Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Multicenter, Randomized, Prospective, Double-blind Study to Evaluate the Nephroprotective Effect of Delapril Alone or Combined With Manidipine in Patients With Type 2 Diabetes
Brief Summary: Diabetes mellitus is one of the most common diseases globally, and is considered epidemic in many developed and newly industrialized nations. Diabetes mellitus represents the single largest cause of end-stage renal disease in the U.S. and Europe. At the same time, the primary cause of early death in diabetic patients are cardiovascular complications. Experimental and clinical studies found that angiotensin converting enzyme inhibitors (ACEi) and calcium channel blockers (CCBs) have a specific renoprotective effect and that this effect can be magnified when the two drugs are used in combination. To formally test this hypothesis we designed the Delapril and Manidipine for Nephroprotection in Diabetes (DEMAND) study, a prospective, randomized, double blind trial aimed to compare the effect of 3 years treatment with the ACEi Delapril (30 mg/day), alone or combined to the CCB Manidipine (10 mg/day), versus conventional (non ACEi, non CCB) therapy on the rate of renal function loss and on the incidence of major cardiovascular events in 342 normo- and micro-albuminuric hypertensive type 2 diabetic patients.


Options:
A: 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.
B: Inclusion Criteria:

1. Patients diagnosed with non-dialysis CKD at the enrollment and randomization eGFR≥ 30 ml/min per 1.73 m2 at the enrollment and randomization SBP\> 130 mmHg and/or DBP \> 80 mmHg at the enrollment and randomization. Patients could not receive more than two antihypertensive medications prior to our enrollment, and should discontinue the prior antihypertensive medications after the enrollment according to the investigators' advice.
2. 24 h proteinuria \< 1.5g at the enrollment
3. Patients who signed the informed consent form
4. Baseline serum Cr \< 3 mg/dL at the enrollment and randomization

Exclusion Criteria:

1. Hypertensive crisis (SBP \> 180 mmHg and/or DBP\>110 mmHg)
2. Refractory hypertension (taking \> 2 antihypertensive drugs more than a month, SBP still \> 160mm Hg or DBP \> 100mmHg)
3. Baseline serum Cr \> 3 mg/dl, or kidney transplantation
4. Patients diagnosed as severe cardiac arrhythmia (severe extra beats, supraventricular tachycardias, ventricular arrhythmias, or bradyarrhythmias), heart failure, NYHA \>Ⅲ, angina, stroke, left ventricular hypertrophy or myocardial infarction within 12 months prior to first visit.
5. Patients diagnosed as cancer or severe sepsis
6. Hematological system disorders: myelodysplastic syndrome, granulocytopenia, hypereosinophilic syndrome, polycythemia, thrombocytopenia, and et al.
7. Restrictive pericarditis
8. Systemic Lupus Erythematous
9. Severe diabetes complications such as diabetic ketoacidosis, hyperosmolar coma, retinopathy, amputation, and et al.
10. Patients diagnosed as hyperkalemia(\>5.5mmol/L) within 6 months or at the enrollment
11. Renal artery stenosis or vascular embolism disease
12. Patient is currently pregnant or lactational
13. AST/ALT \> three times of the upper limit of standard value at the baseline
14. Any severe allergy of CCB, diuretic or ACE inhibitor
15. History of severe side effects of CCB, diuretic or ACE inhibitor; long-term use of non-steroidal anti-inflammatory drugs
16. Use of other investigational drugs within 30 days or 5 half-lives of last visit, whichever is longer.
17. Other unsuitable patients judged by the investigators
C: Inclusion Criteria:

* Outpatients aged 65 years or older, and less than 85 years (at the time of informed consent), regardless of sex
* Current antihypertensive treatment with monotherapy
* SBP ≥ 140mmHg or DBP ≥ 90mmHg in a sitting position on two measurements on two clinic visits
* At least one of the following risk factors:

  * Diabetes mellitus Type 2;
  * History of cerebral infarction, cerebral hemorrhage, subarachnoid hemorrhage, or transient ischemic attack (more than 6 months before giving informed consent);
  * Diagnosis of asymptomatic cerebrovascular disease;
  * History of myocardial infarction (more than 6 months before giving informed consent);
  * Diagnosis of angina pectoris or heart failure (New York Heart Association \[NYHA\] functional classification I or II);
  * Diagnosis of left ventricular hypertrophy (thickness of the wall of interventricular septum ≥ 12mm on echocardiography or Sv1+Rv5 ≥ 35mm on electrocardiography before informed consent);
  * Diagnosis of aortic aneurysm;
  * History of aortic dissection (more than 6 months before giving informed consent);
  * Diagnosis of arteriosclerotic peripheral arterial obstruction (Fontaine classification from 2 to 4);
  * Serum creatinine: 1.2-2.5mg/dL (male); 1.0-2.5mg/dL (female);
  * Proteinuria: ≥ +1 (or ≥ 0.3g/g･Cr. estimated from 24-hour urine collection or random urinary protein corrected by urine creatinine).

Exclusion Criteria:

* Secondary hypertension or malignant hypertension
* Heart failure (NYHA functional classification III or IV)
* Required treatment for malignant tumor
* Serious liver or renal dysfunction (serum creatinine \> 2.5mg/dL or with dialysis treatment)
* Not appropriate for change to the test drugs from current therapy for hypertension or coronary diseases (i.e. calcium channel blockers, β-blockers, thiazide diuretics, etc.)
* History of serious adverse drug reactions to angiotensin II receptor blockers or calcium channel blockers
* Patients with other serious reasons (i.e. illness, significant abnormalities, etc.) that investigators judge inappropriate for the study
D: Inclusion Criteria:

* Age ≥ 40 years
* History of diabetes mellitus type 2 for at least three months with stable antidiabetic treatment
* Systolic and/or diastolic blood pressure ≥ 135 or 85 mmHg, respectively. In alternative, antihypertensive therapy regardless of blood pressure values
* Serum creatinine ≤ 1.5 mg/dL
* Urinary albumin excretion rate \< 200 µg/min
* Written informed consent for the trial participation.

Exclusion Criteria:

* Clinical or histological evidence of non-diabetic renal disease, including vascular disease of the kidney, obstructive uropathy, prostatic hypertrophy or incomplete bladder emptying
* Transplanted kidney
* Moderate to severe chronic heart failure (III-IV stage according to the NYHA classification).
* Cerebral hemorrhage, stroke or transient ischemic attack within three months prior to the trial enrolment
* Myocardial infarction within three months prior to the trial enrolment
* Unstable angina pectoris
* Mitral valve stenosis, aortic stenosis or hypertrophic cardiomyopathy
* Secondary (e.g., Cushing disease, phaeochromocytoma, etc.) or severe refractory hypertension
* Poor glycemic control (HbA1c\>11%)
* Connective tissue or autoimmune disease
* Hereditary angioneurotic edema
* Clinically relevant electrolyte imbalance (e.g., serum potassium \> 5.5 mmol/L)
* Clinically relevant hematological disorders
* Anemia with hemoglobin concentrations \< 10 g/dL
* Serious hepatic disease
* Pregnancy or lactating or planning a pregnancy
* Women of childbearing potential without following a scientifically accepted form of contraception
* Any other serious or terminal concomitant disease
* Any condition which may interfere with the absorption of the study treatments
* Any concomitant treatment with ACE inhibitors, angiotensin II blockers, calcium channel blockers, potassium sparing diuretics
* Chronic treatment with nonsteroidal antiinflammatory drugs, antidepressants and neuroleptics, lithium, cimetidine, immunosuppressive and/or antineoplastic drugs, chronic systemic glucocorticoid therapy more than 7 consecutive days in one month, antiarrhythmic drugs (e.g., chinidin, procainamide), anesthetics/narcotics
* History of hypersensitivity to delapril or other ACE inhibitors, manidipine or other dihydropyridine CCBs
* Legal incapacity and/or other circumstances rendering the patient unable to understand the nature, scope and possible consequences of the trial
* Evidence of an uncooperative attitude
* Any evidence that allows predicting that the patient will not be able to complete the trial follow-up.

Answer: D