Please select the eligibility criteria that correspond to the clinical trial below.
Title: HOPE-2 Study (Heart Outcomes Prevention Evaluation-2 Study)
Brief Summary: The purpose of the HOPE-2 study is to determine whether long term supplementation with folic acid, vitamins B6 and B12 aimed at homocyst(e)ine reduction reduces the rates of major fatal and nonfatal cardiovascular events in patients with established cardiovascular disease and/or diabetes mellitus.


Options:
A: Inclusion Criteria:

* Women and men 55 years of age or over with established CVD and at high risk for future fatal and nonfatal CV events, defined as:

  1. Documented coronary artery disease (CAD);
  2. Documented peripheral vascular disease (PVD);
  3. Documented cerebrovascular disease;
  4. Diabetes with one of the following; additional cardiovascular risk factors:

  i) hypertension (BP \>160 mmHg systolic or \>90 mmHg diastolic or on treatment); ii) total cholesterol \>5.2 mmol/L (\>200 mg/dl); iii) HDL cholesterol \<0.9 mmol/L (3.5 mg/dl); iv) current cigarette smoker; v) any evidence of previous vascular disease
* Provision of informed consent

Exclusion Criteria:

* Current use of any vitamin supplements containing folic acid \>200 micrograms/day. The patients taking such vitamin supplements can be asked if they agree to discontinue these supplements. If they agree, they can be randomized to the study following a one month wash-out period.
* Known previous adverse reactions to folic acid and/or vitamin B6 and/or B12.
* Planned cardiac, peripheral or cerebrovascular revascularization, defined as a decision taken by the patient and his or her physician(s) to perform surgical or percutaneous transluminal revascularization within the next 6 months.
* Hemodynamically significant primary valvular outflow tract obstruction (e.g. mitral stenosis, asymmetric septal hypertrophy, malfunctioning prosthetic valve).
* Constrictive pericarditis.
* Complex congenital heart disease.
* Syncopal episodes presumed to be due to uncontrolled life-threatening arrhythmias (asymptomatic arrhythmias including ventricular tachycardia are not exclusion criteria.
* Uncontrolled hypertension.
* Cor pulmonale.
* Heart transplant recipient.
* Other important non-cardiovascular disease(s) expected to limit compliance and/or impact on patient's ability to complete the study, such as: \*history of alcohol or drug abuse, \*psychiatric disorders, \*senility, \*severe physical disability, \*illnesses including terminal stage of cancer and other major systemic illnesses expected to limit the patient's ability to comply with the study protocol and to complete the study.
B: Inclusion Criteria:

* Type 2 diabetes mellitus
* Patients are on treatment with angiotensin converting enzyme inhibitors (ACEi) and/or angiotensin II antagonists (AIIA) in an unchanged dose for at least 3 months
* Active diabetic nephropathy as indicated by presence of microalbuminuria (15-300 mg/24 h urine) in at least two samples within 2-6 weeks in advance of inclusion in the trial
* HbA1c \< 8.5%, a higher HbA1c \< 9.5% is acceptable if the treating physician and the patient have accepted that striving for lower values is an unreachable goal (patients with high HbA1c values are the ones that one would expect to be benefit most from treatment with benfotiamine)
* eGFR (estimated by MDRD formula) \> 30 ml/min
* Males and postmenopausal females
* Written informed consent

Exclusion Criteria:

* Renal impairment by other causes than diabetes
* Stage of the disease more severe than indicated in Inclusion criteria (macroalbuminuria or renal insufficiency)
* Severe hypoglycemia during the last 3 months, needing help from another person
* Severe hepatopathy (laboratory values about three times higher than normal
* Endocrine disorders, e.g. hyper/hypothyroidism
* Blood pressure \> 160/90 mmHg
* Severe cardiac function disturbances and severe heart rhythm disturbances
* Neoplasm's (excluding history of treated skin cancer of the type basal cell carcinoma BCC or squamous cell carcinoma SCC)
* Severe general diseases or mental disorders making the participation in the study impossible
* Drug abuse
* Female patients during pregnancy and lactation period and female patients with active menses during the past year
* Hypersensitivity to benfotiamine
* HbA1c \> 9.5%
* Use of thiamine containing supplements during the last 3 months
* Participation in another study within one month before joining the benfotiamine study
C: Inclusion Criteria:

1. A diagnosis of type 2 diabetes mellitus first made at age 30 years or older
2. Age 55 years or older at entry
3. Ability to provide informed consent
4. A substantially elevated risk of cardiovascular disease, indicated by:

   * A history of major macrovascular disease defined as any one of: stroke, myocardial infarction, hospital admission for transient ischaemic attack, hospital admission for unstable angina, coronary artery bypass graft, percutaneous transluminal coronary angioplasty (with or without stenting), peripheral revascularisation (angioplasty or surgery) or amputation secondary to vascular disease or
   * A history of major microvascular disease defined as any one of nephropathy (albumin:creatinine ratio \>300ug/mg), retinal photocoagulation therapy, proliferative retinopathy (new blood vessels on the disc or elsewhere, vitreous haemorrhage, pre-retinal haemorrhage, or fibrous proliferations on the disc or elsewhere), macular oedema (retinal thickening within one disc diameter of the macular centre) or blindness in either eye (corrected visual acuity 6/60 or worse, persisting for three months or more) not known to be due to non-diabetic causes or
   * A first diagnosis of type 2 diabetes made 10 or more years prior to entry or
   * Another major risk factor for vascular disease defined as any one of: current daily cigarette smoking, total cholesterol greater than 6.0 mmol/l (with or without cholesterol lowering treatment), HDL cholesterol \<1.0 mmol/l, microalbuminuria (albumin:creatinine ratio 30-300ug/mg) or
   * Age 65 years or over

Exclusion Criteria:

1. A definite contraindication to treatment with an ACE inhibitor or a thiazide-like diuretic
2. A specific indication for treatment with an ACE inhibitor other than perindopril 2-4 mg daily (see also section 5.2.3) or a thiazide-like diuretic
3. A definite and specific indication for treatment with gliclazide or a haemoglobin A1c control target of 6.5% or less
4. A definite contra-indication to treatment with gliclazide or a haemoglobin A1c control target of 6.5% or less
5. A definite indication for long-term full-dose or bed-time insulin therapy
6. Participation in a trial within the month prior to the Registration Visit or current participation in another trial

Other potential reasons for ineligibility include:

* High probability of non-adherence to study treatment or follow-up
* Current clinical instability (e.g. a major cerebral or coronary event or sight-threatening retinopathy or macular oedema within the previous few weeks)
* Life threatening non-vascular disease other than diabetes and its complications
* Moderate or severe dementia
* Major disability that is likely to prevent regular attendance at study clinics

Final decisions about eligibility were made at the discretion of the study investigator and the potential study participant, in the light of any requirements or guidance from local ethics committees and other regulatory bodies.
D: Inclusion Criteria:

* Age \> 18 years
* Capable of giving informed consent
* Duration of peritoneal dialysis \> 3 months
* Dose of phosphate binder(s) stable over previous 2 week period
* Plasma phosphours \> 4.9 mg/dL based on most recent laboratory data within 1 month of enrollment

Exclusion Criteria:

* Pregnancy
* Known liver disease
* Active peptic ulcer disease
* Treatment with carbamazepine
* Intolerance to niacinamide or niacin
* Current medication regimen including niacin or niacinamide \> 100 mg daily
* Planned or expected surgical procedure in the next 4 months
* Patients in nursing home or extended care facilities where administration of the study drug may not be appropriately given

Answer: A