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

December 2, 2014 updated by: Lui Mei Sze, The University of Hong Kong
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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Anticipated)

35

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Hong Kong
      • Hong Kong, Hong Kong, 852
        • Adult Intensive Care unit, Queen Mary Hospital

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

18 years to 90 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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:

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: Supportive Care
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Other: 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 Names:
  • Prismocitrate 18/0 (replacement solution), Prism0cal (dialysate), Gambro

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
up to 4 days

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
up to 4days
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
up to 4 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

The University of Hong Kong

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

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

May 1, 2012

Primary Completion (Actual)

August 1, 2013

Study Registration Dates

First Submitted

July 31, 2013

First Submitted That Met QC Criteria

August 9, 2013

First Posted (Estimate)

August 13, 2013

Study Record Updates

Last Update Posted (Estimate)

December 3, 2014

Last Update Submitted That Met QC Criteria

December 2, 2014

Last Verified

December 1, 2014

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • UW 12-173

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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