Please select the eligibility criteria that correspond to the clinical trial below.
Title: Safety and Efficacy of the Use of Regional Anticoagulation With Citrate in Continuous Venovenous Hemofiltration, a Randomized Controlled Trial Comparing Anticoagulation With Citrate to the Low Molecular Weight Heparin Nadroparin
Brief Summary: Severely ill patients admitted to the intensive care unit may develop an acute failure of kidney function. To bridge the period to recovery, renal function is temporarily replaced by continuous venovenous hemofiltration (CVVH). To prevent clotting of the hemofiltration circuit, heparin is generally used, providing anticoagulation in the circuit and the patient. As a result, bleeding complications may occur, necessitating the transfusion of blood. Anticoagulation of the circuit can also be obtained with the use of tri-sodium citrate, which provides anticoagulation of the circuit without affecting coagulation in the patient and thus without increasing his/her risk of bleeding. The use of citrate may however cause metabolic complications.

Primary aim of the present study is to show in a larger group of intensive care patients whether the use of regional anticoagulation with citrate is safe compared to systemic anticoagulation with the low molecular weight heparin nadroparin.


Options:
A: Inclusion Criteria:

1. Patient must be receiving medical care in an intensive care unit (ICU) (e.g., medical ICU, surgical ICU, cardiothoracic ICU, Trauma ICU, Mixed ICU, other).
2. Adult patients with AKI or other serious conditions who require treatment with CRRT.
3. Patients are expected to remain in the ICU and on CRRT for at least 72 hours after randomization.
4. Patients already receiving standard-of-care CRRT must be randomized within 24 hours of initiation of their standard-of-care CRRT.

Exclusion Criteria:

1. Patients requiring systemic anticoagulation with antithrombotic agents for reasons other than CRRT. The exception is patients receiving subcutaneous heparin for deep vein thrombosis prophylaxis according to institutional practice or patients on aspirin may be enrolled.
2. Patients in whom citrate anticoagulation is contraindicated such as patients with a known allergy to citrate or who have experienced adverse events associated with citrate products including patients with a prior history of citrate toxicity or patients with uncorrected severe hypocalcemia (whether in the context of current citrate administration or due to the underlying disease state).
3. Patients who are not candidates for CRRT.
4. Patients who are receiving extracorporeal membrane oxygenation (ECMO) therapy.
5. Patients with severe coagulopathy \[i.e., platelets \< 30,000/mm3, international normalized ratio (INR) \> 2, partial thromboplastin time (PTT) \> 50 seconds\] including severe thrombocytopenia (platelets \< 30,000/mm3), HIT (heparin induced thrombocytopenia), ITP (idiopathic thrombocytopenia purpura), and TTP (thrombotic thrombocytopenia purpura) should not be enrolled in the trial.
6. Patients with fulminant acute liver failure or acute on chronic liver failure as documented by a Child-Pugh Liver Failure Score \> 10.
7. Patients with refractory shock associated persistent, worsening with lactic acidosis (lactate \> 4 mmol/L). However, patients with improving subsequent serum lactate levels may be enrolled.
8. Patients unlikely to survive at least 72 hours.
9. Female patients who are pregnant, lactating, or planning to become pregnant during the study period.
10. Patients who are currently participating in another interventional clinical study.
11. Patients with a medical condition that may interfere with the study objectives.
B: Inclusion Criteria:

1. The treating clinician believes that the patient requires CRRT for acute renal failure.
2. The clinician is uncertain about the balance of benefits and risks likely to be conferred by treatment with higher intensity or lower intensity CRRT.
3. The treating clinicians anticipate treating the patient with CRRT for at least 72 hours.
4. Informed consent has been obtained
5. The patient fulfils ONE of the following clinical criteria for initiating CRRT:

   * Oliguria (urine output \< 100ml/6hr) that has been unresponsive to fluid resuscitation measures.
   * Hyperkalemia (\[K+\] \> 6.5 mmol/L).
   * Severe acidemia (pH \< 7.2).
   * Urea \> 25 mmol/liter.
   * Creatinine \>300 micromol/L in the setting of ARF.
   * Clinically significant organ oedema in the setting of ARF (eg: lung).

Exclusion Criteria:

1. Patient age is \<18 years.
2. Death is imminent (\<24 hours).
3. There is a strong likelihood that the study treatment would not be continued in accordance with the study protocol.
4. The patient has been treated with CRRT or other dialysis previously during the same hospital admission.
5. The patient was on maintenance dialysis prior to the current hospitalisation.
6. The patient's body weight is \<60 kg or \>100kg.
7. Any other major illness that, in the investigator's judgment, will substantially increase the risk associated with the subject's participation in this study.
C: Inclusion Criteria:

* Age greater than 18 years
* Renal failure, electrolyte disturbance, or volume overload requiring continuous venovenous hemodialysis (CVVHD) as determined by the Nephrology consult service

Exclusion Criteria:

* Age less than 18 years
* Active bleeding
* Coagulopathy as defined by baseline INR \> 1.8, aPTT \> 45 seconds, or platelet count \< 50 thousand/μL
* Active administration of systemic anticoagulation (such as warfarin, therapeutic unfractionated heparin, or therapeutic enoxaparin)
* Contraindication to heparin (allergy, thrombocytopenia with platelet count \< 50, known or suspected heparin induced thrombocytopenia \[HIT\])
* Contraindication to systemic anticoagulation (recent surgical or other invasive procedure, significant bleeding disorder, concern for intracranial bleeding, or other contraindication as determined by treating physician)
* Administration of drotrecogin (Xigris™)
* Anticipated surgical or other invasive procedure that would necessitate withdrawal of anticoagulation within 72 hours
* Expected termination of continuous renal replacement therapy (CRRT) or death in \< 24 hours
* The need for more than 500 cc an hour of IV fluids delivered proximal to the filter for the purpose of performing continuous venovenous hemofiltration (CVVH) or continuous venovenous hemodiafiltration (CVVHDF)
D: Inclusion Criteria:

* Intensive care patients scheduled for continuous venovenous hemofiltration

Exclusion Criteria:

* Severe pre-existent liver failure (cirrhosis Child C), acute liver dysfunction as occurring with septic shock is not a reason for exclusion
* Active bleeding or bleeding necessitating the infusion of two red blood cell units within 24 hours before starting hemofiltration or a fall in hemoglobin of \> 0.5 mmol/l. A fall in hemoglobin/hematocrit as a result of fluid loading is not regarded as bleeding.
* Surgery within 24 h prior to CVVH.
* Patients needing full systemic anticoagulation (unfractionated heparin in a dose of \> 10000 IU/day, or nadroparin \> 3800 IU/day) for other reasons
* Expectation to die within 24 hours
* Chronic dialysis
* Proven or suspected heparin-induced thrombocytopenia

Answer: D