Aliskiren Trial in Type 2 Diabetes Using Cardiovascular and Renal Disease Endpoints (Core and Extension Phases)
Condition: Type 2 Diabetes Mellitus; Cardiovascular Disease
MeSH terms: Cardiovascular Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2
Intervention: Aliskiren; Placebo
Intervention description: Aliskiren 150 mg film-coated tablets; Placebo to match aliskiren 150 mg film-coated tablets
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 8606.0
Sex: All
Minimum age: 35 Years
Healthy volunteers: No
Keywords: Type 2 diabetes mellitus; renal morbidity and mortality; cardiovascular disease; micro-albuminuria; macro-albuminuria; RAAS; renin inhibitor; Reduced estimated glomerular filtration rate

Summary:

      The purpose of this study was 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 served to address the data monitoring committee recommendation dated 14
      Dec 2011 to discontinue study treatment in all participating patients. It also addressed the
      subsequent Health Authorities request to implement a 12 month safety follow-up period (actual
      duration was 9 months in average) post study drug discontinuation.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Type 2 diabetes and at least one of the following:

               -  Macroalbuminuria and an eGFR ≥30 mL/min/1.73 m2

               -  Microalbuminuria and a reduced kidney function (eGFR eGFR ≥30 and <60 mL/min/1.73
                  m2)

               -  A history of CV disease (previous MI, previous stroke, heart failure, coronary
                  artery disease, history of percutaneous coronary intervention, angiography proven
                  stenosis ≥50% in at least one coronary artery and a reduced kidney function (eGFR
                  ≥30 and <60 mL/min/1.73 m2)

          -  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 applied