Citrate-based Regional Anticoagulation Versus Heparin for Continuous Renal Replacement Therapy

Citrate-based Regional Anticoagulation Versus Heparin for Continuous Renal Replacement Therapy in Critically Ill Patients With Acute Renal Failure: a Randomized Controlled Trial

Critically ill patients with acute kidney injury (AKI) are at high risk of bleeding on account of coagulopathy, platelet dysfunction, frequent liver dysfunction and invasive procedures.In patients at high risk of bleeding, anticoagulation restricted to the circuit (regional anticoagulation) has been advocated as the method of choice.However, citrate anticoagulation may have many metabolic consequences, such as metabolic alkalosis due to citrate metabolism into bicarbonate, and in patients with liver disease, metabolic acidosis and hypocalcemia may occur.Implementation of citrate-based regional anticoagulation with frequent monitoring of acid-base and electolytes is also more challenging for the nurses and does not eliminate the need of a low-dose systemic anticoagulation for thromboses prophylaxis in most of the patients. Citrate-based regional anticoagulation is therefore mainly advocated only for patients at high-risk of bleeding.

The investigators plan to implement an open-label randomized control trial assessing the effectiveness of citrate-based regional anticoagulation in critically ill patients with AKI and with a special emphasis on the safety profile of this treatment in patients with severe liver failure.

Study Overview

• Status: Completed
• Conditions: Acute Kidney Injury
• Intervention / Treatment: Device: citrate regional anticoagulation

Detailed Description

monocentric prospective open-label randomized controlled trial at the ICU of the University Hospitals of Geneva (Switzerland).

ICU patients eligible if they 18 yr old and had an AKI requiring CRRT Exclusion criteria Patients excluded if they had active hemorrhagic disorders or severe thrombocytopenia (< 50x109/L), a history of heparin-induced thrombocytopenia, severe liver failure defined as a factor V <20% or were on the waiting list for liver transplantation.

Treatment assignment Subjects enrolled into the trial randomly allocated to either heparin or citrate anticoagulation

• Study Type: Interventional
• Enrollment (Actual): 103
• Phase: Phase 4

Contacts and Locations

Study Locations

• Switzerland
  • Geneva, Switzerland, 1211
    • University Hospitals of Geneva

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients with acute kidney injury requiring renal replacement therapy (RIFLE criteria)
• Patients (males or females) > 18 yrs old
• Consent form signed (or in emergency investigator's statement form)

Exclusion Criteria:

• Patients with active bleeding disorders
• Patients with past history of heparin-induced thrombocytopenia (HIT)
• Patients with very severe liver disease ( patients awaiting liver transplant or factor V < 20% or MELD score > 25)
• Pregnancy (negative pregnancy test required in child-bearing age women prior to inclusion)
• Enrollment in another concurrent therapeutic trial

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
PLACEBO_COMPARATOR: heparin; CVVHDF performed using unfractionated heparin as anticoagulant and Prismasol as reinjection and dialysate fluids	Device: citrate regional anticoagulation; Patients randomly allocated to 2 treatment groups: Treatment A: - Regional citrate-based anticoagulation with the Prismocitrate® 10/2 solution (GAMBRO) Treatment B: - Standard unfractionated heparin anticoagulation
ACTIVE_COMPARATOR: citrate regional anticoagulation; CVVHDF performed using Prismocitrate 18/0 solution (Trisodium citrate 18 mmol/L	Device: citrate regional anticoagulation; Patients randomly allocated to 2 treatment groups: Treatment A: - Regional citrate-based anticoagulation with the Prismocitrate® 10/2 solution (GAMBRO) Treatment B: - Standard unfractionated heparin anticoagulation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean daily dialysis delivered dose during intensive care stay	Mean daily delivered dose during intensive care stay; Filter life span	dialysis days during intensive care stay

Secondary Outcome Measures

Outcome Measure	Time Frame
patient survival	28-day and 90-day patient survivals

Collaborators and Investigators

• Sponsor: University Hospital, Geneva

Publications and helpful links

General Publications

• Tsujimoto H, Tsujimoto Y, Nakata Y, Fujii T, Takahashi S, Akazawa M, Kataoka Y. Pharmacological interventions for preventing clotting of extracorporeal circuits during continuous renal replacement therapy. Cochrane Database Syst Rev. 2020 Dec 14;12(12):CD012467. doi: 10.1002/14651858.CD012467.pub3.
• Stucker F, Ponte B, Tataw J, Martin PY, Wozniak H, Pugin J, Saudan P. Efficacy and safety of citrate-based anticoagulation compared to heparin in patients with acute kidney injury requiring continuous renal replacement therapy: a randomized controlled trial. Crit Care. 2015 Mar 18;19(1):91. doi: 10.1186/s13054-015-0822-z.

Study record dates

Study Major Dates

• Study Start: November 1, 2010
• Primary Completion (ACTUAL): July 1, 2013
• Study Completion (ACTUAL): November 1, 2013

Study Registration Dates

• First Submitted: January 3, 2011
• First Submitted That Met QC Criteria: January 3, 2011
• First Posted (ESTIMATE): January 4, 2011

Study Record Updates

• Last Update Posted (ACTUAL): August 14, 2019
• Last Update Submitted That Met QC Criteria: August 13, 2019
• Last Verified: May 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Kidney Diseases; Urologic Diseases; Renal Insufficiency; Acute Kidney Injury; Molecular Mechanisms of Pharmacological Action; Anticoagulants; Chelating Agents; Sequestering Agents; Calcium Chelating Agents; Citric Acid; Sodium Citrate
• Other Study ID Numbers: 09-069(NAC 09-27)