Citrate Anticoagulation in Renal Replacement Therapy: Impact of a High Post-filter Calcium Target on Efficacy

NCT05814341 | Completed Phase 3

• 2 other identifiers: APHP2202572022-003678-22
• Study Type: interventional
• Target: 108
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Renal Replacement Therapy

Keywords

Acute kidney injury; Continuous renal replacement therapy; Regional citrate anticoagulation; Ionized calcium; Intensive care

Outcome Measures

Primary Outcomes (3)

• Incidence of filter clotting

  Filter clotting was defined by increased transmembrane pressure greater than 300 mmHg

  72 hours

• Incidence of filter clotting

  Filter clotting was defined by visible thrombus in circuit or filter

  72 hours

• Incidence of filter clotting

  Filter clotting was defined by inability to rotate the blood pump due to an obstructing thrombus

  72 hours

Secondary Outcomes (13)

• Filter lifespan until clotting and filter lifespan, including all causes of stoppage

  72 hours

• Filter lifespan until clotting and filter lifespan, including all causes of stoppage

  72 hours

• Filter lifespan until clotting and filter lifespan, including all causes of stoppage

  72 hours

• Filter lifespan until clotting and filter lifespan, including all causes of stoppage

  72 hours

• Filter lifespan until clotting and filter lifespan, including all causes of stoppage

  72 hours

Study Arms (2)

High iCa target

EXPERIMENTAL

Post-filter iCa between 0,35-0.45 mmol/L

Drug: Citrate

Low iCa target

ACTIVE COMPARATOR

Post-filter iCa between 0.25-0.35 mmol/L

Drug: Citrate

Interventions

Citrate DRUG

Comparison of two dosage adjustment protocols for medication according to different post-filter iCa targets

Also known as: REGIOCIT®

High iCa target; Low iCa target

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 18 years old
• Hospitalized in intensive care and presenting an indication for extra renal replacement therapy with Regional citrate anticoagulation (RCA)
• Patients covered by social security regimen (excepting AME)

You may not qualify if:

• Patients receiving curative systemic anticoagulation
• Patients with a contraindication to the use of citrate : - Hypersensitivity to Regiocit®
• Patients with a contraindication to the administration of the ancillary drugs Phoxilium® and calcium chloride
• 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)
• Pregnant woman
• People under legal protection measure (guardianship or safeguard measures)
• A patient legal representative or the close relative who declined to participate
• Patient deprived of liberty by a judicial or administrative decision
• Patient participating to another interventional study that may have an impact on the evaluation criteria of this study -

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead

Study Sites (1)

Hospital Pitie Salpetriere

Paris, 75013, France

Location

Related Publications (1)

• Assefi M, Braik R, James A, Clavieras N, Baron E, Blanchard F, Constantin JM. Impact of increasing post-filter ionised calcium target on regional citrate anticoagulation efficacy in ICU continuous renal replacement therapy: the non-inferiority randomised controlled Ca-CIBLE protocol. BMJ Open. 2024 Sep 26;14(9):e081325. doi: 10.1136/bmjopen-2023-081325.

  PMID: 39327056 DERIVED

MeSH Terms

Conditions

Acute Kidney Injury

Interventions

Citric Acid

Condition Hierarchy (Ancestors)

Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Citrates; Tricarboxylic Acids; Acids, Acyclic; Carboxylic Acids; Organic Chemicals

Study Officials

• Mona ASSEFI, Dr

  Hôpital Pitié Salpêtrière - Assistance Publique Hôpitaux de Paris

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 3, 2023
• First Posted: April 14, 2023
• Study Start: July 1, 2023
• Primary Completion: December 15, 2024
• Study Completion: December 15, 2024
• Last Updated: August 22, 2025

Record last verified: 2024-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Beginning 3 months and ending 3 years following article publication. Requests out of these time frame can also be submitted to the sponsor
• Access Criteria: Researchers who provide a methodologically sound proposal

Locations

FR (1)