Please select the eligibility criteria that correspond to the clinical trial below.
Title: CSP #465 - Glycemic Control and Complications in Diabetes Mellitus Type 2 (VADT)
Brief Summary: This study is a prospective, 2-arm, randomized controlled trial to determine whether glycemic control, achieved through intensification of treatment, is effective in preventing clinical macrovascular complications in patients with type 2 DM who are no longer responsive to oral agents alone. The study consists of a two-year accrual period and five years of follow-up (7 years total) of 1700 patients across 20 centers. We have powered the study to detect a 21% reduction in the primary event rate. Additional study goals are to determine whether the expenditures, discomfort, and adverse effects associated with intensive intervention are justified in terms of their clinical benefits, considering both macrovascular and microvascular complications.


Options:
A: Inclusion Criteria:

* Patients with type 2 DM who are no longer responsive to maximum dose of one or more oral agents.

Exclusion Criteria:

* Angina pectoris, Canadian Class I-II,
* congestive heart failure, Class III-IV,
* stroke, incapacitating or in last 6 months,
* Myocardial infarction (MI) or invasive cardiovascular procedure within the past six months,
* ongoing diabetic gangrene,
* BMI \> 40,
* hemoglobinopathy that interferes with A1c monitoring,
* serum creatinine \> 1.6 mg/dL,
* fasting C-peptide \< 0.21 pmol/ml,
* Alanine Amino Transaminase (ALT) \> 3 times normal or serum bilirubin \> 1.9 mg/dL,
* malignancy or noncardiac life-threatening diseases making life expectancy \< 5 years,
* autonomic neuropathy,
* symptomatic pancreatic insufficiency (endocrine or exocrine),
* recurrent seizures within the past year,
* hypopituitarism,
* pregnancy, lactation, or planning a pregnancy,
* active psychosis or substance abuse,
* lack of access to a person who can assist or be called in an emergency,
* underlying conditions that in the site PI's judgment may prevent adherence to protocol,
* current participation in another clinical trial
B: Inclusion Criteria:

Age \>= 18 years -Individuals \< 18 years old are not being included because proliferative diabetic retinopathy (PDR) is so rare in this age group that the diagnosis of PDR may be questionable.

Diagnosis of diabetes mellitus (type 1 or type 2)

Any one of the following will be considered to be sufficient evidence that diabetes is present:

* Current regular use of insulin for the treatment of diabetes
* Current regular use of oral anti-hyperglycemia agents for the treatment of diabetes
* Documented diabetes by American Diabetes Association (ADA) and/or World Health Organization (WHO) criteria (see Procedures Manual for definitions) Able and willing to provide informed consent.

Meets at least all of the following ocular criteria criteria:

* Presence of PDR which the investigator intends to manage with PRP alone but for which PRP can be deferred for at least 4 weeks in the setting of intravitreal ranibizumab, in the investigator's judgment.
* Best corrected Electronic-Early Treatment Diabetic Retinopathy Study (E-ETDRS) visual acuity letter score \> 24 (approximate Snellen equivalent 20/320) on the day of randomization.
* Media clarity, pupillary dilation, and study participant cooperation sufficient to administer PRP and obtain adequate fundus photographs and optical coherence tomography (OCT).

  * Investigator must verify accuracy of OCT scan by ensuring it is centered and of adequate quality

Exclusion Criteria:

Significant renal disease, defined as a history of chronic renal failure requiring dialysis or kidney transplant.

A condition that, in the opinion of the investigator, would preclude participation in the study (e.g., unstable medical status including blood pressure, cardiovascular disease, and glycemic control).

* Individuals in poor glycemic control who, within the last 4 months, initiated intensive insulin treatment (a pump or multiple daily injections) or plan to do so in the next 4 months should not be enrolled.

Participation in an investigational trial within 30 days of randomization that involved treatment with any drug that has not received regulatory approval for the indication being studied.

* Study participants cannot receive another investigational drug while participating in the study.

Known allergy to any component of the study drug.

Blood pressure \> 180/110 (systolic above 180 or diastolic above 110).

* If blood pressure is brought below 180/110 by anti-hypertensive treatment, individual can become eligible.

Myocardial infarction, other acute cardiac event requiring hospitalization, stroke, transient ischemic attack, or treatment for acute congestive heart failure within 4 months prior to randomization.

Systemic anti-VEGF or pro-VEGF treatment within 4 months prior to randomization.

* These drugs should not be used during the study.

For women of child-bearing potential: pregnant or lactating or intending to become pregnant within the next 3 years.

* Women who are potential study participants should be questioned about the potential for pregnancy. Investigator judgment is used to determine when a pregnancy test is needed.

Individual is expecting to move out of the area of the clinical center to an area not covered by another Diabetic Retinopathy Clinical Research Network (DRCR.net) certified clinical center during the 3 years of the study.

Individual has any of the following ocular characteristics:

* History of prior panretinal photocoagulation (prior PRP is defined as ≥ 100 burns outside of the posterior pole)
* Tractional retinal detachment involving the macula.

  -- A tractional retinal detachment is not an exclusion if it is outside of the posterior pole (not threatening the macula) and in the investigator's judgment, is not a contraindication to intravitreal ranibizumab treatment and also does not preclude deferring PRP for at least 4 weeks in the setting of intravitreal ranibizumab
* Exam evidence of neovascularization of the angle (neovascularization of the iris alone is not an exclusion if it does not preclude deferring PRP for at least 4 weeks in the investigator's judgment).
* If macular edema is present, it is considered to be primarily due to a cause other than diabetic macular edema.

  -- An eye should not be considered eligible if:
  * macular edema is present that is considered to be related to ocular surgery such as cataract extraction or
  * clinical exam and/or OCT suggest that vitreoretinal interface abnormalities disease (e.g., a taut posterior hyaloid or epiretinal membrane) is the primary cause of any macular edema.
* An ocular condition is present (other than diabetic retinopathy) that, in the opinion of the investigator, might alter visual acuity during the course of the study (e.g., retinal vein or artery occlusion, uveitis or other ocular inflammatory disease, neovascular glaucoma, etc.).

  -- A vitreous or preretinal hemorrhage is not an exclusion if it is out of the visual axis and in the investigator's judgment is not having any affect on visual acuity.
* Substantial cataract that, in the opinion of the investigator, is likely to be decreasing visual acuity by 3 lines or more (i.e., cataract would be reducing acuity to 20/40 or worse if eye were otherwise normal).
* History of intravitreal anti-VEGF treatment at any time in the past 2 months.
* History of corticosteroid treatment (intravitreal or peribulbar) at any time in the past 4 months.

  --If the investigator believes that there may still be a substantial effect 4 months after prior treatment (e.g., dose of intravitreal triamcinolone higher than 4 mg), the eye should not be included.
* History of major ocular surgery (including vitrectomy, cataract extraction, scleral buckle, any intraocular surgery, etc.) within prior 4 months or anticipated within the next 6 months following randomization.
* History of (yttrium-aluminum-garnet) YAG capsulotomy performed within 2 months prior to randomization.
* Aphakia.
* Uncontrolled glaucoma (in investigator's judgment).
* Exam evidence of severe external ocular infection, including conjunctivitis, chalazion, or substantial blepharitis
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:

* Participating in the ACCORD study

Exclusion Criteria:

* Has had laser photocoagulation for DR
* Has had vitrectomy surgery for DR

Answer: A