Aliskiren vs Hydrochlorothiazide in Hypertensive Type II Diabetic Patients on Resistance Arteries

Launched by SIR MORTIMER B. DAVIS - JEWISH GENERAL HOSPITAL · Nov 24, 2011

Keywords

ClinConnect Summary

No description provided

Gender

ALL

Eligibility criteria

• Inclusion Criteria:
• • Hypertensive Group
• • Diabetes mellitus (diagnosed for at least 6 months) will be defined by usual criteria based on basal glycemia or glucose tolerance test . Diabetes must be well controlled, with glycosylated hemoglobin below 0.08 (8%).
• • Hypertension is defined as a mean SiSBP \> 130 mmHg or SiDBP of 85-115mmHg at the screening visit, and after two weeks of placebo therapy. (Hypertension will be considered essential if there is no evidence of an underlying treatable cause after suitable clinical and laboratory assessment. Hypertensive patients may be taking any antihypertensive agent except a renin inhibitor. They may be taking an ACE inhibitor or an ARB, which will not be discontinued. If they have been on HCTZ, they are eligible to participate.
• • Subjects are 30-70 years old
• • Informed Consent obtained by patient
• • Criteria for inclusion: Control Group
• • Diabetic defined as: hemoglobin A1C \< 0.06 ( 6%) and / or fasting glycemia \< 5.6mmol/L.
• • Hypertensive defined as : SiSBP ≤120 mmHg and/or SiDBP ≤80mmHg
• • Subjects are 30-70 years old
• • Informed Consent obtained by patient
• Exclusion Criteria:
• • Uncontrolled diabetes ( defined as: preprandial glycemia usually above 10 mmol/L and glycosylated hemoglobin above 0.08).
• • Renovascular hypertension
• • History of malignant hypertension
• • Sitting systolic blood pressure \> 210 mmHg
• • Cerebrovascular accident within the past year, or current transient ischemic attacks
• • History of myocardial infarction, percutaneous coronary angioplasty or coronary artery bypass surgery
• • Clinically significant AV conduction disturbances and/or arrhythmias (e.g. second- or third-degree AV block; Sick-sinus syndrome or clinically significant bradycardia- resting heart rate \< 45 beats/minute).
• • Tachyarrhythmias; clinically significant arrhythmias
• • Presence of an accessory bypass tract (e.g. Wolff-Parkinson-White syndrome)
• • Angina pectoris
• • Current or prior history of heart failure or known left ventricular ejection fraction ≤ 40%
• • History of unexplained syncope or a known syncopal disorder (e.g., Stokes-Adams Syndrome)
• • Presence or known history of hemodynamically significant obstructive valvular disease or hypertrophic cardiomyopathy
• • Hypertensive patients already taking a renin inhibitor.
• • Concomitant treatment
• • Psychotropic or Antidepressant Agents
• • Major psychotropic agents such as phenothiazines are not permitted. Chronic doses of antidepressants are not permitted.
• • Oral Contraceptives are not allowed if the patient's hypertension was induced by this medication.
• • Regular use of NSAID is permitted if taken regularly on a stable regimen. Aspirin in small doses (≤ 1 g/day) as a cardioprotective agent is permitted. Acetaminophen is permitted.
• • Other Drugs
• • Concomitant use of oral or inhaled steroids, ACTH, immunosuppressants or lithium are not allowed, nor are cyclosporine, quinidine, aliskiren available from the market.
• • Laboratory Parameters
• • Glycosylated hemoglobin above 0.08 (8%).
• • Plasma creatinine concentration ≥ 200 μmol/L (adjusted for age and weight).
• • Prior to patient entry, any hematuria should be evaluated, the etiology established/documented, and treatment rendered as appropriate.
• • Off-treatment serum potassium concentration ≥ 5.5 mmol/L or ≤ 3.5 mmol/L
• • AST (SGOT) or ALT (SGPT) \> 2 x normal upper limit, and if clinically significant
• • Clinically significant laboratory values outside of the established normal range including but not limited to any of the following parameters: hematocrit, hemoglobin, platelet count or white blood cell count
• • Allergies/Hypersensitivity /Pulmonary
• • Known hypersensitivity or contraindication to aliskiren or thiazide diuretics.
• • History of clinically important malabsorption or gastrointestinal resection.
• • Smoking of 10 cigarettes or more is excluded. Also excluded are co-existent conditions which could independently affect the histology of resistance vessels except for diabetes (e.g. any disease which may be associated with vasculitides: collagen-vascular diseases, chronic hepatitis B antigenemia, circulating immune complexes, complement disorders, amyloidosis, scleroderma, etc.).
• • Pregnancy or lactating females. Females of childbearing age who are not surgically sterilized and who are using effective contraception may enter only if an exclusionary pregnancy test is done within 72 hours of the first double-blind dose of test agent. Pregnancy tests will then be done monthly throughout the study in women capable of conception.
• • Other concurrent severe disease which could preclude participation or survival, such as neoplasm or Acquired Immunodeficiency Syndrome (AIDS), or patients known to be HIV positive.
• • Any known bleeding or platelet disorder.
• • The known absence of one kidney.
• • Patients who are currently abusing or previously abused alcohol or other drug substances (within past two years).
• • Mentally or legally incapacitated patients.
• • Patients who have participated in another investigational drug trial, including those using marketed drugs (i.e. patient has signed a consent form), within the 28 days prior to start of placebo therapy.
• • Patients who, in the opinion of the investigator, will not cooperate fully, keep appointments or are generally unreliable.
• • Inability or unwillingness on the part of the patient to sign the Patient Consent Form.
• • Phase V of Korotkoff sounds cannot be detected.