ALTITUDE: ALiskiren Trial in Type 2 diabetes Using cardio-renal Disease Endpoints (CSPP100E2337)
PI: Lois Katz, MD
ALTITUDE is a randomized, double-blind, placebo-controlled, parallel-group study to determine whether, in patients with type 2 diabetes at high risk for cardiovascular (CV) and renal events, aliskiren, on top of conventional treatment reduces cardiovascular and renal morbidity and mortality. Novartis is the study sponsor.
Objective: To determine whether aliskiren, when added to conventional treatment, compared to placebo, delays the occurrence of CV death, resuscitated sudden death, non-fatal MI, non-fatal stroke, unplanned hospitalization for CHF, onset of ESRD or renal, and doubling of baseline serum creatinine concentration, sustained for a least one month.
Methods: Multinational study. Plan is to randomize 8600 patients (4300 per arm). Our site will screen enough patients to randomize 20-30 patients. Eligible patients are men or women (aged 35 or older) with diabetes who may be treated with either oral anti-diabetes drugs or insulin. They must also have one of the following: persistent macroalbuminuria, persistent microalbuminuria, or history of CV disease and an eGFR > or = 30 and <60 mL/min/1.73m2. Patients must be treated with either an ACEI or ARB. Patients with serious other medical conditions, uncontrolled hypertension, drug or alcohol abuse within 12 months, a history of noncompliance with medications, or a life expectancy of <2 years will not be enrolled. All patients will sign written informed consent prior to enrollment in the screening period. The study has 2 phases:
Goal BP throughout the trial is 135/85 mmHg. During the study the patients will have first morning void urine samples for UACR and eGFR measurements once during screening and every 3 months for 1 year and then every 6 months. Ambulatory BP monitoring and biomarkers of CV and renal risk will be measured in a subset of patients. Physical exams, vital signs, height, weight, waist and hip circumference measurements, ECG, and labs (CBC and blood chemistry at every visit; HbA1c, lipid profile, pregnancy test less frequently), EQ-5D (Quality of Life) questionnaire at all phase 2 visits, and neuropathy assessments at baseline and every 2 years will be done.
Data Analysis: The primary analysis model will be a Cox proportional hazards model with treatment assignment and two stratifying factors (CV disease history and baseline albuminuria) as covariates. Subgroup analyses are planned.
Findings and results: Study enrollment is complete; 22 patients were randomized at NY Harbor and 8606 patients have been randomized at all participating sites. There are no findings, but a study design paper was electronically published (Nephrology Dialysis Transplantation January 14, 2009). 424 patients reached a primary endpoint by October 2010; the first efficacy interim analysis will include 540 patients who reached a primary endpoint.
Study contact: Lois Katz, MD