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Trial record 70 of 109 for:    CALCIUM CATION

Regional Anticoagulation of Dialysis Circuits With a Calcium-free Citrate-containing Dialysate (C2D)

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ClinicalTrials.gov Identifier: NCT03842657
Recruitment Status : Recruiting
First Posted : February 15, 2019
Last Update Posted : August 21, 2019
Sponsor:
Information provided by (Responsible Party):
University Hospital, Toulouse

Tracking Information
First Submitted Date  ICMJE January 29, 2019
First Posted Date  ICMJE February 15, 2019
Last Update Posted Date August 21, 2019
Actual Study Start Date  ICMJE July 5, 2019
Estimated Primary Completion Date July 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 12, 2019)
  • Premature termination of the first dialysis session (<4 hours) related to a coagulation of the dialysis circuit [ Time Frame: Visite T1 (3 days maximum after inclusion visit) ]
    Premature termination of the dialysis session (<4 hours) in connection with coagulation or pre-coagulation state of the dialysis circuit (thrombosis global index strictly greater than 1 (visual assessment) or elevation of transmembrane pressure above 350 mmHg)
  • Premature termination of the second dialysis session (<4 hours) related to a coagulation of the dialysis circuit [ Time Frame: Visite T2 (7 days maximum after inclusion visit) ]
    Premature termination of the dialysis session (<4 hours) in connection with coagulation or pre-coagulation state of the dialysis circuit (thrombosis global index strictly greater than 1 (visual assessment) or elevation of transmembrane pressure above 350 mmHg)
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT03842657 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: February 12, 2019)
  • Hemodynamic tolerance [ Time Frame: Visite T1 (3 days maximum after inclusion visit), Visite T2 (7 days maximum after inclusion visit) ]
    Number of cardiovascular events during the dialysis session
  • Clinical tolerance [ Time Frame: Visite T1 (3 days maximum after inclusion visit), Visite T2 (7 days maximum after inclusion visit) ]
    Clinical symptoms collected every 30 min on patient
  • Biological tolerance [ Time Frame: Visite T1 (3 days maximum after inclusion visit), Visite T2 (7 days maximum after inclusion visit) ]
    Measurement of total and ionized calcium and venous pH sampled on the arterial branch of the dialysis circuit
  • Systemic inflammation [ Time Frame: Visite T1 (3 days maximum after inclusion visit), Visite T2 (7 days maximum after inclusion visit) ]
    To determine the serum levels of cytokines (interleukine-6, interferon-γ, MCP1, Tumor Necrosis Factor-α) by ELISA.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Regional Anticoagulation of Dialysis Circuits With a Calcium-free Citrate-containing Dialysate
Official Title  ICMJE Regional Anticoagulation of Dialysis Extra-corporeal Circuits With a Calcium-free Citrate-containing Dialysate : Efficiency and Tolerance
Brief Summary Critically ill patients have a high risk of bleeding but also require prolonged intermittent dialysis. Thus, a heparin-free easy-to-use alternative type of anticoagulation within the dialysis circuit is required. In a non-comparative study, heparin-free regional citrate anticoagulation of the dialysis circuit using a calcium-free citrate-containing dialysate, with calcium reinjected according to ionic dialysance, was considered as safe and efficient. The aim of this study is to confirm the superiority of this approach compared to a anticoagulation based on heparin-grafted membrane.
Detailed Description

Critically ill patients have a high risk of bleeding but also require prolonged intermittent dialysis. Several modalities are used for heparin-free dialysis sessions. Iterative saline infusion and heparin-grafted membranes are easy to use and remain the standards-of-care for high-risk bleeding situations but efficiency is low: success rates from hemodialysis sessions range from 50% to 65% and 50% to 75%, respectively. Furthermore, sessions that last for greater than 240 minutes are rarely achievable and can be problematic when ensuring an adequate dose of dialysis and a negative water balance in patients who cannot tolerate a high ultrafiltration rate. Thus, the development of alternative regional anticoagulation methods is needed urgently to improve intermittent hemodialysis (IHD) in critically ill patients and to avoid systemic anticoagulation in patients with a high risk of bleeding.

An easy way to provide citrate inside the filter, to lower iCa below 0.45 mmol/L could be to use diffusive influx from the dialysate. It has been demonstrated recently that the use of citric acid as the acidic component of dialysate can enable a dose reduction of heparin and increase the efficiency of hemodialysis. However, the amount of citrate (0.8 mmol/L) and calcium (1.25-1.75 mmol/L) contained in this dialysate do not allow the target of iCa to be reached in the ECC. In contrast, a citrate dialysate that contains no calcium would provide enough calcium-free transfer to lower iCa below 0.45 mmol/L; however, a problem would be the large amount of calcium loss during the session.

Pivotal studies show that, during dialysis sessions performed with calcium-free dialysate, the rate of calcium reinjection required to compensate for calcium loss in the dialysate can be easily deducted from the ionic dialysance (ID), which is an online measurement of instantaneous small solute clearance, available from most dialysis monitors. ID has been also used as a surrogate marker for dialysis dose in ICU patients receiving IHD. Thus, the use of calcium-free citrate-containing dialysate with calcium reinjection according to ID could provide enough citrate to prevent coagulation within the filter, and calcium restitution can then be monitored by online ID without the need for systemic measurement of iCa. It may also improve the hemodynamic tolerance of IHD by avoiding acetate in the dialysate.

The objective of the present study was to show the efficiency of this approach using RCA for dialysis sessions (<4 hrs) of IHD in patients with moderate to high risk of bleeding, based on the success rate of hemodialysis without clotting. Each patient included in this study will receive two heparin-free dialysis sessions with heparin-grafted membrane (control group) or RCA with calcium-free citrate-containing dialysate and calcium reinjection according to the ionic dialysance (experimental group), alternatively. The order of anticoagulation will be randomized.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Hemodialysis Complication
  • Bleeding
Intervention  ICMJE Combination Product: anticoagulation of the dialysis circuit
Each patient included in this study will receive two heparin-free dialysis sessions with heparin-grafted membrane (control group) or RCA with calcium-free citrate-containing dialysate and calcium reinjection according to the ionic dialysance (experimental group), alternatively
Study Arms  ICMJE
  • calcium-free citrate-containing dialysate
    Dialysis session will be performed with a non-heparin grafted membrane, a dialysate without calcium (0 mmol/L) and citrate 0.8 mmol/L, a reinjection of a calcium solution (300 mM) according to the ionic dialysance, and no heparin addition
    Intervention: Combination Product: anticoagulation of the dialysis circuit
  • heparin-grafted membrane
    dialysis session will be performed with a heparin-grafted membrane, a dialysate with calcium (1.65 mmol/L) and citrate 0.8 mmol/L, and no heparin addition
    Intervention: Combination Product: anticoagulation of the dialysis circuit
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: February 12, 2019)
97
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE July 2021
Estimated Primary Completion Date July 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria: will be included in the study, patients

  • hat require two sessions of dialysis that last for greater than 240 minutes in the 7 days following the inclusion.
  • With a moderate to high risk of bleeding (platelets count below 150.000/mm3; platelet disorders; bleeding in the last 10 days, surgery or biopsy in the last 10 days or planned in the next 7 days; admission to the ICU)
  • Older than 18 years of age
  • That gave written informed consent

Exclusion Criteria: will be excluded from the study, patients with

  • Heparin allergy
  • On-going treatment by vitamin-K antagonists (INR > 1.2) or unfractionated heparin (anti-Xa activity > 0.10)..
  • Known allergy to the Evodial (Baxter, France) or Cordiax FX100 (Fresenius, France) membranes
  • On-going treatment by angiotensin converting enzyme inhibitors
  • Pregnancy or risk of pregnancy
  • Patient under guardianship
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Stanislas FAGUER, MD 05 61 32 24 75 ext 33 faguer.s@chu-toulouse.fr
Listed Location Countries  ICMJE France
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03842657
Other Study ID Numbers  ICMJE RC31/17/0451
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party University Hospital, Toulouse
Study Sponsor  ICMJE University Hospital, Toulouse
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Stanislas FAGUER, MD University Hospital, Toulouse
PRS Account University Hospital, Toulouse
Verification Date August 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP