RCA for CRRT in Hyperlactatemia Patient With Increased Bleeding Risk

Not Applicable

• Conditions: Continuous Renal Replacement Therapy; Bleeding; Hyperlactatemia
• Interventions: Procedure: No-anticoagulation CRRT; Procedure: Regional citrate anticoagulation CRRT

• Registration Number: NCT04315623
• Lead Sponsor: Air Force Military Medical University, China

Brief Summary

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

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.

Study Timeline

• Study First Submitted: 2020-02-29
• Status Verified: 2020-03
• Study First Submitted QC: 2020-03-18
• Last Update Submitted: 2020-03-18
• Study First Posted: 2020-03-19
• Last Update Posted: 2020-03-19
• Study Start: 2020-03-30
• Primary Completion: 2022-03-01
• Study Completion: 2022-03-03

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 80

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
No-anticoagulation	No-anticoagulation CRRT	Patients accepted no-anticoagulation CRRT. Blood flow 200 ml/h. The replacement fluid was infused 50% predilution and 50% post-dilution.
Reginal citrate anticoagulation	Regional citrate anticoagulation CRRT	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.

Primary Outcome Measures

Name	Time	Method
Filter failure	72 hours	TMP (transmembrane pressure) ≥ 300 mmHg, extracorporeal coagulation due to blood clots

Secondary Outcome Measures

Name	Time	Method
Hypocalcemia	72 hours	Ionized Ca2+ \< 1.0
Alkalosis	72 hours	Blood pH \> 7.45
Serum Total Ca2+/ion Ca2+ level	2, 6, 12, 20, 28, 36, 44, 52, 60, and 72 hours	Serum Total Ca2+/ion Ca2+ level
Acidosis	72 hours	Blood pH \< 7.35
Serum AST level	Every 24 hours up to 72 hours	AST
Serum citrate concentration	2, 6, 12, 20, 28, 36, 44, 52, 60, and 72 hours	Citrate concentration
citrate accumulation	72 hours	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.
Serum total bilirubin level	Every 24 hours up to 72 hours	Total bilirubin
Serum lactate level	2, 6, 12, 20, 28, 36, 44, 52, 60, and 72 hours	Serum lactate level
APTT	Every 24 hours up to 72 hours	activated partial thromboplastin time
PT	Every 24 hours up to 72 hours	Prothrombin time
Bleeding	72 hours	Bleeding episode during the CRRT
INR	Every 24 hours up to 72 hours	International normalized ratio
Mortality	Up to 3 months	In-hospital mortality

Trial Locations

Locations (1)

Xijing Hospital of Nephrology; 🇨🇳 Xi'an, Shaanxi, China