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

Summary

This is competitive enrollment trial an dour center plan to enroll 60 subjects of the 8600 patients.

Screening: 4-wk to 12-wk screening period (Visits1 and 2)
The patient should be on conventional therapy according to national guidelines and relevant to his/her medical history and concomitant conditions. If this is not already the case at the first four weeks of the screening period should be used to stabilize the patient on the aforementioned therapy. If this is not already the case, the first four weeks of concomitant treatment must include a stable anti-hypertension medication dose (e.g.ACEI, ARB, Calcium-channel Blocker, Beta-blocker, Alpha-blocker, diuretics) prior to randomization and antihypertensive treatment must be stable for at least 4 wks prior to randomization.

Randomization and Double-blind study treatment Period:Visit 3
Patients who fulfill all eligibility criteria will be randomized to receive aliskiren 150 mg QD or placebo Q 8 AM on top of their conventional treatment for 4 wks (Visits 3 to 5). The randomization assignment will be done by the sponsor and subjects will have a 50/50 chance to receive the study drug or placebo.

After randomization, patients will be up titrated to aliskiren target dose of 300 mg OD or placebo (Visits 5 to end of study). Patients can be down titrated to aliskiren 150 mg OD or placebo at any time of the study in case of intolerance or other reasons. Throughout the trial investigators should to strive to achieve a BP target ≤135 / 85 mmHg.

Visits 4-8 will take place at 1 to 4 week intervals based on the date Visit 3 was held. The study medication will also be re-supplied at Visits 5 and 8. Three first morning urine samples will also be collected at Visit 8.

Visit 9 to the end of the study will take place every 3 months. The subjects will be asked to bring 3 first morning urine samples collected on 3 consecutive days prior to visits 9, 10, 11, 13, 15, 17, 19, 21. Each urine sample may be stored in a refrigerator until all 3 samples are collected and brought to the research clinic. Questionnaires and vital signs will also be collected at each visit. Once every year, a physical exam will be completed by the study doctor. Urine and blood tests will also be collected to assess the subjects’ progress in the study. At Visit 15, the study medication will be re-supplied and the neuropathy (assessment of circulation, pain and discomfort in the lower extremities) questionnaire will also be completed.

Final Visit:
Total follow-up is estimated to be 4 years. However, the final visit may occur at year 2 or 4 for each individual subject depending on when they first enrolled in the study. The subjects will be asked to return 3 first morning urines, blood will be collected, and physical exam completed by the study doctor and health questionnaires will be completed. At this time, the subjects will be informed that this is their final visit and all study procedures will end on this day.

All subjects will be asked to return their study medications for accountability and compliance at each visit. They will also be assessed for adverse events and hospitalizations.

Unscheduled Visits:

The study doctor my conduct unscheduled visits to re-assess abnormal lab values, adverse events, and blood pressure managements to ensure subjects safety.

Prohibited Medications:, renin-inhibitors, potassium-sparing diuretic, anti depression MOA inhibitors, cholestyramine and colestipol resins, Oral adsorben

Participant Eligibility

1. Patients with type 2 diabetes. Patients have to be either currently treated with oral antidiabetics
and/or insulin, or have to have a documented fasting plasma glucose ≥
7.0 mmol/L (126 mg/dL) or 2-h plasma glucose ≥ 11.1 mmol/L (200 mg/dL)
(WHO 2006a)
2. Male or female patients ≥ 35 years of age.
3. Patients who provide written informed consent to participate in the study after the purpose
and nature of the investigation have been clearly explained to them.
Additional inclusion criteria applicable at Visit 3:
4. Patients with at least one of the following :
• Persistent macroalbuminuria (UACR ≥ 200 mg/g [or 22.6 mg/mmol] in at least two
out of three first morning void urine samples) and an eGFR ≥ 30 mL/min/1.73 m2 as
calculated by the abbreviated MDRD study equation (mean of two consecutive
measurements)
• Persistent microalbuminuria (UACR ≥ 20 mg/g and < 200 mg/g [or UACR
≥ 2.26 mg/mmol and < 22.6 mg/mmol] in at least two of three morning void urines)
and a mean eGFR ≥ 30 and < 60 mL/min/1.73 m2 calculated by the abbreviated
MDRD study equation (Levey, et al 2000) (mean of two consecutive measurements)
• A history of cardiovascular disease and a mean eGFR ≥ 30 and
< 60 mL/min/1.73 m2
History of cardiovascular disease is defined as at least one of the following:
• Previous MI (previous hospitalization with a discharge diagnosis of MI)
• Previous stroke (previous hospitalization with a discharge diagnosis of stroke. A
previous transient ischemic attack -TIA- is not sufficient to fulfill this criterion)
• HF (previous hospitalization with a discharge diagnosis of HF, with or without
preserved ejection fraction)
• Coronary artery disease (CAD) defined as follows:
• History of percutaneous coronary intervention [PCI]
• Coronary artery bypass graft [CABG]
• Angiographically proven stenosis ≥ 50% in at least one major epicardial
coronary artery
5. Patient's concomitant treatment must include an ACEI or an ARB. Patient should be on
conventional therapy according to national guidelines. Patients must not have had any
adjustments to their concomitant antihypertensive therapy for at least four (4) weeks prior
to randomization (Visit 3).