The Effects of Renin Inhibition on Fibrinolytic Balance and Endothelial Function
Condition: High Blood Pressure
MeSH terms: Hypertension
Intervention: Aliskiren 150 mg; Placebo; HCTZ; Aliskiren 300 mg
Intervention description: Aliskiren 150 mg daily for 2 weeks; Placebo tablet for Aliskerin; HCTZ 25mg every day for 18 weeks; Aliskiren 300 mg for 4 weeks
Phase: Phase 4
Study type: Interventional
Primary purpose: Diagnostic
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Single (Participant)
Enrollment: 31.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: No

Summary:

      Aliskiren (also called TekturnaTM) is a new drug for high blood pressure. Aliskiren works by
      blocking the actions of a substance called renin. Renin is a natural substance in the body
      that raises blood pressure. Renin is believed to contribute to the production of blood clots
      by increasing the amount of a substance known as Plasminogen Activator Inhibitor or PAI-1.
      This study will measure how aliskiren changes the amount of PAI-1 in the blood depending on
      the time of dosing. The purpose of this study is to find out if it is better to take
      aliskiren in the morning or at night.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Adults 18-65 with hypertension

               -  Hypertension is defined as a systolic blood pressure at screening of ≥ 140, a
                  diastolic blood pressure of ≥ 90, or a preexisting diagnosis of hypertension
                  taking antihypertensive medication. If the subject is on anti-hypertensive
                  medication, they can be included in the study, independent of the screening blood
                  pressure.

        Exclusion Criteria:

          -  Serum potassium > 5.0 mmol/L (at the visit directly preceding Randomization)

          -  History of any cardiovascular event (stroke, TIA, MI, unstable angina, CABG,
             percutaneous coronary intervention, hospitalization due to HF) during the 3 months
             prior to Visit 1 or subsequent to enrollment.

          -  Malignant Hypertension (at Randomization): any patient with SBP > 170 mmHg or DBP >
             120 mmHg

          -  Congestive heart failure NYHA class III and IV

          -  Unstable serum creatinine

          -  Second (II) or third (III) degree heart block without a pacemaker.

          -  Concurrent potentially life threatening arrhythmia or other uncontrolled arrhythmia.

          -  Clinically significant valvular heart disease.

          -  Known renal artery stenosis.

          -  Any surgical or medical condition which might significantly alter the absorption,
             distribution, metabolism, or excretion of the study drugs including, but not limited
             to, any of the following:

          -  History of major gastrointestinal tract surgery such as gastrectomy,
             gastroenterostomy, or bowel resection (patients with previous bariatric surgery > 6
             months prior to Visit 1 are allowed to participate).

          -  Any history of pancreatic injury, pancreatitis or evidence of impaired pancreatic
             function/injury as indicated by abnormal lipase or amylase.

          -  Evidence of hepatic disease as determined by any one of the following: SGPT value
             exceeding 3 x Upper Limit of Normal (ULN) at Visit 1, a history of hepatic
             encephalopathy, a history of cirrhosis, esophageal varices, or a history of portocaval
             shunt.

          -  History of malignancy other than basal cell skin cancer within the past five years.

          -  Any concurrent life threatening condition with a life expectancy less than 2 years.

          -  History or evidence of drug or alcohol abuse within the last 12 months.

          -  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.

          -  History of hypersensitivity to any of the study drugs or to medications belonging to
             the same therapeutic class as the study drugs as well as known or suspected
             contraindications to the study drugs.

          -  History of noncompliance to medical regimens or unwillingness to comply with the study
             protocol.

          -  Use of other investigational drugs at the time of enrollment, or within 30 days or 5
             half-lives of enrollment, whichever is longer

          -  Any condition that in the opinion of the investigator would jeopardize the evaluation
             of efficacy or safety.

          -  Persons directly involved in the execution of this protocol.

          -  Pregnant or nursing (lactating) women

          -  Transmeridian travel in the past 6 months

          -  Screening physical and lab findings consistent with the AHA/ADA metabolic syndrome
             criteria (3 of the following: BP ≥ 130/85 or on antihypertensive medications, waist
             size > 40" (m) > 35" (f), Fasting Glucose ≥ 100 mg/dl, Triglycerides ≥ 150 mg/dl, HDL
             <40 mg/dl (m) <50 mg/dl (f))

          -  Smoking