Back to resultsClinical Evaluation of Use of Prismocitrate 18 in Patients Undergoing Acute Continuous Renal Replacement Therapy (CRRT)
Primary Purpose
Regional Citrate Anticoagulation (RCA), Continuous Renal Replacement Therapy (CRRT), Acute Kidney Injury
Status
Terminated
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Prismocitrate 18
No Anticoagulation
Sponsored by
About this trial
This is an interventional treatment trial for Regional Citrate Anticoagulation (RCA) focused on measuring Regional Citrate Anticoagulation (RCA), Continuous Renal Replacement Therapy (CRRT), Acute Kidney Injury
Eligibility Criteria
Inclusion Criteria:
- Patient must be receiving medical care in an intensive care unit (ICU) (e.g., medical ICU, surgical ICU, cardiothoracic ICU, Trauma ICU, Mixed ICU, other).
- Adult patients with AKI or other serious conditions who require treatment with CRRT.
- Patients are expected to remain in the ICU and on CRRT for at least 72 hours after randomization.
- Patients already receiving standard-of-care CRRT must be randomized within 24 hours of initiation of their standard-of-care CRRT.
Exclusion Criteria:
- Patients requiring systemic anticoagulation with antithrombotic agents for reasons other than CRRT. The exception is patients receiving subcutaneous heparin for deep vein thrombosis prophylaxis according to institutional practice or patients on aspirin may be enrolled.
- Patients in whom citrate anticoagulation is contraindicated such as patients with a known allergy to citrate or who have experienced adverse events associated with citrate products including patients with a prior history of citrate toxicity or patients with uncorrected severe hypocalcemia (whether in the context of current citrate administration or due to the underlying disease state).
- Patients who are not candidates for CRRT.
- Patients who are receiving extracorporeal membrane oxygenation (ECMO) therapy.
- Patients with severe coagulopathy [i.e., platelets < 30,000/mm3, international normalized ratio (INR) > 2, partial thromboplastin time (PTT) > 50 seconds] including severe thrombocytopenia (platelets < 30,000/mm3), HIT (heparin induced thrombocytopenia), ITP (idiopathic thrombocytopenia purpura), and TTP (thrombotic thrombocytopenia purpura) should not be enrolled in the trial.
- Patients with fulminant acute liver failure or acute on chronic liver failure as documented by a Child-Pugh Liver Failure Score > 10.
- Patients with refractory shock associated persistent, worsening with lactic acidosis (lactate > 4 mmol/L). However, patients with improving subsequent serum lactate levels may be enrolled.
- Patients unlikely to survive at least 72 hours.
- Female patients who are pregnant, lactating, or planning to become pregnant during the study period.
- Patients who are currently participating in another interventional clinical study.
- Patients with a medical condition that may interfere with the study objectives.
Sites / Locations
- University of Alabama at Birmingham
- University of Arizona
- Yale University School of Medicine
- Emory University
- Northwestern University
- University of Kansas Medical Center
- University of Kentucky
- University of Maryland Medical Center
- Beth Israel Deaconess (Harvard)
- University of Mississippi Medical Center
- Cleveland Clinic
- University of Alberta Hospital
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
Prismocitrate 18
No Regional Anticoagulation of CRRT Circuit
Arm Description
Outcomes
Primary Outcome Measures
Time to Occurrence of Selected Prismaflex® System Alarms/Conditions
The point estimate is time point (number of hours of the extracorporeal circuit life of a filter) at which (100-percentile)% filters are still surviving (i.e. number surviving divided by number at risk), based on the Kaplan-Meier method. For example, for the 25th percentile: after 33.18 hours, 75% of filters are still surviving. Given the early termination, this study was not powered to show statistically significant changes in efficacy endpoints. The Prismaflex M150 Set extracorporeal circuit life of filters were intended to be assessed over a maximum of 120 hours (Treatment Period) by duration of time for which each Prismaflex M150 Set could be used continuously over a maximum 72 hour time-period in each patient. The end of the extracorporeal circuit life was defined by the occurrence of one or both of the following Prismaflex® System alarms/conditions if the alarms could not be mitigated: (1) "Warning: Filter Clotted", and/or (2) "Advisory transmembrane pressure (TMP) Too High."
Secondary Outcome Measures
Change From Baseline in Patient Ionized Calcium (iCa) by Hour
Systemic blood iCa concentrations
Extracorporeal Circuit Ionized Calcium by Hour
Post-filter blood iCa concentrations will only be measured in the Prismocitrate 18 arm. The extracorporeal circuit (post-filter).
Delivery of Prescribed CRRT Dose by Day
Evaluates the efficacy of using Prismocitrate 18 in delivering the prescribed CRRT dose, with delivered dose based on (daily) average effluent rate divided by (daily) average weight and expressed as mL/kg/hour.
Number of Investigator Site Facilities That Passed Prismocitrate 18 Training Assessment
Training conducted on administration of Prismocitrate 18 to demonstrate the understanding of the user groups on how to use the solution by passing an assessment at the end of training. The user groups who needed to be assessed prior to use of Prismocitrate 18 in the clinical trial setting were to be comprised of physicians, nurses, and other clinicians who were part of prescribing, initiating or modifying treatment during the 120 hour Treatment Period. The training assessment was housed on a restricted access study website. Study personnel who completed the training assessment have a completion date listed which indicates that the individual received a passing score of 80% or better on the training assessment.
Change From Baseline in Serum Bicarbonate by Hour
Change From Baseline in pH by Hour
Change From Baseline in Base Excess by Hour
Change From Baseline in Blood Total Calcium Concentration by Hour
Change From Baseline in Serum Sodium by Hour
Change From Baseline in Serum Anion Gap by Hour
Change From Baseline in Serum Magnesium by Hour
Change From Baseline in Serum Phosphate by Hour
Change From Baseline in Serum Potassium by Hour
Change From Baseline in Serum Chloride by Hour
Number of Participants With Bleeding Events
Number of Participants by Number of Blood Transfusions
Number of Participants Reporting Any Baxter Device/Product Related Adverse Events (Serious and Non-Serious)
Change From Baseline in Blood Pressure at Last Visit
Change From Baseline in Respiratory Rate at Last Visit
Change From Baseline in Temperature at Last Visit
Change From Baseline in Pulse at Last Visit
Change From Baseline in Total Calcium/iCa Ratio by Hour
Number of Bleeding Events by Location
Duration of Bleeding Events
Full Information
NCT ID
NCT02860130
First Posted
July 29, 2016
Last Updated
December 9, 2020
Sponsor
Baxter Healthcare Corporation
1. Study Identification
Unique Protocol Identification Number
NCT02860130
Brief Title
Clinical Evaluation of Use of Prismocitrate 18 in Patients Undergoing Acute Continuous Renal Replacement Therapy (CRRT)
Official Title
Clinical Evaluation of Use of Prismocitrate 18 in Patients Undergoing Acute Continuous Renal Replacement Therapy (CRRT)
Study Type
Interventional
2. Study Status
Record Verification Date
December 2020
Overall Recruitment Status
Terminated
Why Stopped
Study halted due to low recruitment, unrelated to safety or efficacy reasons
Study Start Date
September 27, 2016 (Actual)
Primary Completion Date
May 12, 2018 (Actual)
Study Completion Date
May 12, 2018 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Baxter Healthcare Corporation
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The purpose of this research is to determine if an investigational new drug solution called Prismocitrate 18 lengthens extracorporeal circuit life in patients treated with continuous renal replacement therapy (CRRT). Patients who receive CRRT treatment with Prismocitrate 18 as the anticoagulant will be compared to patients who receive CRRT treatment with no anticoagulation.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Regional Citrate Anticoagulation (RCA), Continuous Renal Replacement Therapy (CRRT), Acute Kidney Injury
Keywords
Regional Citrate Anticoagulation (RCA), Continuous Renal Replacement Therapy (CRRT), Acute Kidney Injury
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
34 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Prismocitrate 18
Arm Type
Experimental
Arm Title
No Regional Anticoagulation of CRRT Circuit
Arm Type
Active Comparator
Intervention Type
Drug
Intervention Name(s)
Prismocitrate 18
Other Intervention Name(s)
Regional Citrate Anticoagulation (RCA)
Intervention Description
Modality of CVVHDF
Intervention Type
Other
Intervention Name(s)
No Anticoagulation
Intervention Description
Modality of CVVHDF
Primary Outcome Measure Information:
Title
Time to Occurrence of Selected Prismaflex® System Alarms/Conditions
Description
The point estimate is time point (number of hours of the extracorporeal circuit life of a filter) at which (100-percentile)% filters are still surviving (i.e. number surviving divided by number at risk), based on the Kaplan-Meier method. For example, for the 25th percentile: after 33.18 hours, 75% of filters are still surviving. Given the early termination, this study was not powered to show statistically significant changes in efficacy endpoints. The Prismaflex M150 Set extracorporeal circuit life of filters were intended to be assessed over a maximum of 120 hours (Treatment Period) by duration of time for which each Prismaflex M150 Set could be used continuously over a maximum 72 hour time-period in each patient. The end of the extracorporeal circuit life was defined by the occurrence of one or both of the following Prismaflex® System alarms/conditions if the alarms could not be mitigated: (1) "Warning: Filter Clotted", and/or (2) "Advisory transmembrane pressure (TMP) Too High."
Time Frame
Up to 120 hours post CRRT treatment initiation
Secondary Outcome Measure Information:
Title
Change From Baseline in Patient Ionized Calcium (iCa) by Hour
Description
Systemic blood iCa concentrations
Time Frame
Baseline and up to 120 hours post CRRT treatment initiation
Title
Extracorporeal Circuit Ionized Calcium by Hour
Description
Post-filter blood iCa concentrations will only be measured in the Prismocitrate 18 arm. The extracorporeal circuit (post-filter).
Time Frame
Up to 120 hours post CRRT treatment initiation
Title
Delivery of Prescribed CRRT Dose by Day
Description
Evaluates the efficacy of using Prismocitrate 18 in delivering the prescribed CRRT dose, with delivered dose based on (daily) average effluent rate divided by (daily) average weight and expressed as mL/kg/hour.
Time Frame
Up to 120 hours post CRRT treatment initiation
Title
Number of Investigator Site Facilities That Passed Prismocitrate 18 Training Assessment
Description
Training conducted on administration of Prismocitrate 18 to demonstrate the understanding of the user groups on how to use the solution by passing an assessment at the end of training. The user groups who needed to be assessed prior to use of Prismocitrate 18 in the clinical trial setting were to be comprised of physicians, nurses, and other clinicians who were part of prescribing, initiating or modifying treatment during the 120 hour Treatment Period. The training assessment was housed on a restricted access study website. Study personnel who completed the training assessment have a completion date listed which indicates that the individual received a passing score of 80% or better on the training assessment.
Time Frame
Prior to study use of Prismocitrate 18
Title
Change From Baseline in Serum Bicarbonate by Hour
Time Frame
Baseline and up to 120 hours post CRRT treatment initiation
Title
Change From Baseline in pH by Hour
Time Frame
Baseline and up to 120 hours post CRRT treatment initiation
Title
Change From Baseline in Base Excess by Hour
Time Frame
Baseline and up to 120 hours post CRRT treatment initiation
Title
Change From Baseline in Blood Total Calcium Concentration by Hour
Time Frame
Baseline and up to 120 hours post CRRT treatment initiation
Title
Change From Baseline in Serum Sodium by Hour
Time Frame
Baseline and up to 120 hours post CRRT treatment initiation
Title
Change From Baseline in Serum Anion Gap by Hour
Time Frame
Baseline and up to 120 hours post CRRT treatment initiation
Title
Change From Baseline in Serum Magnesium by Hour
Time Frame
Baseline and up to 120 hours post CRRT treatment initiation
Title
Change From Baseline in Serum Phosphate by Hour
Time Frame
Baseline and up to 120 hours post CRRT treatment initiation
Title
Change From Baseline in Serum Potassium by Hour
Time Frame
Baseline and up to 120 hours post CRRT treatment initiation
Title
Change From Baseline in Serum Chloride by Hour
Time Frame
Baseline and up to 120 hours post CRRT treatment initiation
Title
Number of Participants With Bleeding Events
Time Frame
Up to 120 hours post CRRT treatment initiation
Title
Number of Participants by Number of Blood Transfusions
Time Frame
Up to 120 hours post CRRT treatment initiation
Title
Number of Participants Reporting Any Baxter Device/Product Related Adverse Events (Serious and Non-Serious)
Time Frame
Up to 30 days post study CRRT treatment completion
Title
Change From Baseline in Blood Pressure at Last Visit
Time Frame
Baseline and up to 120 hours post CRRT treatment initiation
Title
Change From Baseline in Respiratory Rate at Last Visit
Time Frame
Baseline and up to 120 hours post CRRT treatment initiation
Title
Change From Baseline in Temperature at Last Visit
Time Frame
Baseline and up to 120 hours post CRRT treatment initiation
Title
Change From Baseline in Pulse at Last Visit
Time Frame
Baseline and up to 120 hours post CRRT treatment initiation
Title
Change From Baseline in Total Calcium/iCa Ratio by Hour
Time Frame
Baseline and up to 120 hours post CRRT treatment initiation
Title
Number of Bleeding Events by Location
Time Frame
Up to 120 hours post CRRT treatment initiation
Title
Duration of Bleeding Events
Time Frame
Up to 120 hours post CRRT treatment initiation
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Patient must be receiving medical care in an intensive care unit (ICU) (e.g., medical ICU, surgical ICU, cardiothoracic ICU, Trauma ICU, Mixed ICU, other).
Adult patients with AKI or other serious conditions who require treatment with CRRT.
Patients are expected to remain in the ICU and on CRRT for at least 72 hours after randomization.
Patients already receiving standard-of-care CRRT must be randomized within 24 hours of initiation of their standard-of-care CRRT.
Exclusion Criteria:
Patients requiring systemic anticoagulation with antithrombotic agents for reasons other than CRRT. The exception is patients receiving subcutaneous heparin for deep vein thrombosis prophylaxis according to institutional practice or patients on aspirin may be enrolled.
Patients in whom citrate anticoagulation is contraindicated such as patients with a known allergy to citrate or who have experienced adverse events associated with citrate products including patients with a prior history of citrate toxicity or patients with uncorrected severe hypocalcemia (whether in the context of current citrate administration or due to the underlying disease state).
Patients who are not candidates for CRRT.
Patients who are receiving extracorporeal membrane oxygenation (ECMO) therapy.
Patients with severe coagulopathy [i.e., platelets < 30,000/mm3, international normalized ratio (INR) > 2, partial thromboplastin time (PTT) > 50 seconds] including severe thrombocytopenia (platelets < 30,000/mm3), HIT (heparin induced thrombocytopenia), ITP (idiopathic thrombocytopenia purpura), and TTP (thrombotic thrombocytopenia purpura) should not be enrolled in the trial.
Patients with fulminant acute liver failure or acute on chronic liver failure as documented by a Child-Pugh Liver Failure Score > 10.
Patients with refractory shock associated persistent, worsening with lactic acidosis (lactate > 4 mmol/L). However, patients with improving subsequent serum lactate levels may be enrolled.
Patients unlikely to survive at least 72 hours.
Female patients who are pregnant, lactating, or planning to become pregnant during the study period.
Patients who are currently participating in another interventional clinical study.
Patients with a medical condition that may interfere with the study objectives.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Qing Li, MD
Organizational Affiliation
Baxter Healthcare Corporation
Official's Role
Study Director
Facility Information:
Facility Name
University of Alabama at Birmingham
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35294
Country
United States
Facility Name
University of Arizona
City
Tucson
State/Province
Arizona
ZIP/Postal Code
85724
Country
United States
Facility Name
Yale University School of Medicine
City
New Haven
State/Province
Connecticut
ZIP/Postal Code
06520
Country
United States
Facility Name
Emory University
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30322
Country
United States
Facility Name
Northwestern University
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60611
Country
United States
Facility Name
University of Kansas Medical Center
City
Kansas City
State/Province
Kansas
ZIP/Postal Code
66160
Country
United States
Facility Name
University of Kentucky
City
Lexington
State/Province
Kentucky
ZIP/Postal Code
40526
Country
United States
Facility Name
University of Maryland Medical Center
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21201
Country
United States
Facility Name
Beth Israel Deaconess (Harvard)
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States
Facility Name
University of Mississippi Medical Center
City
Jackson
State/Province
Mississippi
ZIP/Postal Code
39216
Country
United States
Facility Name
Cleveland Clinic
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44195
Country
United States
Facility Name
University of Alberta Hospital
City
Edmonton
State/Province
Alberta
ZIP/Postal Code
T6G2B7
Country
Canada
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
33314078
Citation
Tsujimoto H, Tsujimoto Y, Nakata Y, Fujii T, Takahashi S, Akazawa M, Kataoka Y. Pharmacological interventions for preventing clotting of extracorporeal circuits during continuous renal replacement therapy. Cochrane Database Syst Rev. 2020 Dec 14;12(12):CD012467. doi: 10.1002/14651858.CD012467.pub3.
Results Reference
derived
Learn more about this trial
Clinical Evaluation of Use of Prismocitrate 18 in Patients Undergoing Acute Continuous Renal Replacement Therapy (CRRT)
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