RCA for CRRT in Hyperlactatemia Patient With Increased Bleeding Risk

Study Overview
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Brief Summary
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The purpose of this single center, randomized, control, open-labeled study is to evaluate the effect and safety of RCA versus no anticoagulation for CRRT in hyperlactatemia patients with increased bleeding risk.

Detailed Description
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For continuous renal replacement therapy (CRRT) patients with shock and muscle hypoperfusion, which characterised by tissue hypoxia and hyperlactatemia, the Kidney Disease Improving Global Outcomes (KIDIGO) guideline recommended no use of regional citrate anticoagulation (RCA) considering the potential increased citrate accumulation (CA) risk. In the condition of increased bleeding, no-anticoagulation was recommended for these patients. However, CRRT processed without anticoagulation was proved to be associated with shorter filter lifespan. Therefore, the purpose of this single center, randomized, control, open-labeled study is to evaluate the safety and efficacy of RCA versus no-anticoagulation for CRRT in hyperlactatemia patients with increased bleeding risk.

Official Title
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Regional Citrate Anticoagulation Versus No-anticoagulation for CRRT in Hyperlactatemia Patients With Increased Bleeding Risk: a Randomized, Control, Open-labeled Clinical Trial

Conditions
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Continuous Renal Replacement Therapy, Hyperlactatemia, Bleeding

Intervention / Treatment
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* Procedure: Regional citrate anticoagulation CRRT
* Procedure: No-anticoagulation CRRT


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age≥16 years Hyperlactatemia (Lactic acid or serum lactate level > 2 mmol/L) Required CRRT Increased bleeding risk: PLT < 40 x 109, aPTT > 60 s, INR > 1.5, bleeding or active bleeding within 7 days, recent trauma or surgery (especially head trauma and neurosurgery), recent stroke, intracranial venous malformation or aneurysm, retinal hemorrhage, uncontrolled hypertension, and epidural catheter implantation. Exclusion Criteria: Drugs (biguanide, linezolid, cyanide, etc.) and congenital metabolic disorders (glucose-6 phosphatase and 1,6 phosphofructosase deficiency) and mitochondrial damage caused hyperlactatemia. Receiving systemic anticoagulant treatment (heparin/lmol/warfarin/aspirin, etc.) within 24 hours. Critical patients with lactic acid ≥15mmol\L (with a mortality of 100%) were excluded Patients with APTT > 100S were excluded (retrospective data suggested that this type of patients received CRRT treatment should last for more than 24 hours) Patients who are pregnant or during lactation Severe liver failure: child-pugh score >10 (chronic severe liver failure), MELD score > 30 (acute severe liver failure), total bilirubin >51 mol/L Patients with internal fistula were treated with CRRT Unable to cooperate with treatment due to mental problems (such as depression and mental illness) CRRT with arteriovenous fistula, or the prescribed treatment time < 12 hours

Ages Eligible for Study
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Minimum Age: 16 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Reginal citrate anticoagulation<br>Patients accepted regional citrate anticoagulation for CRRT. Blood flow 120-220 ml/h. Sodium citrate (4%) infusion before the filter in order to maintain post-filter ionCa2+ level between 0.25 to 0.35 mmol/L. Calcium gluconate supplementary after the filter to maintain serum ionCa2+ level between 1.0 to 1.2 mmol/L. Adjusting the infusion rate of sodium citrate and blood flow according to pre- and post-filtration ionCa2+. Adjusting the infusion rate of calcium gluconate according to the serum ionCa2+ level. | Procedure: Regional citrate anticoagulation CRRT<br>* Regional citrate anticoagulation Sodium citrate (4%) infusion before the filter in order to maintain post-filter ionCa2+ level between 0.25 to 0.35 mmol/L. Calcium gluconate supplementary after the filter to maintain serum ionCa2+ level between 1.0 to 1.2 mmol/L.<br>|
| Active Comparator: No-anticoagulation<br>Patients accepted no-anticoagulation CRRT. Blood flow 200 ml/h. The replacement fluid was infused 50% predilution and 50% post-dilution. | Procedure: No-anticoagulation CRRT<br>* Patients accepted no-anticoagulation CRRT. Blood flow 200 ml/h. The replacement fluid was infused 50% predilution and 50% post-dilution.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Filter failure | TMP (transmembrane pressure) ≥ 300 mmHg, extracorporeal coagulation due to blood clots | 72 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Serum Total Ca2+/ion Ca2+ level | Serum Total Ca2+/ion Ca2+ level | 2, 6, 12, 20, 28, 36, 44, 52, 60, and 72 hours | 
| Serum AST level | AST | Every 24 hours up to 72 hours | 
| Serum total bilirubin level | Total bilirubin | Every 24 hours up to 72 hours | 
| Serum citrate concentration | Citrate concentration | 2, 6, 12, 20, 28, 36, 44, 52, 60, and 72 hours | 
| Serum lactate level | Serum lactate level | 2, 6, 12, 20, 28, 36, 44, 52, 60, and 72 hours | 
| citrate accumulation | Metabolic acidosis with an increased anion gap, decreasing ionized calcium, elevated total calcium and the calcium ratio (totCa/ionCa) > 2.5 were considered as citrate accumulation. | 72 hours | 
| Hypocalcemia | Ionized Ca2+ < 1.0 | 72 hours | 
| Acidosis | Blood pH < 7.35 | 72 hours | 
| Alkalosis | Blood pH > 7.45 | 72 hours | 
| Bleeding | Bleeding episode during the CRRT | 72 hours | 
| APTT | activated partial thromboplastin time | Every 24 hours up to 72 hours | 
| PT | Prothrombin time | Every 24 hours up to 72 hours | 
| INR | International normalized ratio | Every 24 hours up to 72 hours | 
| Mortality | In-hospital mortality | Up to 3 months |