUDE Investigators. Cardiorenal end points in a trial of aliskiren for type 2 diabetes. N Engl J Med. 2012 Dec 6;367(23):2204-13. doi: 10.1056/NEJMoa1208799. Epub 2012 Nov 3.
•Lambers Heerspink HJ, Perkovic V, de Zeeuw D. Renal and cardio-protective effects of direct renin inhibition: a systematic literature review. J Hypertens. 2009 Dec;27(12):2321-31. |
|
Individual Participant Data (IPD) Sharing Statement
|
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
|
Brief Summary
Modification(s)
|
The purpose of this study is to determine whether, in patients with type 2 diabetes and pre-existing disease of the heart and the circulatory system and/or the kidney, aliskiren at a target dose of 300 mg once daily (compared to placebo), on top of conventional treatment, reduces death and disease caused by the heart, the circulatory system and the kidney.
AMENDMENT 4 RATIONALE (MARCH 2012) :
Protocol amendment 4 serves to address the data monitoring committee recommendation dated 14 Dec 2011 to discontinue study treatment in all participating patients. It also addresses the subsequent Health Authorities request to implement a 12 month safety follow-up period post study drug discontinuation. |