Please select the eligibility criteria that correspond to the clinical trial below.
Title: Phase IV Study for Effect of Intensive Blood-Pressure Control Using Anti-hypertensive Agents in Essential Hypertension With History of Stroke
Brief Summary: 1. Objectives and Hypothesis

   1. Objectives:

      This study evaluates whether strict BP management is useful for the prevention of recurrent stroke.

      Hypertensive patients with history of stroke are treated with stepwise multi-drug therapy to achieve stricter BP target \<120/80 mmHg in the strict BP control group and less stricter BP target \<140/90 mmHg or \<130/80 mmHg for patients with current DM/CKD/MI in the standard BP control group. The participants under the BP treatment achieving their respective BP target will be followed for recurrence of stroke. The study continues until the number of patients with the first recurrent stroke reaches a total of 330 between the two groups. The occurrence rates of recurrent stroke will be compared between the two groups.
   2. Hypotheses The incidence of recurrent stroke will be lower in a strict BP control group having lower BP target: \<120/80 mmHg\* than in a standard BP control group having BP target \<140/90 mmHg or \<130/80 mmHg for current DM/CKD/MI in patients with hypertension.
2. Study design This will be a multicenter, randomized, open-label study. The study consists of a screening period, a titration period and a follow-up period. The screening period is a period between the date of consent and the enrollment date. Hypertensive patients with history of stroke are randomly assigned to either the strict BP control group having the target of \<120/80 mmHg or the standard BP control group having the target of \<140/90 mmHg without current DM, CKD or MI and \<130/80 mmHg with current DM, CKD or MI. The titration period is the period finding a treatment which achieves target BP, and 24 weeks at maximum. Patients will be treated with stepwise multi-drug therapy using an angiotensin-receptor antagonist, diuretic, calcium channel blocker and aldosterone antagonist. The participants will be observed under the BP management for their respective BP target. The study will be continued until the number of patients with the first recurrent stroke reaches a total of 330 between two groups. The follow-up period will be 3 years.

The recurrent rates of stroke in both groups will be compared from various aspects, and strict BP management will be investigated on the usefulness in prevention of recurrent stroke.


Options:
A: Inclusion Criteria:

* Qualifying event: stroke or TIA 1 to 6 months previous to randomization.
* All patients should have a CT scan or MRI (preferably MRI) at screening. The CT scan or MRI carried out at the time of the qualifying event, if available, is acceptable. Stroke will be defined as imaging evidence of a recent brain infarction (or haemorrhage) independently of duration of clinical symptoms, or as duration of clinical symptoms \> 24 h even in absence of imaging evidence of lesion
* TIA as clinical symptoms (involving limbs or speech) lasting \< 24 h without imaging evidence of infarction. Enrolling units should avoid enrolling patients with TIA in a proportion greater than 25% of enrolled patients. The general coordinators in Milan and Beijing may decide stopping enrolment of TIA patients if their proportion is becoming greater than expected.
* A haemorrhagic stroke (1 to 6 months previously) is also a qualifying event, but only for the BP-lowering component of the trial (see Exclusion criteria).
* Age: 65 years and above. No fixed upper age limit is introduced, but frail patients aged above 80 years should not be enrolled.
* Gender: either gender.
* BP: Only hypertensive patients: untreated patients with SBP ≥140 mmHg; patients on antihypertensive treatment with any BP (but see exclusion criteria)
* LDL-C: Patients without statin treatment with LDL-C \> 2.8 mmol/l; patients on statin treatment with any LDL-C value (but see exclusion criteria)
* Antiplatelet therapy: All patients should be under antiplatelet therapy (agents and doses chosen by the investigator according to accepted guidelines), unless contraindicated. Anticoagulant (instead of antiplatelet) therapy whenever indicated (e.g. atrial fibrillation).

Exclusion Criteria:

* Qualifying event:

  1. Patients in unstable clinical conditions
  2. Clinical disturbances caused by non-stroke pathology
  3. patients with haemodynamically significant carotid stenosis or requiring carotid revascularization
  4. haemorrhagic stroke is an exclusion criterion for the lipid lowering component of the trial; however, these patients should be randomized to the BP component, but considered in addition to the number of patients requested to each enrolling unit, in order not to decrease the power of the lipid-lowering component.
* BP: - known secondary hypertension;
* SBP \>140 mmHg under three antihypertensive drugs at full doses (these patients are unlikely to achieve SBP \< 125 mmHg, if so randomized);
* orthostatic hypotension (SBP fall \> 25 mmHg on standing);
* LDL-C: - LDL-C \>2.8 mmol/l under full dose of a statin (these patients are unlikely to achieve LDL-C targets).
* LDL-C \> 4.5 mmol/l under low dose of a statin or untreated (these patients are unlikely to achieve the lower LDL-C target).
* Others: - Patients with a myocardial infarction (preceding or subsequent to the qualifying stroke or TIA) if their baseline LDL-C is \< 1.8 mmol/l
* Dementia
* Severe disability (modified Rankin scale \> 4)
* Severe chronic renal failure defined as serum creatinine \> 250 micromol/l
* Hepatic disease as determined by either AST or ALT values \> 2 times the upper limit of normal
* History of hepatic encephalopathy, esophageal varices or portocaval shunt
* History of gastrointestinal surgery or disorders which could interfere with drug absorption
* Known allergy or contraindications to one of the drugs to be administered in the study
* History of malignancy including leukaemia and lymphoma (but not basal cell skin cancer) within the last 5 years
* History of clinically significant autoimmune disorders such as systemic lupus erythematosus
* History of drug or alcohol abuse within the last 5 years
* History of non-compliance to medical regimens and/or patients who are considered potentially unreliable
* Inability or unwillingness to give free informed consent
B: Inclusion Criteria:

Participants include those with essential hypertension and history of stroke who satisfy the following criteria:

* Outpatient
* Onset of stroke(cerebral infarction/cerebral hemorrhage) occurred between 30 days and 3 years prior to the date of consent.
* Drug adherence is ≧80% during the screening period.
* Mean of 2 baseline BP measurements(measured at outpatient clinic) within 30 days prior to the date of consent is either 180 \>SBP ≧130 mmHg or 110 \>DBP ≧80 mmHg (untreated -3 anti hypertensive agents patients).
* Cerebral infarction with severity 3 or less in the modified Rankin scale.

Exclusion Criteria:

Patient who meets any one of the following criteria is excluded from the study.

* Women who are pregnant, are possible pregnant, or are breastfeeding
* Possible secondary hypertension
* Severe hypertension (grade III or greater) with baseline SBP ≧180 mmHg or DBP ≧110 mmHg)
* Myocardial infarction or undergoing angioplasty occurred within 3 months prior to the screening.
* Current or previous heart failure with NYHA classification class III or more, or EF less than 35%
* Severe bilateral carotid stenosis or major cerebral artery occlusion
* Severe paralysis due to stroke (modified Rankin scale ≧ 4 )
* Current renal dysfunction (serum Cr ≧ 2.0 mg/dL right before the date of consent)
* Current hepatic dysfunction with AST or ALT value ≧ 100 IU/mL right before the date of consent
* Refractory hypertension treated with four or more antihypertensive drugs
* Hypersensitivity or allergy to losartan and other angiotensin II receptor blockers, hydrochlorothiazide, amlodipine or sulfonamide derivative
* Major surgery planned during the study period
* Participants of other clinical studies within the last 30 days
* Current malignancy (previous malignancy within 5 years after the end of treatment) excluding squamous-cell skin cancer
* Previous and current subarachnoid hemorrhage
* Definitive dementia 12) (based on a clinical diagnosis)
* Patients who have difficulty in signing consent or who do not agree to the provided consent
* Patients who are judged to be unsuitable for participating the study by the primary investigator or sub-investigator.
C: Inclusion Criteria:

1. Men and women aged ≥50 years;
2. Diabetes defined as:

   * A self-reported previous diagnosis by health care professionals and taking anti-diabetic medications;
   * Fasting plasma glucose level of ≥126 mg/dL (7.0 mmol/L). Fasting is defined as no caloric intake for at least 8 hours;
   * 2-hour plasma glucose level of ≥200 mg/dL (11.1 mmol/L) during an oral glucose tolerance test. The test should be performed using a glucose load containing the equivalent of 75 g anhydrous glucose dissolved in water; or
   * HbA1c concentration of ≥6.5% (48 mmol/mol);
3. Systolic blood pressure

   -≥140 mmHg on 0 medication;
   * 130-180 mmHg on 1 medication;
   * 130-170 mmHg on up to 2 medications;
   * 130-160 mmHg on up to 3 medications; or
   * 130-150 mmHg on up to 4 medications;
4. Increased risk of cardiovascular disease (one or more of the following):

   * Previous history of clinical CVD (≥ 3 months)
   * Subclinical CVD within 3 years
   * 2 or more CVD risk factors
   * Estimated glomerular filtration rate (eGFR) 30-59 ml/min/1.73 m2

Exclusion Criteria:

1. History consistent with type 1 diabetes
2. Known secondary cause of hypertension
3. One minute standing systolic BP \<110 mmHg
4. Arm circumference too large to allow accurate blood pressure measurement with available devices
5. Cardiovascular event or procedure or hospitalization for unstable angina within the past 3 months
6. Symptomatic heart failure within the past 6 months or left ventricular ejection fraction (by any method) \<35% within the past 6 months
7. ALT or AST levels more than twice the upper limit of the normal range or active liver diseases
8. Dialysis, kidney transplantation, eGFR \<30 ml/min/1.73 m2, or serum creatinine \>2.0 mg/dl
9. Proteinuria
10. Previous diagnosis of polycystic kidney disease or glomerulonephritis
11. A medical condition likely to limit survival to less than 5 years
12. Any factors judged by the clinic team to be likely to limit adherence to interventions
13. Failure to obtain informed consent from participant
14. Currently participating in another intervention study
15. Currently living with another BPROAD participant
16. Pregnancy, currently trying to become pregnant, or of child-bearing potential and not using birth control
D: Inclusion Criteria:

* Men and women aged ≥40 years
* A history of symptomatic, MRI/CT-confirmed ischemic stroke (3-12 months since last acute onset)
* Systolic BP ≥140 mmHg on 0 medication; 135-180 mmHg on 1 medication; 135-170 mmHg on up to 2 medications; 135-160 mmHg on up to 3 medications; or 135-150 mmHg on up to 4 medications

Exclusion Criteria:

* Documented symptomatic intracranial and/or extracranial stenosis (≥50%), or asymptomatic intracranial and/or extracranial stenosis (≥70%)
* Disabling stroke (modified Rankin score of ≥4)
* Previous intracranial hemorrhage from a non-traumatic cause
* Any symptoms of orthostatic hypotension during the standing BP measurement, or standing systolic BP \<110 mmHg
* Severe heart failure (NY Heart Association class III and IV) within the past six months or left ventricular ejection fraction (by any method) \<35%
* Any history of atrial fibrillation, ventricular aneurysm, or suspicion of cardioembolic pathology for stroke
* Other specific cause of stroke identified by routine clinical care (e.g., arteritis, dissection, migraine/vasospasm, drug abuse)
* Dialysis, eGFR \<20 ml/min/1.73 m2, urine protein-to-creatinine ratio ≥1 g/g, or albumin-to-creatinine ratio ≥ 600 mg/g
* Planned or probable revascularization (any angioplasty or vascular surgery) within three months after screening
* A medical condition likely to limit survival to less than three years
* A cancer diagnosed and treated within the past two years that, in the judgment of clinical study staff, would compromise a participant's ability to comply with the protocol and complete the trial (except non-melanoma skin cancer, early-stage prostate cancer, or localized breast cancer)
* Any factors judged by the clinic team to be likely to limit adherence to the intervention
* Failure to obtain informed consent from a participant
* Currently participating in another intervention study
* Pregnant, currently trying to become pregnant, or of child-bearing potential and not using birth control

Answer: B