Please select the eligibility criteria that correspond to the clinical trial below.
Title: Increasing Stay-on-therapy in Hypertensive Patients Treated With First-line Diuretics: An Active Pharmacosurveillance and Pharmacogenetic Study.
Brief Summary: Background: The use of thiazide diuretics in the treatment of hypertension (HT) is widely considered a first line treatment, given the efficacy and low cost of this class of drugs. This indication is not unanimous, because thiazides can cause metabolic alterations and other side effects increasing cardiac and cerebrovascular risk, which reduce compliance to treatment and increase health care system cost. However, large intervention trials in HT suggest that the improvement in cardiovascular prognosis of HT patients depends more on follow-up procedures than on type of drug used. Furthermore, the investigators have documented improved compliance to antihypertensive therapy by implementing cooperation between general practitioners (GPs) and HT specialists.

Objectives: In a multicenter, open label randomized study the investigators will compare the persistence on therapy of thiazides versus other treatments, as a first line antihypertensive therapy, in a clinical setting characterized by a strict cooperation between GPs and HT specialist. The investigators will also analyse candidate genes with impact on drug-induced metabolic alterations to elucidate the pathophysiology of these phenomena.

Methods: 260 GPs will recruit 2600 hypertensive patients with indication to pharmacological treatment and randomise them to starting treatment with chlortalidone (12.5 to 25 mg daily, 1300 pts) or a GP decided single drug (excluding thiazides) or combination therapy at highest tolerated dose. In both groups any other class of antihypertensive drugs can be added over time in order to achieve blood pressure control (\<140/90 mmHg). Follow-up will last 2 years. Blood sample and urine analyses, carotid and cardiac ultrasound will be performed at baseline and scheduled time points. Genotyping will be performed by sequencing. Data will be collected and stored using a web based centralized Case Report Form (CRF) Expected results: Results will highlight whether a follow-up strategy based on tight cooperation between GPs and HT specialists can allow the use of thiazides as first line antihypertensive therapy without any negative effect on persistence, adherence and efficacy of the treatment. These data can be used to reduce total burden of the Health Care System in HT by replacing more expensive drugs with diuretics in the 50% of hypertensive patients, who do not receive this class of drugs. Furthermore, the pharmacogenetic approach may clarify the pathophysiological mechanisms of drug-induced metabolic side effects


Options:
A: Inclusion Criteria:

* Patients with essential hypertension

Exclusion Criteria:

* Severe hypertension
* History or evidence of a secondary form of hypertension
* History of myocardial infarction.
* Other protocol-defined inclusion exclusion criteria also apply.
B: Men and women hypertensive patients, ages 55 and above. A total of 36 percent were diabetics.
C: Inclusion Criteria:

* At least 55 years of age.
* Previously untreated or treated hypertension.
* For patients \>= 60 years, evidence of at least one CV disease or target organ damage, or for patients 55-59 years evidence of at least two CV diseases or target organ damage from two different organ systems as defined in the protocol.

Exclusion Criteria:

* Allergy to any of the drugs administered in this trial.
* Current angina pectoris (ie, no anginal event requiring NTG within 1 month prior to Visit 1).
* Secondary hypertension.
* Refractory hypertension defined as SBP \>= 180 mmHg and/or DBP \>= 110 mmHg unresponsive to triple-drug regimens of sympatholytics, diuretics and vasodilators.
* History of symptomatic heart failure (NYHA classes II-IV) or ejection fraction \< 40%.
* Myocardial infarction, coronary revascularization (CABG or PCI), unstable angina within one month of Visit 1.
* Stroke or transient ischemic event (TIA) within 3 months of Visit 1.
* Significant obstructive valvular cardiovascular disease or any valvular disease expected to lead to surgery during the course of the study.
* Evidence of hepatic disease (AST or ALT values \>= 2 X upper limit of normal).
* Impaired renal function (serum creatinine \>= 2.5 mg/dL (221 µmol/L)).
* Baseline serum potassium of \> 5.2 meq/L not on potassium supplements.
* History of malignancy including leukemia and lymphoma (but not basal cell skin cancer) within the last 5 years.
* History of clinically significant auto immune disorders such as Systemic Lupus Erythematosus.
* Significant non-cardiovascular illness or condition likely to result in death prior to trial completion, e.g., major organ transplant (life expectancy \<5 years).
* Significant cardiovascular disease such as an aortic aneurysm ≥ 6 cm, likely requiring surgical intervention during the course of the study.

Other protocol-defined exclusion criteria applied to the study.
D: Inclusion Criteria:

* Hypertensive patients will be 18 to 75-year old.
* Eligible patients will be asked for written informed consent and thereafter referred to the identified Hypertension Specialist Centre located in their areas, for end-organ damage evaluation by echocardiography, carotid ultrasound and urine dip-stick.
* Eligible patients are required to have stage Ic or II essential hypertension, and to be previously untreated or poorly controlled. They will be selected by GPs participating into the study. Similar to untreated patients, those with poor control of blood pressure under multiple-drug therapy will start treatment with one single drug, which will be titrated to the highest dose before adding subsequent medications, based on the GP's judgement.
* Hypertension will be defined according to 2003 ESH/ESC guidelines (1). Blood and urine tests will be performed, according to guidelines for Hypertension Management For General Practitioners (GP) of the Regione Campania (see BURC number 11, 18/02/2002). This screening includes cell blood counts (CBCs), serum creatinine, sodium, potassium, uric acid, total cholesterol, triglycerides, HDL-cholesterol, glucose, urine analysis and EKG. LDL will be calculated starting from the total cholesterol, triglyceride and HDL-cholesterol.

Exclusion Criteria:

* Omen in fertile age not using recognized contraceptive methods, or pregnant or nursing will be excluded from the protocol, since the use of many antihypertensive drugs is contraindicated in pregnancy and lactation.
* Patients will be excluded when presenting with documented coronary or cerebrovascular events in the previous 6 months, NYHA class higher than 1
* History of congestive heart failure
* Secondary hypertension
* Cancer disease
* Renal disease (serum creatinine \>2 mg/dl)
* Liver cirrhosis or severe dysfunction, or any other health problem that may interfere with the projected 2 year follow-up.

Data will be stored in an electronic database located in the Coordinating Centre, to which GPs may have access for uploading data on a daily base, using personal, encrypted, login and password. These data will be stored in the central database. After local echocardiographic evaluation, patients showing left ventricular Ejection Fraction \< 45% will be excluded from the study.

Answer: D