Aliskiren Trial in Type 2 Diabetes Using Cardiovascular and Renal Disease Endpoints (Core and Extension Phases) (ALTITUDE)

Novartis

Status and phase: Terminated; Phase 3

Conditions: Type 2 Diabetes Mellitus; Cardiovascular Disease

Treatments: Drug: Aliskiren; Drug: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT00549757

CSPP100E2337

2007-000860-25 (EudraCT Number)

Details and patient eligibility

About

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.

Enrollment: 8,606 patients

Sex: All

Ages: 35+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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8,606 participants in 2 patient groups, including a placebo group

Aliskiren

Experimental group

Description:

In Core (Double Blind) phase, Aliskiren 150 mg once daily (o.d.) for 4 weeks; then patient was uptitrated to 300 mg o.d. at Visit 5/Week 4 (or 150 mg o.d. if patient could not tolerate target dose of study drug). Visits took place at 1, 4 , 5, 8 and 12 weeks after randomization (Visit 3/Week 0). Subsequent visits were planned every three months until end of core phase. With the recommendation of Data Monitoring Committee (DMC), after discontinuation of study drug, a follow up was added as Extension Phase (9 months in average) with no active treatment

Treatment:

Drug: Aliskiren

Placebo

Placebo Comparator group

Description:

In Core (Double Blind) phase, placebo to match aliskiren 150 mg once daily (o.d.) for 4 weeks; from Visit 5/Week 4 placebo to match aliskiren 300 mg o.d. (or placebo to match aliskiren 150 mg if patient could not tolerate target dose of study drug). Visits took place 1, 4 , 5, 8 and 12 weeks after randomization (Visit 3/Week 0). Subsequent visits were planned every three months until end of core phase. With the recommendation of Data Monitoring Committee (DMC), after discontinuation of study drug, a follow up was added as Extension Phase (9 months in average) with no active treatment.

Treatment:

Drug: Placebo