RCA for CRRT in Hyperlactatemia Patient With Increased Bleeding Risk

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

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.

Study Overview

• Status: Unknown
• Conditions: Bleeding; Continuous Renal Replacement Therapy; Hyperlactatemia
• Intervention / Treatment: Procedure: Regional citrate anticoagulation CRRT; Procedure: No-anticoagulation CRRT

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 Type: Interventional
• Enrollment (Anticipated): 80
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Ming Bai, MD; Phone Number: +86029-84775197; Email: mingbai1983@126.com

Study Locations

• China
  • Shaanxi
    • Xi'an, Shaanxi, China, 710032
      • Xijing Hospital of Nephrology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Reginal citrate anticoagulation; 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; 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.
Active Comparator: No-anticoagulation; 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; Patients accepted no-anticoagulation CRRT. Blood flow 200 ml/h. The replacement fluid was infused 50% predilution and 50% post-dilution.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Air Force Military Medical University, China
• Investigators: Principal Investigator: Shiren Sun, MD, Xijing Hospital

Study record dates

Study Major Dates

• Study Start (Anticipated): March 30, 2020
• Primary Completion (Anticipated): March 1, 2022
• Study Completion (Anticipated): March 3, 2022

Study Registration Dates

• First Submitted: February 29, 2020
• First Submitted That Met QC Criteria: March 18, 2020
• First Posted (Actual): March 19, 2020

Study Record Updates

• Last Update Posted (Actual): March 19, 2020
• Last Update Submitted That Met QC Criteria: March 18, 2020
• Last Verified: March 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Metabolic Diseases; Hemorrhage; Hyperlactatemia
• Other Study ID Numbers: RCA-CRRT-Hyperlactatemia

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No