Trial Review

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT04755491




Registration number
NCT04755491
Ethics application status
Date submitted
11/02/2021
Date registered
16/02/2021
Date last updated
13/09/2022

Titles & IDs
Public title
Chloride Transfer During Continuous Renal Replacement Therapy in the Intensive Care Unit: a Prospective Observational Cohort Study
Scientific title
Chloride Transfer During Continuous Renal Replacement Therapy in the Intensive Care Unit: a Prospective Observational Cohort Study
Secondary ID [1] 0 0
69HCL20_1055
Universal Trial Number (UTN)
Trial acronym
CLODICUS
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Acute Kidney Injury 0 0
Condition category
Condition code
Renal and Urogenital 0 0 0 0
Kidney disease
Injuries and Accidents 0 0 0 0
Other injuries and accidents

Intervention/exposure
Study type
Observational
Patient registry
Target follow-up duration
Target follow-up type
Description of intervention(s) / exposure
Treatment: Devices - Continuous veno-venous hemofiltration
Treatment: Devices - Continuous veno-venous hemodialysis
Treatment: Devices - Continuous veno-venous hemodiafiltration

Chloride transfer by continuous veno-venous hemofiltration - Chloride transfer over 24h of continuous veno-venous hemofiltration in mechanically ventilated ICU patients presenting with stage III AKI according to Kidney Disease: Improving Global Outcome (KDIGO) classification. Chloride concentrations will be measured in the serum, the urine, and the effluent of included patients every 4 to 6h from inclusion to H24.

Chloride transfer by continuous veno-venous hemodialysis - Chloride transfer over 24h of continuous veno-venous hemodialysis in mechanically ventilated ICU patients presenting with stage III AKI according to Kidney Disease: Improving Global Outcome (KDIGO) classification. Chloride concentrations will be measured in the serum, the urine, and the effluent of included patients every 4 to 6h from inclusion to H24.

Chloride transfer by continuous veno-venous hemodiafiltration - Chloride transfer over 24h of continuous veno-venous hemodiafiltration in mechanically ventilated ICU patients presenting with stage III AKI according to Kidney Disease: Improving Global Outcome (KDIGO) classification. Chloride concentrations will be measured in the serum, the urine, and the effluent of included patients every 4 to 6h from inclusion to H24.


Treatment: Devices: Continuous veno-venous hemofiltration
Treatment of KDIGO stage 3 AKI by CVVH, in which renal replacement therapy is applied using a convection technique (ultrafiltration). Indication, choice of CRRT modality, and CRRT settings are made by the clinician in charge, following international recommendations. The measurement of chloride transfer over 24h is performed during CVVH treatment.

Treatment: Devices: Continuous veno-venous hemodialysis
Treatment of KDIGO stage 3 AKI by CVVD, in which renal replacement therapy is applied using a diffusion technique (dialysis). Indication, choice of CRRT modality, and CRRT settings are made by the clinician in charge, following international recommendations. The measurement of chloride transfer over 24h is performed during CVVD treatment.

Treatment: Devices: Continuous veno-venous hemodiafiltration
Treatment of KDIGO stage 3 AKI by CVVHDF, in which renal replacement therapy is applied using a combination of diffusion technique (dialysis) and convection technique (ultrafiltration). Indication, choice of CRRT modality, and CRRT settings are made by the clinician in charge, following international recommendations. The measurement of chloride transfer over 24h is performed during CVVHDF treatment.
Intervention code [1] 0 0
Treatment: Devices
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Amount of chloride (in mmol) transferred to the patient during the first 24 hours of RRT following inclusion
Timepoint [1] 0 0
24 hours after inclusion

Eligibility
Key inclusion criteria
- Adult patients (age > 18 years) affiliated to a social security regimen.

- Presenting with stage III AKI according to Kidney Disease: Improving Global Outcome
(KDIGO) classification28.

- Treated with continuous RRT (CVVH or CVVD or CVVHDF) for less than 24 hours, whatever
the method used.

- Mechanically ventilated at the time of inclusion in the study.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Patients on chronic hemodialysis / peritoneal dialysis.

- Patients on extracorporeal membrane oxygenation

- Patients on intermittent hemodialysis (acute or chronic)

- RRT initiated for a different reason than stage III AKI according to Kidney Disease:
Improving Global Outcome (KDIGO) classification

- Withholding of life sustaining treatment concerning RRT, mechanical ventilation or
cardiopulmonary resuscitation.

- Patients whose life expectancy is lower than 24 hours

- Patients under guardianship or another juridical protection

- Patient's or next of kin opposition to participate

- Patients previously included in the study

Study design
Purpose
Duration
Selection
Timing
Prospective
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
16/03/2021
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
24/08/2022
Sample size
Target
Accrual to date
Final
50
Recruitment in Australia
Recruitment state(s)
Recruitment outside Australia
Country [1] 0 0
France
State/province [1] 0 0
Lyon

Funding & Sponsors
Primary sponsor type
Other
Name
Hospices Civils de Lyon
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Acute kidney injury (AKI) is a frequently encountered complication in the intensive care unit
(ICU), affecting on average 25 to 35% of patients. It is associated with an increased
mortality, proportional to AKI severity. RRT induces important shifts of water and
electrolytes. Thus, significant amount of chloride might unintentionally be transferred to
patients.

Chloride is the main anion of the organism. It is involved in the regulation of numerous
physiological processes. Thus, significant and rapid modification of chloride amount
contained in the organism (as might be induced by renal replacement therapy) may be
responsible for important, and potentially deleterious, consequences to critically ill
patients.

Studies have shown that the administration of high amounts of chloride rich solutions (such
as sodium chloride (NaCl) 0,9%) was associated with the development of hyperchloremic
acidosis in a dose-dependent manner. This hyperchloremic acidosis could also be theoretically
associated with deleterious physiological effects. However, the true clinical consequences of
administration of high amounts of chloride rich solutions remains unclear. Their effect on
mortality remains a matter of debate, the results of studies being very conflicting in that
respect. Nevertheless, hyperchloremia itself and/or the rise of chloremia in the intensive
care unit seems to be associated with increased mortality. Moreover, the impact of those
chloride rich solutions on the development of acute kidney injury is also a subject of
controversy, data from the literature being here again very conflicting.

A recent study already showed that continuous RRT (CRRT) techniques induce a significant
transfer of sodium to patients benefiting from those techniques. In that study, the amount of
sodium transferred depended mainly on the difference between patient's natremia and sodium
concentration in dialysate and/or replacement fluid (usually higher than patient's natremia)
used.

By analogy, it is likely that an occult transfer of chloride also happens during RRT, given
the high chloride concentration of dialysate fluids (in continuous veno-venous dialysis,
CVVD) and replacement fluids (in continuous veno-venous hemofiltration, CVVH), or when these
2 modalities are combined (continuous veno-venous hemodiafiltration, CVVHDF). Finally, the
investigators suspect, although it remains undemonstrated so far, that the RRT technique
(convective vs. diffusive) may influence this transfer, to an unknown extent. Nevertheless,
this transfer and its potential determinants have never been studied yet.

If chloride overload (and its potential clinical consequences) induced by the administration
of solutions such as NaCl 0,9% is being extensively studied, no study has ever focused on
chloride transfer that may result from the use of renal replacement therapy. However, as
mentioned above, it is very likely that such a chloride transfer to patients happens, and
that its magnitude depends on different parameters such as RRT modality, RRT fluids
characteristics, or patient's chloremia at the start of RRT.

The investigators conduct the present study to describe and compare the intensity of chloride
transfer during the first 24 hours of renal replacement therapy by continuous veno-venous
hemofiltration (CVVH), continuous veno-venous hemodialysis (CVVD),or continuous veno-venous
hemodiafiltration (CVVHDF), and to determine if that transfer is more important with one or
the other of those two techniques, in ICU patients affected with severe AKI requiring RRT.
Secondary aims are to describe and compare the effects of chloride transfer under 3 RRT
modalities (CVVD, CVVH and CVVHDF) on patient's outcome, organ failures, electrolyte and
acid-base balance, fluid balance and hemodynamics. Finally, the investigators aim to develop
a pharmacokinetic compartment model of chloride transfer during different modalities of RRT.
Trial website
https://clinicaltrials.gov/ct2/show/NCT04755491
Trial related presentations / publications
Public notes
This record is viewable in the ANZCTR as it had previously listed Australia and/or New Zealand as a recruitment site, however these sites have since been removed

Contacts
Principal investigator
Name 0 0
Laurent BITKER, MD, PhD
Address 0 0
Hospices Civils de Lyon
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT04755491