The Effect of Increasing Post-Filter Ionized Target on the Efficacy of Regional Citrate Anticoagulation During Continuous Renal Replacement Therapy in Intensive Care: a Multicenter Randomized Controlled Non-Inferiority Trial

APHP220257

Regional citrate anticoagulation (RCA) is the recommended method for anticoagulation in continuous renal replacement therapy (CRRT). However, the optimal post-filter ionized calcium (iCa) target level remains unclear. Currently, it is titrated to a post-filter iCa target ranging from 0.25 to 0.35 mmol/L, which is derived from a few underpowered trials. There are potential side effects associated with citrate administration, which may be increased in patient with liver failure and/or tissue dysoxia, such as alkalemia, acidemia, hypernatremia, hypocalcemia, hypomagnesemia, and citrate accumulation. Consequently, citrate anticoagulation is contraindicated in the most severe cases. The challenge is to use the minimum necessary dose of citrate to ensure both effective anticoagulation of the circuit and limit citrate administration to reduce the risks of metabolic complications and accumulation. This approach expands the indications for citrate, standardizes practice, and reduces financial costs. Investigators hypothesized that increasing the post-filter iCa target in RCA can limit the dose of citrate, thereby avoiding adverse effects (safety) without compromising the effectiveness of the treatment in preventing filter clotting. The aim of this study is to evaluate the impact of an increased post-filter iCa target from 0.25-0.35 to 0.35-0.45 mmol/L on the incidence of filter clotting for RCA-CRRT in critically ill patients. Investigators are designing a multicenter randomized controlled non-inferiority study.

2023-07-01

2025-01-01

2025-02-02

Recruiting

Early phase I

412

Inclusion Criteria: 1. Age ≥ 18 years old 2. Hospitalized in intensive care and presenting an indication for extra renal replacement therapy with Regional citrate anticoagulation (RCA) 3. Patients covered by social security regimen (excepting AME) 4. Having given their written consent or, if the patient is unable to consent and is accompanied, written consent from or legal representative or the close relative. If the patient is unable to consent and is not accompanied, due to the urgency of the procedure, the patient can also be included on the decision of the investigator (inclusion procedure in an emergency situation with subsequent necessity to sign a consent to prosecute). Exclusion Criteria: 1. Patients receiving curative systemic anticoagulation 2. Patients with a contraindication to the use of citrate : - Hypersensitivity to Regiocit® 3. Patients with a contraindication to the administration of the ancillary drugs Phoxilium® and calcium chloride 4. Patients with an absolute contraindication to the use of citrate due to a lack of metabolism in the Krebs cycle and therefore a major risk of accumulation: * Severe impairment of liver function with PT \< 30% and lactates \> 3mmol/l * Severe tissue dysoxia in uncontrolled shock with lactic acidosis (lactates \> 4mmol/l) * Drug toxicity (metformin, paracetamol, propofol, cyclosporine) 5. Pregnant woman 6. People under legal protection measure (guardianship or safeguard measures) 7. A patient legal representative or the close relative who declined to participate 8. Patient deprived of liberty by a judicial or administrative decision 9. Patient participating to another interventional study that may have an impact on the evaluation criteria of this study -

{'studyType': 'INTERVENTIONAL', 'phases': ['PHASE3'], 'designInfo': {'allocation': 'RANDOMIZED', 'interventionModel': 'PARALLEL', 'primaryPurpose': 'TREATMENT', 'maskingInfo': {'masking': 'NONE'}}, 'enrollmentInfo': {'count': 412, 'type': 'ESTIMATED'}}

2023-07-25