Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Double-Blind, Randomised, Dose Ranging, Multi-Centre, Phase IIIb Study to Evaluate the Efficacy and Safety of High Doses of Candesartan Cilexetil (Atacand®) on the Reduction of Proteinuria in the Treatment of Subjects With Hypertension and Moderate to Severe Proteinuria
Brief Summary: The purpose of this study is to assess the effects of high doses of candesartan cilexetil and also to assess which dose (16mg, 64mg, 128mg) is the most optimal for the maximum reduction of proteinuria.


Options:
A: Inclusion Criteria:

* Patients with mild to moderate hypertension with a mean sitting diastolic blood pressure (MSDBP) \> 85 and \< 110 mmHg for non-treated patients. Previously treated patients with MSDBP \< 110 mmHg. Treated is defined as having taken medication until \< 2 days prior to Visit 1
* Positive urine spot test with Micral dipstick (detection of urinary albumin concentration of at least 50 mg/l) at Visit 1 (day -21).
* Confirmation of MAU of at least 2 out of 3 measurements determined in the first morning urine samples performed at Visit 1 day-21), Visit 2 (day -14) or Visit 3 (day -7). MAU is defined for male patients as urinary albumin creatinine ratio (UACR) \> 2.5 mg/mmol and \< 25.0 mg/mmol and for female patients as UACR \> 3.5 mg/mmol and \< 35.0 mg/mmol at both visits.

Exclusion Criteria:

* Evidence of renal impairment as determined by any one of the following:

  * serum creatinine clearance \< 30 ml/min as determined by Cockroft and Gault formula \[Cockroft and Gault, 1976\] and/or
  * serum creatinine \> 1.25 x ULN at Visit 1,
  * a history of dialysis, or
  * a history of nephrotic syndrome.
* Serum potassium values \<3.5 mmol/l or \>5.5 mmol/l at Visit 1
* Any medical condition which might significantly alter the urinary excretion of albumin

Other protocol-defined exclusion criteria may apply.
B: Inclusion Criteria:

* Creatinine: 150-350 micromol/L
* Blood pressure \> 110 systolic
* Negative pregnancy test for fertile women
* Written and oral informed consent from the patient

Exclusion Criteria:

* Treatment with both ACE-inhibitors (ACE-I) and angiotensin receptor blockers
* Pregnancy or breastfeeding
* Treatment with immunosuppressive medication, steroids or non-steroidal anti-inflammatory drugs (NSAIDs)
* Serious chronic heart failure (New York Heart Association \[NYHA\] III-IV)
* Chronic liver disease
* Suspicion or verified kidney artery stenosis
* Cardiac arrhythmia and/or implanted pacemaker
* Myocardial infarction or cerebrovascular incidence within the last 3 months
* Allergy towards ACE-I or angiotensin receptor blockers
* Amputation of a whole extremity or the crural or femoral part of the leg
* Dementia or a psychological condition that makes understanding of the examination conditions impossible
* Dialysis or renal transplantation
* Treatment with aldosterone antagonists
* Hyperkalemia \> 5.5 mmol/l
* Another serious chronic non-renal disease
C: Inclusion Criteria:

Coronary Artery Disease: Previous Myocardial infarction(\> 2 days prior to informed consent), or stable or previous unstable angina (\> 30 days prior to informed consent) with documented multivessel coronary artery disease or a positive stress test, or multivessel Percutaneous Transluminal Coronary Angioplasty (\> 30 days prior to informed consent), or previous multivessel Coronary Artery Bypass Grafting without angina (if surgery performed \> 4 years prior to informed consent) or with recurrent angina after surgery.

Other High Risk:

1. Peripheral Arterial Disease: Previous limb bypass surgery or angioplasty or amputation, intermittent claudication on history with ankle/arm Blood Pressure ratio \< 0.8 on at least one side, or significant stenosis by angiography or non-invasive testing
2. Previous stroke
3. Transient ischemic Attack \> 7 days and \< 1 year prior to informed consent
4. Diabetes Mellitus (types I or II): with evidence of end-organ damage (retinopathy, Left ventricular hypertrophy, micro or macro albuminuria), or any evidence of previous cardiac or vascular disease.

No definite and specific indication or contraindication for any of the study treatments. Written informed consent.

Exclusion Criteria:

A. Medication use:

1. Inability to discontinue Angiotension Converting Enzyme (ACE) inhibitors or Angiotension 2 receptor antagonists (AIIAs).
2. Patients with known hypersensitivity or intolerance to Angiotension 2 receptor antagonists (AIIAs) or Angiotension Converting Enzyme (ACE)inhibitors.

NOTE: Patients with known intolerance to Angiotension Converting Enzyme inhibitor intolerance ( ACE-I) can be enrolled in the TRANSCEND study.

B. Cardiovascular disease:

1. Symptomatic congestive heart failure.
2. Hemodynamically significant primary valvular or outflow tract obstruction (e.g. aortic or mitral valve stenosis, asymmetric septal hypertrophy, malfunctioning prosthetic valve).
3. Constrictive pericarditis.
4. Complex congenital heart disease.
5. Syncopal episodes of unknown etiology \< 3 months before informed consent.
6. Planned cardiac surgery or angioplasty within three months.
7. Uncontrolled hypertension on treatment (i.e.Blood pressure ( BP) \> 160/100).
8. Heart transplant recipient.
9. Strokes due to subarachnoid hemorrhage

C. Other conditions:

1. Significant renal disease defined as:

   1. Renal artery stenosis;
   2. Creatinine clearance \< 0.6 ml/min or serum creatinine \> 265 umol/L (\> 3.0 mg/dL);
   3. Hyperkalemia: potassium \> 5.5 mmol/L.
   4. Proteinuria\* (for TRANSCEND only).
2. Hepatic dysfunction as defined by the following laboratory parameters: Serum Glutamate Pyruvate Transaminase( SGPT) Alaninaminotransferase (ALT) or Serum Glutamic Oxaloacetic Transaminase (SGOT) Aspartate aminotransferase (AST) \> than 4 times upper limit of normal or additional criteria for hepatic impairment the upper limit of normal range, total Bilirubin \> 20 umol/L, biliary obstructive disorders.
3. Uncorrected volume depletion or sodium depletion.
4. Primary aldosteronism.
5. Hereditary fructose intolerance.
6. Any other major non-cardiac illness expected to reduce life expectancy or interfere with study participation.
7. Patient is simultaneously taking another experimental drug.
8. Patient with significant disability that precludes regular attendance at clinic for follow-up.
9. Patient has sufficient disability or other incapacity that precludes regular attendance at clinic for follow-up.
10. Unable or unwilling to provide written informed consent.
D: Inclusion Criteria:

* Informed consent
* Stable hypertension defined as no new antihypertensive medication started within 6 weeks of Visit 1
* Minimum 6-month history of hypertension and primary glomerular disease
* Hypertensive nephrosclerosis
* Diabetic nephropathy with stable proteinuria as defined by ≥ 1g/24 hours on more than one occasion within 6 months prior to Visit 1

Exclusion Criteria:

* Persistent hypertension
* New anti-hypertensive medications started within 6 weeks of Visit 1
* Significant cardiac disease or Liver disease
* Females of childbearing potential without reliable contraception
* Pregnant women and women who are breast-feeding

Answer: D