effects of aliskiren, irbesartan, and the combination in hypertensive patients with type 2 diabetes and diabetic nephropathy

Conditions: Diabetes Type 2

Summary: this study will assess the reno-protective effect of renin inhibition with aliskiren as an alternative to irbesartan in type 2 diabetes patients with incipient/overt diabetic nephropathy.

antiproteinuric effects of aliskiren (renin inhibitor), irbesartan (angiotensin receptor antagonist) and the combination in hypertensive patients with type 2 diabetes and incipient/overt diabetic nephropathy

Eligibility criteria:
inclusion criteria: * male and/or female subjects between the ages of 30-80 years with a diagnosis of type 2 diabetes (world health organization criteria) * body mass index (bmi) within the range of 20 and 32. * incipient or overt diabetic nephropathy (urinary albumin excretion ≥ 100 but ≤ 2000 mg/day). * glomerular filtration rate (gfr) ≥ 40 ml/min documented in the last 4 months prior to randomization * to be eligible for randomization, patients must fulfill the following criteria: 1. patients on ongoing hypertensive therapy must have a blood pressure ≥ 135/85 mmhg but lower than 170/105 mmhg at visit 2 (day -1) and patients must be on stable antihypertensive medications for at least 8 weeks prior to visit 2 (run-in period). 2. newly diagnosed hypertensive patients must have a blood pressure ≥ 135/85 mmhg but lower than 170/105 mmhg at visit 2 (day -1). * patients must be on stable hypoglycemic medications for at least 8 weeks prior to visit 2 (day -1). * patients must be willing and medically able to discontinue all angiotensin-converting enzyme inhibitor (acei), angiotensin receptor blocker (arb), aldosterone receptor antagonist and potassium sparing diuretic medications for the duration of the study. * female patients must be postmenopausal, have had a bilateral oophorectomy, or have been surgically sterilized or hysterectomized at least 6 months prior to screening. * oral body temperature within the range of 35.0-37.5 °c * able to provide written informed consent prior to study participation. * able to communicate well with the investigator and comply with the requirements of the study. exclusion criteria: * severe hypertension, grade 3 world health organization (who) classification (mean sitting diastolic blood pressure \[msdbp\] ≥ 110 mmhg and/or mean sitting systolic blood pressure \[mssbp\] ≤ 180 mmhg) * acetylsalicylic acid (asa) treatment \> 1 g/day or regular use of nonsteroidal anti-inflammatory drugs (nsaids) * kidney disease not caused by diabetes or hypertension * serum potassium \ 5.1 meq/l * gfr \< 40 ml/min/1.73m2 as measured by the modification of diet in renal disease (mdrd) formula * serum albumin \< 2.0 mg/dl * history of hypertensive encephalopathy or cerebrovascular accident in the last 12 months prior to visit 1 * transient ischemic cerebral attack during the 6 months prior to visit 1 * current diagnosis of heart failure (new york heart association \[nyha\] class ii-iv) * history of myocardial infarction, unstable angina pectoris, coronary bypass surgery, or any percutaneous coronary intervention (pci) during the 6 months prior to visit 1 * second or third degree heart block without a pacemaker * concurrent potentially life threatening arrhythmia or symptomatic arrhythmia * clinically significant valvular heart disease * type 1 diabetes mellitus * uncontrolled type ii diabetes mellitus; hemoglobin subtype a1c (hba1c) \> 11% * history of malignancy including leukemia and lymphoma (but not basal cell skin carcinoma) within the past five years * participation in any clinical investigation within 4 weeks prior to dosing or longer if required by local regulation. * donation or loss of 400 ml or more of blood within 8 weeks prior to dosing. * significant illness within the two weeks prior to dosing. * any surgical or medical condition which might significantly alter the absorption, distribution, metabolism, or excretion of study drugs including, but not limited to, any of the following: * history of major gastrointestinal tract surgery such as gastrectomy, gastroenterostomy, or bowel resection * currently active or previously active inflammatory bowel disease during the 12 months prior to visit 1 * currently active gastritis, duodenal or gastric ulcers, or gastrointestinal/rectal bleeding during the 3 months prior to visit 1. * any history of pancreatic injury, pancreatitis or evidence of impaired pancreatic function/injury as indicated by abnormal lipase or amylase * evidence of hepatic disease, a history of hepatic encephalopathy, a history of esophageal varices, or a history of portacaval shunt * current treatment with cholestyramine or colestipol resins * history of immunocompromise, including a positive test result. * history of a positive hepatitis b surface antigen (hbsag) or hepatitis c test result. * history of drug or alcohol abuse within the 12 months prior to dosing. * persons directly involved in the execution of this protocol. * any condition that, in the opinion of the investigator or the novartis medical monitor, would jeopardize the evaluation of efficacy or safety * history of noncompliance to medical regimens or unwillingness to comply with the study protocol * known or suspected contraindications to the study medications, including history of allergy to ace inhibitors and/or to thiazide diuretics or other sulfonamide derived drug * any surgical or medical condition, which in the opinion of the investigator, may place the patient at higher risk from his/her participation in the study, or is likely to prevent the patient from complying with the requirements of the study or completing the study * use of any prescription drug or over-the-counter (otc) medication which is prohibited by the protocol. * patients who previously participated in any aliskiren study. other protocol-defined inclusion/exclusion criteria may apply.

Keywords: placebo-controlled study assess the renoprotective effect of renin inhibition aliskiren as an alternative to irbesartan type 2 diabetes patients incipient/overt diabetic nephropathy