Effects of Aliskiren, Irbesartan, and the Combination in Hypertensive Patients With Type 2 Diabetes and Diabetic Nephropathy
- Conditions
- Diabetes Type 2
- Registration Number
- NCT00464880
- Lead Sponsor
- Novartis
- Brief 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.
- Detailed Description
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
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 24
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Male and/or female subjects between the ages of 30-80 years with a diagnosis of type 2 diabetes (World Health Organization criteria)
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Body mass index (BMI) within the range of 20 and 32.
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Incipient or overt diabetic nephropathy (urinary albumin excretion ≥ 100 but ≤ 2000 mg/day).
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Glomerular filtration rate (GFR) ≥ 40 ml/min documented in the last 4 months prior to randomization
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To be eligible for randomization, patients must fulfill the following criteria:
- 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).
- Newly diagnosed hypertensive patients must have a blood pressure ≥ 135/85 mmHg but lower than 170/105 mmHg at Visit 2 (Day -1).
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Patients must be on stable hypoglycemic medications for at least 8 weeks prior to Visit 2 (Day -1).
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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.
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Female patients must be postmenopausal, have had a bilateral oophorectomy, or have been surgically sterilized or hysterectomized at least 6 months prior to screening.
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Oral body temperature within the range of 35.0-37.5 °C
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Able to provide written informed consent prior to study participation.
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Able to communicate well with the investigator and comply with the requirements of the study.
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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)
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Acetylsalicylic acid (ASA) treatment > 1 g/day or regular use of nonsteroidal anti-inflammatory drugs (NSAIDs)
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Kidney disease not caused by diabetes or hypertension
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Serum potassium < 3.5 or > 5.1 mEq/L
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GFR < 40 ml/min/1.73m2 as measured by the Modification of Diet in Renal Disease (MDRD) formula
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Serum albumin < 2.0 mg/dL
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History of hypertensive encephalopathy or cerebrovascular accident in the last 12 months prior to Visit 1
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Transient ischemic cerebral attack during the 6 months prior to Visit 1
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Current diagnosis of heart failure (New York Heart Association [NYHA] Class II-IV)
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History of myocardial infarction, unstable angina pectoris, coronary bypass surgery, or any percutaneous coronary intervention (PCI) during the 6 months prior to Visit 1
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Second or third degree heart block without a pacemaker
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Concurrent potentially life threatening arrhythmia or symptomatic arrhythmia
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Clinically significant valvular heart disease
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Type 1 diabetes mellitus
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Uncontrolled type II diabetes mellitus; hemoglobin subtype A1C (HbA1C) > 11%
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History of malignancy including leukemia and lymphoma (but not basal cell skin carcinoma) within the past five years
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Participation in any clinical investigation within 4 weeks prior to dosing or longer if required by local regulation.
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Donation or loss of 400 mL or more of blood within 8 weeks prior to dosing.
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Significant illness within the two weeks prior to dosing.
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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
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History of immunocompromise, including a positive test result.
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History of a positive hepatitis B surface antigen (HBsAg) or hepatitis C test result.
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History of drug or alcohol abuse within the 12 months prior to dosing.
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Persons directly involved in the execution of this protocol.
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Any condition that, in the opinion of the investigator or the Novartis medical monitor, would jeopardize the evaluation of efficacy or safety
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History of noncompliance to medical regimens or unwillingness to comply with the study protocol
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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
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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
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Use of any prescription drug or over-the-counter (OTC) medication which is prohibited by the protocol.
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Patients who previously participated in any aliskiren study.
Other protocol-defined inclusion/exclusion criteria may apply.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- CROSSOVER
- Primary Outcome Measures
Name Time Method To investigate whether renin-inhibition using aliskiren 300 mg daily could be a treatment alternative to the angiotensin II receptor antagonist irbesartan 300 mg with an equivalent potential for reno-protection
- Secondary Outcome Measures
Name Time Method To investigate whether combination therapy using aliskiren 300 mg daily and irbesartan 300 mg daily has a greater effect on reno-protection than either drug alone To investigate whether aliskiren, irbesartan or the combination reduce biomarkers of inflammation and cardiovascular risk
Trial Locations
- Locations (1)
Novartis
🇩🇰Gentofte, Denmark