Aliskiren Trial in Type 2 Diabetes Using Cardiovascular and Renal Disease Endpoints Including 12 Month Safety Follow-up Off-treatment - Full Text View

Purpose

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.

Condition	Intervention	Phase
Type 2 Diabetes Mellitus Cardiovascular Disease	Drug: Aliskiren Drug: Placebo	Phase 3

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Investigator) Primary Purpose: Treatment
Official Title:	A Randomized, Double-blind, Placebo-controlled, Parallel Group 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

Resource links provided by NLM:

MedlinePlus related topics: Diabetes Diabetes Type 2 Heart Attack

Drug Information available for: Aliskiren

U.S. FDA Resources

Further study details as provided by Novartis:

Primary Outcome Measures:

Cardiovascular (CV) death [ Time Frame: Time from randomization to the first event ] [ Designated as safety issue: No ]
Resuscitated sudden death [ Time Frame: Time from randomization to the first event ] [ Designated as safety issue: No ]
Non-fatal myocardial infarction (MI) [ Time Frame: Time from randomization to the first event ] [ Designated as safety issue: No ]
Non-fatal stroke [ Time Frame: Time from randomization to the first event ] [ Designated as safety issue: No ]
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 [ Time Frame: Time from randomization to the first event ] [ Designated as safety issue: No ]
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 Measures:

Time from randomization to the first event of the following composite CV endpoint: • Cardiovascular (CV) death • Resuscitated sudden death • Non-fatal myocardial infarction (MI) [ Time Frame: time of first event ] [ Designated as safety issue: No ]
Time from randomization to the first event of the following composite CV endpoint: • Non-fatal stroke • Unplanned hospitalization for heart failure (HF) [ Time Frame: time of first event ] [ Designated as safety issue: No ]
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 [ Time Frame: time from randomization to the first event ] [ Designated as safety issue: No ]
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 ]

Enrollment:	8606
Study Start Date:	October 2007
Estimated Study Completion Date:	February 2013
Estimated Primary Completion Date:	February 2013 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Aliskiren Double-blind aliskiren 150 mg o.d.	Drug: Aliskiren Aliskiren 300 mg OD
Placebo Comparator: Placebo Double-blind placebo to match aliskiren 150 mg o.d	Drug: Placebo Placebo

Eligibility

Ages Eligible for Study:	35 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

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.

Exclusion Criteria:

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.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00549757

Show 778 Study Locations

Sponsors and Collaborators

Novartis Pharmaceuticals

Investigators

Study Director:	Novartis Pharmaceuticals	Novartis Pharmaceuticals
Study Chair:	Novartis	Novartis

More Information

No publications provided by Novartis

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

Responsible Party:	Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:	NCT00549757 History of Changes
Other Study ID Numbers:	CSPP100E2337, 2007-000860-25
Study First Received:	October 24, 2007
Last Updated:	February 4, 2013
Health Authority:	United States: Food and Drug Administration Argentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia Medica Austria: Federal Office for Safety in Health Care Belgium: Federal Agency for Medicinal Products and Health Products Brazil: Ministry of Health Canada: Health Canada China: Food and Drug Administration Colombia: INVIMA Instituto Nacional de Vigilancia de Medicamentos y Alimentos Czech Republic: State Institute for Drug Control Denmark: Danish Medicines Agency Finland: Finnish Medicines Agency France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis) Germany: Federal Institute for Drugs and Medical Devices Greece: National Organization of Medicines Guatemala: Ministry of Public Health and Social Assistance Hungary: National Institute of Pharmacy India: Central Drugs Standard Control Organization Italy: National Institute of Health Japan: Pharmaceuticals and Medical Devices Agency Korea: Food and Drug Administration Lithuania: State Medicine Control Agency - Ministry of Health Netherlands: Medicines Evaluation Board (MEB) Norway: Norwegian Medicines Agency Peru: General Directorate of Pharmaceuticals, Devices, and Drugs Portugal: National Pharmacy and Medicines Institute Singapore: Center for Drug Administration Slovakia: State Institute for Drug Control South Africa: Medicines Control Council Spain: Spanish Agency of Medicines Sweden: Medical Products Agency Switzerland: Swissmedic Taiwan: Department of Health Thailand: Ministry of Public Health Turkey: General Directorate of Pharmaceuticals and Pharmacy United Kingdom: Medicines and Healthcare Products Regulatory Agency Venezuela: Ministry of Health and Social Development

Keywords provided by Novartis:

Type 2 diabetes mellitus
renal morbidity and mortality
cardiovascular disease
micro-albuminuria

macro-albuminuria
RAAS
renin inhibitor
Reduced estimated glomerular filtration rate

Additional relevant MeSH terms:

Cardiovascular Diseases
Diabetes Mellitus
Diabetes Mellitus, Type 2

Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases

ClinicalTrials.gov processed this record on May 23, 2013

Aliskiren Trial in Type 2 Diabetes Using Cardiovascular and Renal Disease Endpoints Including 12 Month Safety Follow-up Off-treatment (ALTITUDE)