Please select the eligibility criteria that correspond to the clinical trial below.
Title: Effects of Tinzaparin Sodium on Cardio-vascular OUtcomes and on Blood Lipids in Diabetic Patients on Chronic HEmodialysis: A Long-term, Prospective Study (The "Tinzaparin COULD HELP" Study).
Brief Summary: Low molecular weight heparin (LMWH) provides a safe and effective alternative to UFH for hemodialysis anticoagulation. While unfractionated (UF) heparin has been implicated in hyper-lipidemia, the effect of LMWHs on the lipid profile in non-diabetic patients on chronic hemodialysis remains controversial. The effect of LMWH in diabetic patients, a high risk group for developing hyper-lipidemia and cardio-vascular disease, has not been studied.

The study intends to examine the long-term effects of the replacement of UFH by LMWH (tinzaparin sodium) on cardio-vascular outcomes and on lipoprotein profiles in a large group of diabetic patients stable on HD.


Options:
A: Inclusion Criteria:

* willingness to give written informed consent for participation in the study
* age 18-80 years old
* ability to understand and follow instructions and able to participate in the study for the entire period
* clinically stable (based on the investigator's judgment) within the three months prior to the screening visit
* written and signed agreement

Exclusion Criteria:

* antecedents of cerebrovascular accident, documented myocardial infarction, coronary angioplasty or bypass surgery within 6 months prior to the screening visit
* currently enrollment in any other investigational device or drug study, or participation in another clinical study within 30 days prior to the screening visit
* known or suspected drug or alcohol abuse
* known congenital or acquired bleeding disorders including hepatic failure and amyloidosis, present active major bleeding;
* increased risk of hemorrhage, due to: pericarditis or bacterial endocarditis, severe uncontrolled hypertension, active ulcerative and angiodysplastic gastrointestinal disease, hemorrhagic stroke, shortly after brain, spinal or ophthalmological surgery, concomitant treatment with platelet inhibitors, recent surgical procedures (especially with hemorrhagic complications or those in which hemorrhagic complications would be very severe - cardio-vascular, ophthalmological or neurological), planned surgical procedure within the next week, (history of) heparin-induced thrombocytopenia, with any other disease which, in the opinion of the investigator, makes unacceptable his/her inclusion in the study (known hypersensitivity to heparin, benzyl alcohol, or pork products that should not be treated with innohep®, severe psychiatric disorders, age \<18 years, malignant disorders and a life expectancy \<6 months, patients that were involved in another research study (studies) in the last month.
B: Inclusion Criteria:

1. hemodialysis patients with age \> 18 years on regular bicarbonate hemodialysis or hemodiafiltration treatment three times a week;
2. clinical stability at least three months before the study started;

Exclusion Criteria:

1. active gastrointestinal bleeding (one ore more positive hemoccult test in the last 8 weeks, melena or proctoraggia in the last 6 months )
2. hemorrhagic stroke
3. Myeloproliferative disorders
4. Hereditary deficiency of coagulation factors, LAC phenomenon or antiphospholipid syndrome
5. Malignant disease
6. Patient submitted to antithrombotic prophylaxis with LMWH
7. Immunosuppressive therapy
8. Participation in other clinical trials
C: Inclusion Criteria:

1. Signed Written Informed Consent
2. 18 years of age or older
3. Ongoing treatment with any chronic dialysis treatment OR an estimated glomerular filtration rate (eGFR)\* \<20 ml/min/1.73 m2 at least twice 3 months apart of which at least one occasion is \<15 ml/min/1.73 m2 due to CKD during the last year (12 months).
4. Diagnosis of chronic (i.e., repeated) paroxysmal, persistent, or permanent atrial fibrillation (AF) or atrial flutter (AFL)
5. CHA2DS2-VASc score ≥2 or more for men ≥3 or more for women as an indication for oral anticoagulation
6. Women of childbearing potential (WOCBP) should have a negative highly effective pregnancy test at screening and must agree to follow instructions for method(s) of contraception for the duration of treatment

Exclusion Criteria:

Participants may not be included in the study if any of the following criteria are met:

1. AF or AFL due to reversible causes (e.g., thyrotoxicosis, pericarditis)
2. Any degree of rheumatic mitral stenosis or moderate-to-severe non-rheumatic mitral stenosis at the time of inclusion into the study
3. Any condition other than AF or AFL that requires chronic anticoagulation (e.g., a prosthetic mechanical heart valve, antiphospholipid syndrome).
4. Any contraindication for anticoagulation including

   1. endocarditis
   2. documented intolerance for apixaban
   3. liver disease with documented coagulation disorder
   4. pregnancy or breast feeding
5. Active bleeding or serious bleeding within 3 months, or

   1. documented hemorrhagic blood dyscrasia
   2. patients currently receiving dual antiplatelet therapy
6. Planned for surgery

   1. kidney transplantation with a living donor within 3 months
   2. active on the kidney transplant waiting list at a kidney transplant center where apixaban use is prohibited
   3. valvular heart disease surgery
7. Current use of strong inhibitors of both CYP3A4 and P-glycoprotein in accordance with the summary of product characteristics (SmPC) of apixaban or regular intake of non-steroidal anti-inflammatory drugs (NSAID) or cyclooxygenase-2 (COX2) inhibitors
8. Any condition or circumstance in which the patient should not participate in the study according to the study investigator (reason documented in the pre-screening protocol)

Being active on the kidney transplant waiting list is not an exclusion criterion if it is allowed according to the current clinical guidelines at the transplant clinic where the patient is registered. The patient must report changes in waiting list status to the investigator promptly.
D: Inclusion Criteria:

* Prevalent NHHD patients who have received \>1 year dialysis with unfractionated heparin as anticoagulant
* Age \>= 18
* Informed consent available

Exclusion Criteria:

* History of intolerance to LMWHs during HD
* Receiving warfarin or other oral anticoagulant
* Pregnant patients

Answer: A