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Clinical Evaluation of Use of Prismocitrate 18 in Patients Undergoing Acute Continuous Renal Replacement Therapy (CRRT)

Phase 3
Terminated
Conditions
Regional Citrate Anticoagulation (RCA)
Continuous Renal Replacement Therapy (CRRT)
Acute Kidney Injury
Interventions
Other: No Anticoagulation
Registration Number
NCT02860130
Lead Sponsor
Vantive Health LLC
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.

Detailed Description

Not available

Recruitment & Eligibility

Status
TERMINATED
Sex
All
Target Recruitment
34
Inclusion Criteria
  1. 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).
  2. Adult patients with AKI or other serious conditions who require treatment with CRRT.
  3. Patients are expected to remain in the ICU and on CRRT for at least 72 hours after randomization.
  4. Patients already receiving standard-of-care CRRT must be randomized within 24 hours of initiation of their standard-of-care CRRT.
Exclusion Criteria
  1. 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.
  2. 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).
  3. Patients who are not candidates for CRRT.
  4. Patients who are receiving extracorporeal membrane oxygenation (ECMO) therapy.
  5. 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.
  6. Patients with fulminant acute liver failure or acute on chronic liver failure as documented by a Child-Pugh Liver Failure Score > 10.
  7. 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.
  8. Patients unlikely to survive at least 72 hours.
  9. Female patients who are pregnant, lactating, or planning to become pregnant during the study period.
  10. Patients who are currently participating in another interventional clinical study.
  11. Patients with a medical condition that may interfere with the study objectives.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Prismocitrate 18Prismocitrate 18-
No Regional Anticoagulation of CRRT CircuitNo Anticoagulation-
Primary Outcome Measures
NameTimeMethod
Time to Occurrence of Selected Prismaflex® System Alarms/ConditionsUp to 120 hours post CRRT treatment initiation

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
NameTimeMethod
Number of Participants With Bleeding EventsUp to 120 hours post CRRT treatment initiation
Change From Baseline in Patient Ionized Calcium (iCa) by HourBaseline and up to 120 hours post CRRT treatment initiation

Systemic blood iCa concentrations

Number of Investigator Site Facilities That Passed Prismocitrate 18 Training AssessmentPrior to study use of Prismocitrate 18

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 HourBaseline and up to 120 hours post CRRT treatment initiation
Change From Baseline in Serum Chloride by HourBaseline and up to 120 hours post CRRT treatment initiation
Change From Baseline in Serum Potassium by HourBaseline and up to 120 hours post CRRT treatment initiation
Extracorporeal Circuit Ionized Calcium by HourUp to 120 hours post CRRT treatment initiation

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 DayUp to 120 hours post CRRT treatment initiation

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.

Change From Baseline in pH by HourBaseline and up to 120 hours post CRRT treatment initiation
Change From Baseline in Serum Sodium by HourBaseline and up to 120 hours post CRRT treatment initiation
Change From Baseline in Base Excess by HourBaseline and up to 120 hours post CRRT treatment initiation
Change From Baseline in Serum Phosphate by HourBaseline and up to 120 hours post CRRT treatment initiation
Number of Participants Reporting Any Baxter Device/Product Related Adverse Events (Serious and Non-Serious)Up to 30 days post study CRRT treatment completion
Change From Baseline in Respiratory Rate at Last VisitBaseline and up to 120 hours post CRRT treatment initiation
Change From Baseline in Blood Total Calcium Concentration by HourBaseline and up to 120 hours post CRRT treatment initiation
Change From Baseline in Pulse at Last VisitBaseline and up to 120 hours post CRRT treatment initiation
Change From Baseline in Serum Anion Gap by HourBaseline and up to 120 hours post CRRT treatment initiation
Change From Baseline in Serum Magnesium by HourBaseline and up to 120 hours post CRRT treatment initiation
Number of Participants by Number of Blood TransfusionsUp to 120 hours post CRRT treatment initiation
Change From Baseline in Blood Pressure at Last VisitBaseline and up to 120 hours post CRRT treatment initiation
Change From Baseline in Temperature at Last VisitBaseline and up to 120 hours post CRRT treatment initiation
Change From Baseline in Total Calcium/iCa Ratio by HourBaseline and up to 120 hours post CRRT treatment initiation
Duration of Bleeding EventsUp to 120 hours post CRRT treatment initiation
Number of Bleeding Events by LocationUp to 120 hours post CRRT treatment initiation

Trial Locations

Locations (12)

Emory University

🇺🇸

Atlanta, Georgia, United States

Northwestern University

🇺🇸

Chicago, Illinois, United States

University of Mississippi Medical Center

🇺🇸

Jackson, Mississippi, United States

University of Maryland Medical Center

🇺🇸

Baltimore, Maryland, United States

Beth Israel Deaconess (Harvard)

🇺🇸

Boston, Massachusetts, United States

Cleveland Clinic

🇺🇸

Cleveland, Ohio, United States

University of Alberta Hospital

🇨🇦

Edmonton, Alberta, Canada

Yale University School of Medicine

🇺🇸

New Haven, Connecticut, United States

University of Arizona

🇺🇸

Tucson, Arizona, United States

University of Kentucky

🇺🇸

Lexington, Kentucky, United States

University of Alabama at Birmingham

🇺🇸

Birmingham, Alabama, United States

University of Kansas Medical Center

🇺🇸

Kansas City, Kansas, United States

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