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A Study on the Efficacy and Safety of Continuous Renal Replacement Therapy (CVVHDF) Using a Commercial Citrate-containing Replacement Fluid (Prismocitrate 18/0)

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ClinicalTrials.gov Identifier: NCT01921816
Recruitment Status : Completed
First Posted : August 13, 2013
Last Update Posted : December 3, 2014
Sponsor:
Information provided by (Responsible Party):
Lui Mei Sze, Queen Mary Hospital, Hong Kong

Brief Summary:
The investigators aim to examine the efficacy and safety of using a new citrate containing commercially available solutions (Prismocitrate 18/0) as the regional citrate anticoagulation in continuous renal replacement therapy for critically ill patients.

Condition or disease Intervention/treatment Phase
Renal Failure Device: Prismocitrate 18/0, Prism0cal Not Applicable

Detailed Description:

Acute kidney injury is common in critically ill patients, and continuous renal replacement therapy is the preferable mode of treatment to remove the metabolic waste while avoiding the hemodynamic instability associated with intermittent hemodialysis. Thrombosis frequently occurs in the hemofilter which could reduce the circuit lifespan, jeopardize the efficacy of renal replacement, result in loss of blood cells and increased transfusion requirement. Anticoagulants including conventional heparin and low molecular weight heparin, introduced via the arterial port of the circuit, are widely used to reduce clotting within the extracorporeal circuit. However, significant amount of heparin is not removed in the circuit and will be carried into patient's circulation, which could lead to bleeding complications. Regional citrate anticoagulation (RCA) has been used for intermittent haemodialysis since 1983, and its use has extended to that for continuous renal replacement therapy (CRRT) since 1987. Citrate is introduced at therapeutic level at the arterial limb of the dialysis circuit, where it chelates calcium ions in the blood to prevent clotting within the hemofilter. While some calcium-citrate complex is removed in the filter, the residual will be circulated to the patient and be metabolized in liver. Patient's systemic ionized calcium level remains normal, by hemodilution and also calcium replacement. Therefore, the anticoagulant effect from citrate is regional and confined to the extracorporeal circuit. RCA has the potential to extend circuit life during renal replacement therapy without systemic anticoagulation. In a recent meta-analysis of randomized controlled trials, RCA was as efficacious as heparin anticoagulation in term of maintaining circuit function, and RCA was associated with decreased risk of bleeding with no significant increase in incidence of metabolic alkalosis.(5) Hypocalcemia was more common in patients receiving citrate, but of note, no clinical adverse event was reported in the included studies. Although citrate anticoagulation had repeatedly been demonstrated to prolong filter life, many hospitals still refrained from using it, as a result of limited experience, different patient variety, or other reasons.

The investigators' group has performed a pilot study (HKU/HA HKW IRB No: UW 08-221) to assess the efficacy and safety of continuous venous-venous hemodiafiltration(CVVHDF) using a commercial citrate containing replacement fluid (Prismocitrate 10/2, Gambro) which contains 10mmol/l citrate and 2 mmol/l citric acid. 15 subjects were recruited from July 2008 to June 2011. No serious adverse events were reported, including severe hypocalcemia, hypercalcemia, citrate toxicity and severe acid base disturbances. Metabolic acidosis due to renal failure were only partially corrected by CRRT with citrate anticoagulation in the initial study subjects, the problem was subsequently solved by adding supplemental bicarbonate to the dialysate. Since then, all the patients were able to complete the treatment protocols with adequate kidney lifespan, correction of metabolic abnormalities and fluid imbalance. However, since additional bicarbonate is needed to correct the metabolic acidosis during CRRT, there is room for improvement regarding the formulation of the citrate-containing solution to reduce acid liberation while increasing the alkali bicarbonate production. Prismocitrate 18/0, which contains 18mmol/l citrate (one mmol citrate could be metabolized to produce 3 mmol bicarbonate) and no citric acid, could potentially result in better acid-base control during CRRT.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 35 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Supportive Care
Study Start Date : May 2012
Actual Primary Completion Date : August 2013

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Prismocitrate 18/0
citrate-containing replacement solution (Prismocitrate 18/0, Gambro) will be administered at pre-filter port during continuous hemodiafiltration, for the purpose as replacement solution and anticoagulation
Device: Prismocitrate 18/0, Prism0cal
Subjects on continuous hemodiafiltration will ordinarily receive heparin as the anticoagulation. In our study, regional citrate anticoagulation with Prismacitrate is used to replace heparin. Citrate has been shown in study to be safer than heparin with reduced bleeding risk
Other Name: Prismocitrate 18/0 (replacement solution), Prism0cal (dialysate), Gambro




Primary Outcome Measures :
  1. filter lifespan [ Time Frame: up to 4 days ]
    filter lifespan will be recorded as the time duration from commencement of renal replacement therapy till filter clotted or therapy ended


Secondary Outcome Measures :
  1. metabolic and electrolyte control [ Time Frame: up to 4days ]
    Serum electrolytes (calcium, sodium, potassium, magnesium, acid-base)will be monitored at baseline, then every 6 hours onwards during the CRRT

  2. bleeding/transfusion requirement [ Time Frame: up to 4 days ]
    blood counts including the hemoglobin level and patient clinical status will be monitored at baseline, then once everyday during renal replacement therapy



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Ages Eligible for Study:   18 Years to 90 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • The patient requires CRRT as treatment for renal failure, as decided by the attending physician
  • The patient fulfils at least one of the following clinical criteria for initiating CRRT:

    1. According to the RIFLE criteria, (11) patients satisfying the "injury" criteria (increase creatinine by 2 fold or urine output<0.5ml/kg/hr for 12hr) will be considered for CRRT
    2. Hyperkalemia ([K+] > 6.5 mmol/L).
    3. Severe acidemia (pH < 7.2).
    4. Urea > 25 mmol/liter.
    5. Clinically significant organ oedema in the setting of ARF.

      Exclusion Criteria:


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01921816


Locations
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Hong Kong
Adult Intensive Care unit, Queen Mary Hospital
Hong Kong, Hong Kong, 852
Sponsors and Collaborators
The University of Hong Kong

Publications:
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Responsible Party: Lui Mei Sze, Doctor, Queen Mary Hospital, Hong Kong
ClinicalTrials.gov Identifier: NCT01921816     History of Changes
Other Study ID Numbers: UW 12-173
First Posted: August 13, 2013    Key Record Dates
Last Update Posted: December 3, 2014
Last Verified: December 2014

Additional relevant MeSH terms:
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Renal Insufficiency
Kidney Diseases
Urologic Diseases
Citric Acid
Sodium Citrate
Anticoagulants
Calcium Chelating Agents
Chelating Agents
Sequestering Agents
Molecular Mechanisms of Pharmacological Action