Please select the eligibility criteria that correspond to the clinical trial below.
Title: Comparison of Efficacy of Losartan/Spironolactone and Losartan/Enalapril on Urinary Albumin Excretion, Estimated Glomerular Filtration Rate, and Blood Pressure in Patients With Type 2 Diabetes Nephropathy
Brief Summary: The detrimental effects of aldostrone are not adequately arrested by the use of angiotensin converting enzyme (ACE), angiotensin II receptor blocker (ARB) or a combination of both. Recent evidence has provided robust evidence that aldostrone escape plays an important role in this regard. It is believed that aldostrone escape occurs quite commonly with reports indicating prevalence rates as high as 22% with ARBs and 40% with ACE inhibitors. In a trial of patients with diabetes and hypertension it was shown that treatment of aldostrone escape with spironolactone 25 mg daily for three months significantly reduces proteinuria. A number of other trials have similarly observed that addition of spironolactone to an ACE inhibitor based regimen provides additional benefits on proteinuria reduction, blood pressure control, and prevention of glomerular filtration rate (GFR) decline. Most of the available trials in this regard are of short duration (e.g. three months), and have added spironolactone to an ACE or ACE+ARB based regimen (the so-called triple blockade). Currently, evidence evaluating efficacy of a combined ARB+spironolactone regimen compared with conventional double RAS blockade (i.e. ACE+ARB) is lacking. Hence, this randomized open label trial was initiated to determine the effects of addition of spironolactone 25 mg daily to losartan over a period of 18 months.


Options:
A: Inclusion Criteria:

* Male or female age \>= 60 years with current symptoms of heart failure consistent with New York Heart Association (NYHA) class II-IV
* Left ventricular ejection fraction (LVEF) \> = 45%
* Willing to provide written informed consent AND hospitalization for heart failure within the past 6 months OR various abnormalities in electrocardiogram, echocardiogram or chest x-ray indicating heart disease.

Exclusion Criteria:

* Acute myocardial infarction within 3 months;
* Heart revascularization procedure within 3 months;
* Hospitalization for angina within 3 months;
* Other heart surgery
* Life-threatening or uncontrolled arrhythmia
* Subjects with an implantable cardioverter-defibrillator that has discharged in the past 3 months;
* Stroke or surgery of the arteries in the brain within 3 months;
* Serious lung disease which requires use of home oxygen.
* Significantly low blood pressure
* Significantly high blood pressure
* Other known diseases that may limit life expectancy to \<3 years;
* Known or suspected bilateral kidney artery narrowing;
* Geographic or social factors making study participation and follow-up impractical.
B: Inclusion Criteria:

* type 2 diabetes patients with diabetic nephropathy in the range of micro- or macroalbuminuria
* treatment with combination of enalapril and losartan for more than one year

Exclusion Criteria:

* history of non-adherence to prescribed medication assessed by the prescribing physician
* baseline potassium \> 5.5 meq/L
* chronic kidney disease stages 4 or 5
* history or evidence of non-diabetic kidney disease
C: Inclusion Criteria:

* Mild-moderate chronic kidney disease (glomerular filtration rate \[GFR\] 40-80 mls/min calculated by Cockroft-Gault equation)
* Controlled blood pressure (\< 130/80 mmHg)
* On established (\> 6 weeks) treatment with angiotensin converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs).

Exclusion Criteria:

* Diabetes mellitus
* Clinical evidence of fluid overload or hypovolaemia
* Recent (\< 2 months) acute myocardial infarction
* Left ventricular (LV) dysfunction (ejection fraction \< 40% by echocardiography).
D: Inclusion Criteria:

* Men aged 18 years and older or postmenopausal women aged 55 years and older or women aged 18 years and older without childbearing potential based on surgical treatment such as bilateral tubal ligation, bilateral ovarectomy, or hysterectomy
* Clinical diagnosis of CHF (chronic heart failure), either ischemic or non-ischemic, NYHA (New York Heart Association) class II - III, treated with evidenced-based therapy for CHF, e.g. beta-blockers and ACE (angiotensin-converting enzyme) inhibitors or ARB (angiotensin receptor blocker) as well as diuretics, unless contraindicated or not tolerated
* Known kidney damage for \>/= 3 months, as defined by structural or functional abnormalities of the kidney, and

  * Part A: 60 mL/min/1.73 m\*2 \</= eGFR (estimated Glomerular Filtration Rate) \< 90 mL/min/1.73 m\*2 (MDRD, Modification of Diet in Renal Disease) at the screening visit
  * Part B: 30 mL/min/1.73 m\*2 \</= eGFR \<= 60 mL/min/1.73 m\*2 (MDRD) at the screening visit
* Serum potassium \</= 4.8 mmol/L at the screening visit
* Systolic blood pressure \>/= 90 mmHg without signs or symptoms of hypotension at the screening visit

Exclusion Criteria:

* Known hypersensitivity to the study drug (active substance or excipients) or spironolactone and respective excipients (Part B only)
* Subjects with anuria, acute renal failure, or Addison's disease
* Acute coronary syndrome or unstable coronary artery disease within 30 days prior to randomization
* Valvular heart disease requiring surgical intervention during the course of the study
* History of hospitalization for hyperkalemia or acute renal failure induced by previous aldosterone antagonist treatment

Answer: B