Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Randomized, Double-Blind, Placebo Controlled, Parallel Group Study of Patiromer for the Enablement of Spironolactone Use for Blood Pressure Control in Patients With Resistant Hypertension and Chronic Kidney Disease
Brief Summary: The purpose of this study is to determine if patiromer treatment in chronic kidney disease (CKD) subjects receiving spironolactone for the treatment of resistant hypertension will result in more persistent use of spironolactone through prevention of hyperkalemia and lead to improved blood pressure control compared with treatment with spironolactone alone (placebo).


Options:
A: INCLUSION CRITERIA:

* Heart failure as defined by at least one of symptom (paroxysmal nocturnal dyspnea; orthopnea; or dyspnea on mild or moderate exertion) at the time of screening and at least one sign (any rales post cough; jugular venous pressure(JVP) greater than or equal to 10cm of water(H2O); lower extremity edema; or chest x-ray demonstrating pleural effusion, pulmonary congestion, or cardiomegaly) within 12 months prior to study entry:
* left ventricular ejection fraction greater than or equal to 45% (per local reading); the ejection fraction must have been obtained within 6 months prior to randomization and after any MI or other event that would affect ejection fraction
* Controlled systolic blood pressure(BP), defined as a target systolic BP less than 140 mm Hg; participants with BP up to and including 160 mm Hg are eligible for enrollment if they are on three or more medications to control BP
* Serum potassium less than 5.0 mmol/L prior to randomization
* At least one hospital admission for which heart failure was a major component of the hospitalization some time within the 12 months prior to study entry OR brain natriuretic peptide (BNP) greater than or equal to 100pg/ml or N-terminal pro-BNP greater than or equal to 360pg/ml within the 60 days prior to study entry
* Women of child-bearing potential must have a negative serum/urine pregnancy test within 72 hours prior to randomization, must not be lactating, and must agree to use an effective method of contraception during the entire course of study participation
* Willing to comply with scheduled visits
* Informed consent form signed by the subject prior to participation in the trial

EXCLUSION CRITERIA:

* Severe systemic illness with an expected life expectancy of less than 3 years
* Chronic pulmonary disease requiring home O2, oral steroid therapy, or hospitalization for exacerbation within 12 months of study entry, or significant chronic pulmonary disease in the opinion of the investigator
* Known infiltrative or hypertrophic obstructive cardiomyopathy or known pericardial constriction
* Primary hemodynamically significant uncorrected valvular heart disease, obstructive or regurgitant, or any valvular disease expected to lead to surgery during the trial
* Atrial fibrillation with a resting heart rate greater than 90 bpm
* MI in the past 90 days
* Coronary artery bypass graft surgery in the past 90 days
* Percutaneous coronary intervention in the past 30 days
* Heart transplant recipient
* Currently implanted left ventricular assist device
* Stroke in past 90 days
* Systolic BP (SBP) greater than 160 mm Hg
* Known orthostatic hypotension
* Gastrointestinal disorder that could interfere with study drug absorption
* Use of any aldosterone antagonist or potassium sparing medication in the last 14 days or any known condition that would require the use of an aldosterone antagonist during study participation;
* Known intolerance to aldosterone antagonists
* Current lithium use
* Current participation (including prior 30 days) in any other therapeutic trial
* Any condition that, in the opinion of the investigator, may prevent the participant from adhering to the trial protocol
* History of hyperkalemia (serum potassium greater than or equal to 5.5mmol/L) in the past 6 months or serum potassium greater than or equal to 5.0mmol/L within the past 2 weeks
* Severe renal dysfunction, defined as an estimated glomerular filtration rate(GFR) less than 30ml/min. Participants with serum creatinine greater than or equal to 2.5mg/dl are also excluded even if their GFR is greater than or equal to 30ml/min
* Known chronic hepatic disease, defined as aspartate aminotransferase(AST) and alanine aminotransferase(ALT) levels greater than 3.0 times the upper limit of normal as read at the local lab.
B: Inclusion Criteria:

* Age ≥ 18 years
* Taking at least three medications for blood pressure (one a diuretic)
* Uncontrolled high blood pressure
* Abnormal kidney function (with-eGFR, a measure of kidney function, of 25 - ≤ 45 mL/min/1.73m2
* Normal Blood serum Potassium in a specific range (4.3 - 5.1 mEq/L)

Exclusion Criteria:

* History of untreated known causes of high blood pressure, excluding kidney disease (not CKD)
* Inability to measure BP
* Not taking high blood pressure medications as prescribed medications
* Recent change in renal function (in the past 3 months) which has required hospitalization or dialysis
* Renal transplant
* History of cancer within past 12 months
* Recent cardiovascular event with last 3 months
* Clinically significant abnormalities of heart rhythm (ventricular arrhythmia or atrial fibrillation with uncontrolled heart rate)
* Inability to take study medication
* Alcoholism
C: Inclusion Criteria:

* Proteinuria \> 500 mg/24 hours
* Hypertension or anti-hypertensive treatment

Exclusion Criteria:

* Diabetic nephropathy
* GFR\< 20 ml/min
* P-potassium between 3,5 mmol/l and 5,0 mmol/l
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