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Evaluation of a Simplified Protocol for Regional Citrate Anticoagulation in Continuous Venovenous Hemodiafiltration

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 evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00583765
Recruitment Status : Completed
First Posted : December 31, 2007
Last Update Posted : June 4, 2008
Sponsor:
Collaborator:
Gambro Renal Products, Inc.
Information provided by:
University of Alberta

Tracking Information
First Submitted Date December 20, 2007
First Posted Date December 31, 2007
Last Update Posted Date June 4, 2008
Study Start Date April 2005
Actual Primary Completion Date March 2008   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures
 (submitted: December 20, 2007)
metabolic stability [ Time Frame: 24, 48 and 72 hours ]
Original Primary Outcome Measures Same as current
Change History
Current Secondary Outcome Measures
 (submitted: December 20, 2007)
Hemofilter survival [ Time Frame: 24, 48 and 72 hours ]
Original Secondary Outcome Measures Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title Evaluation of a Simplified Protocol for Regional Citrate Anticoagulation in Continuous Venovenous Hemodiafiltration
Official Title Evaluation of a Simplified Protocol for Regional Citrate Anticoagulation in Continuous Venovenous Hemodiafiltration
Brief Summary

Dialysis requires thinning of the blood to prevent clotting in the dialysis machine. Thinning of the blood is necessary but some forms of blood thinners may cause bleeding. Therefore, researchers are seeking ways to minimize bleeding risks and ensure effective dialysis.

One medication used to thin the blood in the dialysis machine is citrate. Citrate has the advantage of having its blood-thinning properties quickly reversed by calcium in the patient's blood. As a consequence, only the blood in the machine is thinned, greatly reducing the risk of bleeding when dialysis is carried out using other blood thinners. Until now, most patients who received citrate for dialysis were administered the citrate in a separate infusion through an IV pump into the dialysis machine. This method requires complex monitoring and calculations. This study is about Prismocitrate which is a dialysis fluid very similar to the regular dialysis fluid that is used in this intensive care unit, except that this fluid already contains exactly the correct amount of citrate. Thus, this method does not require a separate pump for citrate and calculations to pump the citrate into the blood as it goes through the kidney machine. Having the citrate already contained in the dialysis fluid simplifies the procedure and reduces the possibility of calculation errors.

This study seeks to determine if this simplified means of providing blood thinning in the kidney machine also results in the correct balance of blood salts.

Detailed Description

Acute renal failure is common among the critically ill [1-3] , and is an independent contributor to morbidity and mortality [4,5]. Continuous renal replacement therapy (CRRT) is commonly used for renal replacement in this group. This requires an extracorporeal circuit, the maintenance of which requires anticoagulation. Heparin has been the most common anticoagulant used with CRRT. However, heparin exposure for CRRT is major risk after surgery or trauma. Citrate has been used as a regional anticoagulant for plasmapheresis and chronic dialysis for many years [12,13], and is increasingly being used for CRRT. Regional anticoagulation refers to the provision of anticoagulation within the extracorporeal circuit without any alteration in coagulation in the patient's systemic circulation. Calcium is a co-factor in coagulation. Citrate reduces levels of ionized calcium in blood of the extracorporeal circuit to levels where coagulation cannot occur. Once the blood is returned to the patient's systemic circulation, the calcium levels are restored and coagulation can occur again. Renal replacement solutions for CRRT using citrate anticoagulation, should be calcium-free. [14-19] Despite a reduced risk of bleeding, widespread adoption of citrate regional anticoagulation has been limited by a lack of commercially available calcium-free solutions and the complexity of many protocols. Part of this complexity is the requirement for a separate citrate infusion into the extracorporeal circuit to achieve regional anticoagulation. This simplified protocol provides citrate in the replacement fluid infused prefilter as both anticoagulant and as buffer.

To predict appropriate replacement rates, Hospal Gambro scientific laboratories have developed a calculation model to predict the physiological interactions between the components of the administered replacement- and hemodialysis fluids and the patient's complex metabolic system. These interactions are influenced, in large part, by systemic parameters such as blood-flow and ultrafiltration rates, and patient parameters, such as acid base-status and liver function. This calculation model needs clinical validation in respect to its ability to predict the outcome and narrow the margin of metabolic disturbances caused by the administration of citrate anticoagulation. A previous study of a similar replacement fluid using citrate 8 mmol/L and citric acid 4 mmol/L resulted in mild metabolic acidosis of minimal clinical significance in some subjects and so this study will evaluate a modified version of fluid containing citrate 10 mmol/L and citric acid 2 mmol/L which has been calculated to provide optimal metabolic balance.

Subjects:

Twenty patients in the General Systems ICU at the University of Alberta Hospital treated with CVVHDF using a Prisma-CFM machine will be studied.

Inclusion criteria:

  1. Male or female between 17 and 80 years of age.
  2. Intensive care unit patient.
  3. Renal failure requiring CVVHDF.
  4. Likely to survive for at least 72 hours.

Exclusion criteria

  1. Age > 80 years
  2. Need for systemic anticoagulation, fibrinolytic therapy or activated protein C
  3. Acute or chronic hepatic failure

Patients are treated by regular CVVHDF setting in pre-dilution mode. The replacement flow-rate for the citrate replacement fluid depends on the blood pump speed [fixed ratio, see 9.3 and table below]. Mean dialysate flow is between 100 ml/hr and 2500ml/hour in accordance to the desired base-equivalent intake. Access pressure is kept between -100 and 150mmHg. Access and return pressure are monitored. Specially formulated replacement- and dialysate fluids are used.

Citrate anticoagulation Published literature data show that a mean citrate-dosage of 3.5 to 4mmol/l of undiluted blood is necessary to decrease the level of ionized serum calcium below 0.4mmol/l which provides sufficient anticoagulation to maintain an extracorporeal circuit. A minimum citrate concentration of 3.5 mmol/l blood will be used in this protocol. The infused citrate replacement fluid contains trisodium citrate and citric acid in a mixture (10mmol/l tri-sodium citrate plus 2 mmol/l citric acid). Preliminary results proved that the anticoagulation potency of this mixture is similar to a plain 12 mmol/l tri-sodium citrate solution. Therefore a fixed ratio of citrate replacement fluid will be infused in pre-pump predilution mode per 1 liter of effective blood flow.

Calcium replacement:

The loss of calcium- and magnesium-citrate in the ultra-filtrate via the hemofilter needs to be compensated to avoid systemic hypocalcemia and hypomagnesemia. Calcium replacement solution is prepared by removing 300 mls from a 1000 mls bag of 0.9% saline and subsequently adding 200 mls of 10% calcium gluconate to this bag. This calcium gluconate solution is infused via a central line at an initial infusion rate of 60 ml/hr. Ionized calcium levels are monitored every 6-8 hours and corrected by changing of flow rate of the infusion.

Potassium replacement:

Potassium is added into the replacement and dialysate fluid based on clinical requirement.

Sodium-bicarbonate adjustment:

The sodium bicarbonate level is influenced by the flow-rate of the replacement fluid (citrate intake) and the dialysate flow (bicarbonate intake). It is monitored every 6 hours and is corrected during treatment by altering the dialysate flow. Reducing the flow rate lowers bicarbonate intake in case of metabolic alkalosis, raising flow increases the bicarbonate intake in case of metabolic acidosis. If these adjustments are not successful, further corrections can be done by adding bicarbonate into the next dialysate fluid bag, when it is changed:

Consent procedure Subjects will be identified, recruited and informed consent obtained by the principal investigator, co-investigator or research co-ordinators.

Study benefits The study renal replacement solution includes all elements required for safe use. It does not require custom preparation by hospital personnel. This will minimize risk of error and increase patient safety. It is hoped this study will eventually enable the general use of a simple safe technique for citrate regional anticoagulation during continuous renal replacement therapy.

Adverse effects CVVHDF using citrate regional anticoagulation using any protocol may be associated with hypocalcemia, metabolic alkalosis or acidosis, hypernatremia or hyponatremia. In anticipation of this, all protocols including this one use extensive metabolic monitoring and algorithmic responses to abnormalities. This simplified protocol minimizes the potential for complication.

Adverse effects would be notified to patient or family, investigator, and HREB committee.

Privacy Patient data will be anonymized to prevent identification. Gambro Canada (study sponsor) will have access to anonymized case report forms and aggregate report.

Study Type Observational
Study Design Observational Model: Cohort
Time Perspective: Prospective
Target Follow-Up Duration Not Provided
Biospecimen Not Provided
Sampling Method Non-Probability Sample
Study Population
  1. Male or female between 17 and 80 years of age.
  2. Critically ill intensive care unit patient.
  3. Renal failure requiring continuous venovenous hemodiafiltration.
  4. Likely to survive for at least 72 hours
Condition Kidney Failure, Acute
Intervention Drug: Regional citrate anticoagulation
Continuous venovenous hemodiafiltration with regional anticoagulation using dilute trisodium citrate. This requires the use of a continuous renal replacement therapy (CRRT) machine in venovenous hemodiafiltration mode. Anticoagulation and buffer are provided by the use of a dilute solution of trisodium citrate in the replacement fluid which is infused in a predilution mode. Standard bicarbonate containing dialysate is used.
Other Names:
  • Prismocitrate - the study fluid
  • Prismocal - the commercially available dialysate
Study Groups/Cohorts A
Critically ill patients with acute renal failure requiring continuous renal replacement therapy
Intervention: Drug: Regional citrate anticoagulation
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status Completed
Actual Enrollment
 (submitted: December 20, 2007)
20
Original Estimated Enrollment Same as current
Actual Study Completion Date March 2008
Actual Primary Completion Date March 2008   (Final data collection date for primary outcome measure)
Eligibility Criteria

Inclusion Criteria:

  • Male or female between 17 and 80 years of age.
  • Intensive care unit patient.
  • Acute renal failure requiring continuous venovenous hemodiafiltration.
  • Likely to survive for at least 72 hours

Exclusion Criteria:

  • Age > 80 years
  • Need for systemic anticoagulation, fibrinolytic therapy or activated protein C
  • Acute or chronic hepatic failure
Sex/Gender
Sexes Eligible for Study: All
Ages 17 Years to 80 Years   (Child, Adult, Older Adult)
Accepts Healthy Volunteers No
Contacts Contact information is only displayed when the study is recruiting subjects
Listed Location Countries Canada
Removed Location Countries  
 
Administrative Information
NCT Number NCT00583765
Other Study ID Numbers 5793
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement Not Provided
Responsible Party R.T.Noel Gibney, Division of Critical Care Medicine, University of Alberta
Study Sponsor University of Alberta
Collaborators Gambro Renal Products, Inc.
Investigators
Principal Investigator: Noel Gibney, MB BCh BAO University of Alberta
PRS Account University of Alberta
Verification Date June 2008