- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT05814341
Citrate Anticoagulation in Renal Replacement Therapy: Impact of a High Post-filter Calcium Target on Efficacy (Ca-CIBLE)
July 24, 2023 updated by: Assistance Publique - Hôpitaux de Paris
The Effect of Increasing Post-Filter Ionized Target on the Efficacy of Regional Citrate Anticoagulation During Continuous Renal Replacement Therapy in Intensive Care: a Multicenter Randomized Controlled Non-Inferiority Trial
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.
Study Overview
Detailed Description
RCA-CRRT will be ordered based on clinical indications and will be performed according to a standardized protocol (available as online supplementary material) in continuous veno-venous hemofiltration mode with the same system (Prismaflex®; Gambro-Baxter, Deerfield, IL, USA) and a 0.9 m2 high-flux AN69 membrane.
Blood flow will be maintained between 120 and 180 mL/min according to the patient's ideal body weight.
The prescribed dose of filtration will be 30 mL/kg/h to achieve a delivered dose of 20-25 mL/kg/h, following KDIGO guidelines.
A citrated replacement solution (Regiocit®; Gambro-Baxter), containing 18.0 mmol/L of citrate, will be delivered continuously to the blood before the filter of the extracorporeal circuit.
The rate of infusion of predilution replacement flow will be coupled to the blood flow, aiming for a stable citrate concentration in the extracorporeal circuit.
The initial citrate dose will be 3.0 mmol/L of blood, and then citrate flow rate will be adjusted to the post-filter iCa target according to the protocol.
Post-filter iCa will be measured on ABL90 FLEX PLUS™ (Radiometer Medical©, Copenhagen, Denmark) blood gas analyzer 15 minutes after any change in dose and then every 6 hours.
Calcium chloride will be administered to the patient through a central line to maintain systemic-iCa within 1.00-1.30
mmol/L.
Fluid removal rates will be left to the discretion of the attending physician in order to achieve optimal fluid balance.
Additionally, metabolic monitoring will be carried out by a blood ionogram every 12 hours.
The quantitative parameters will be presented as median and interquartile range [IQR], and comparisons will be made using either Student's t-test or the Mann-Whitney U test depending on whether the assumptions of the t-test are met or not.
Categorical data will be reported as the number and percentage (%) and will be compared using Fisher's exact or chi-square test, as appropriate.
The incidence of filter clotting will be expressed in absolute values (n) and percentage (%).
Comparison between groups will be performed using Pearson's Chi-square test.
The analysis of the primary endpoint will be conducted on a per-protocol basis as a first intention (the most conservative approach in a non-inferiority study) and on an intention-to-treat basis.
Filter lifespan until clotting curves according to the post-filter iCa2 target will be plotted using the Kaplan-Meier method and compared using the log-rank test.
Study Type
Interventional
Enrollment (Estimated)
412
Phase
- Phase 3
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Contact
- Name: Mona ASSEFI, Dr
- Phone Number: 01 84 82 73 59
- Email: mona.assefi@aphp.fr
Study Contact Backup
- Name: Jean Michel CONSTANTIN, Pr
- Phone Number: 01 42 17 73 05
- Email: jean-michel.constantin@aphp.fr
Study Locations
-
-
-
Paris, France, 75013
- Recruiting
- Hospital Pitie Salpetriere
-
Contact:
- Mona ASSEFI, Dr
- Phone Number: 01 84 82 73 59
- Email: mona.assefi@aphp.fr
-
-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
- Adult
- Older Adult
Accepts Healthy Volunteers
No
Description
Inclusion Criteria:
- 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)
- Having given their written consent or, if the patient is unable to consent and is accompanied, written consent from or legal representative or the close relative. If the patient is unable to consent and is not accompanied, due to the urgency of the procedure, the patient can also be included on the decision of the investigator (inclusion procedure in an emergency situation with subsequent necessity to sign a consent to prosecute).
Exclusion Criteria:
- 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 -
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: High iCa target
Post-filter iCa between 0,35-0.45
mmol/L
|
Comparison of two dosage adjustment protocols for medication according to different post-filter iCa targets
Other Names:
|
Active Comparator: Low iCa target
Post-filter iCa between 0.25-0.35
mmol/L
|
Comparison of two dosage adjustment protocols for medication according to different post-filter iCa targets
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Incidence of filter clotting
Time Frame: 72 hours
|
Filter clotting was defined by increased transmembrane pressure greater than 300 mmHg
|
72 hours
|
Incidence of filter clotting
Time Frame: 72 hours
|
Filter clotting was defined by visible thrombus in circuit or filter
|
72 hours
|
Incidence of filter clotting
Time Frame: 72 hours
|
Filter clotting was defined by inability to rotate the blood pump due to an obstructing thrombus
|
72 hours
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Filter lifespan until clotting and filter lifespan, including all causes of stoppage
Time Frame: 72 hours
|
The lifespan of each hemofilter measured in hours.
The cause of CRRT discontinuation will be defined by filter clotting
|
72 hours
|
Filter lifespan until clotting and filter lifespan, including all causes of stoppage
Time Frame: 72 hours
|
The lifespan of each hemofilter measured in hours.
The cause of CRRT discontinuation will be defined by catheter dysfunction : excessively negative inlet pressure (less than -150mmHg) or excessively positive outlet pressure (greater than +150mmHg)
|
72 hours
|
Filter lifespan until clotting and filter lifespan, including all causes of stoppage
Time Frame: 72 hours
|
The lifespan of each hemofilter measured in hours.
The cause of CRRT discontinuation will be defined by transport: removal of the patient for mobilization
|
72 hours
|
Filter lifespan until clotting and filter lifespan, including all causes of stoppage
Time Frame: 72 hours
|
The lifespan of each hemofilter measured in hours.
The cause of CRRT discontinuation will be defined by futility: no indication to continue CRRT
|
72 hours
|
Filter lifespan until clotting and filter lifespan, including all causes of stoppage
Time Frame: 72 hours
|
The lifespan of each hemofilter measured in hours.
The cause of CRRT discontinuation will be defined by end of session: CRRT has been ongoing for more than 72 hours
|
72 hours
|
Filter lifespan until clotting and filter lifespan, including all causes of stoppage
Time Frame: 72 hours
|
The lifespan of each hemofilter measured in hours.
The cause of CRRT discontinuation will be defined by citrate accumulation
|
72 hours
|
Filter lifespan until clotting and filter lifespan, including all causes of stoppage
Time Frame: 72 hours
|
The lifespan of each hemofilter measured in hours.
The cause of CRRT discontinuation will be defined by Intensive Care Unit discharge
|
72 hours
|
Filter lifespan until clotting and filter lifespan, including all causes of stoppage
Time Frame: 72 hours
|
The lifespan of each hemofilter measured in hours.
The cause of CRRT discontinuation will be defined by death
|
72 hours
|
Proportion of post-filter iCa in the target range and last psot-filter iCa value before clotting
Time Frame: 72 hours
|
Post-filter iCa levels (in mmol/L) measured during the CRRT session
|
72 hours
|
Total dose of citrate infused
Time Frame: 72 hours
|
Citrate infusion rates, in mmol/day
|
72 hours
|
Incidence of metabolic events (hypocalcemia, metabolic acidosis, metabolic alkalosis, hypernatremia, hypomagnesemia, citrate accumulation)
Time Frame: 72 hours
|
The occurrence of the following 6 metabolic complications:
|
72 hours
|
Financial costs associated with filter changes and citrate use
Time Frame: 72 hours
|
The costs (in euros) incurred by each filter change and the amount of citrate infused
|
72 hours
|
Blood loss during the procedure
Time Frame: 72 hours
|
Inability to return the CRRT circuit at the end of the session (equivalent to 200mL of blood loss)
|
72 hours
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Investigators
- Principal Investigator: Mona ASSEFI, Dr, Hôpital Pitié Salpêtrière - Assistance Publique Hôpitaux de Paris
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
July 1, 2023
Primary Completion (Estimated)
January 1, 2025
Study Completion (Estimated)
February 2, 2025
Study Registration Dates
First Submitted
April 3, 2023
First Submitted That Met QC Criteria
April 3, 2023
First Posted (Actual)
April 14, 2023
Study Record Updates
Last Update Posted (Actual)
July 25, 2023
Last Update Submitted That Met QC Criteria
July 24, 2023
Last Verified
July 1, 2023
More Information
Terms related to this study
Keywords
Other Study ID Numbers
- APHP220257
- 2022-003678-22 (Other Identifier: ANSM)
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
No
Studies a U.S. FDA-regulated device product
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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