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

Study Overview
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Brief Summary
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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.

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

Conditions
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Regional Citrate Anticoagulation (RCA), Continuous Renal Replacement Therapy (CRRT), Acute Kidney Injury

Intervention / Treatment
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* Drug: Prismocitrate 18
* Other: No Anticoagulation


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Prismocitrate 18<br> | Drug: Prismocitrate 18<br>* Modality of CVVHDF<br>* Other names: Regional Citrate Anticoagulation (RCA);|
| Active Comparator: No Regional Anticoagulation of CRRT Circuit<br> | Other: No Anticoagulation<br>* Modality of CVVHDF<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Up to 120 hours post CRRT treatment initiation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Patient Ionized Calcium (iCa) by Hour | Systemic blood iCa concentrations | Baseline and up to 120 hours post CRRT treatment initiation | 
| 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). | Up to 120 hours post CRRT treatment initiation | 
| 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. | Up to 120 hours post CRRT treatment initiation | 
| 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. | Prior to study use of Prismocitrate 18 | 
| Change From Baseline in Serum Bicarbonate by Hour |  | Baseline and up to 120 hours post CRRT treatment initiation | 
| Change From Baseline in pH by Hour |  | Baseline and up to 120 hours post CRRT treatment initiation | 
| Change From Baseline in Base Excess by Hour |  | Baseline and up to 120 hours post CRRT treatment initiation | 
| Change From Baseline in Blood Total Calcium Concentration by Hour |  | Baseline and up to 120 hours post CRRT treatment initiation | 
| Change From Baseline in Serum Sodium by Hour |  | Baseline and up to 120 hours post CRRT treatment initiation | 
| Change From Baseline in Serum Anion Gap by Hour |  | Baseline and up to 120 hours post CRRT treatment initiation | 
| Change From Baseline in Serum Magnesium by Hour |  | Baseline and up to 120 hours post CRRT treatment initiation | 
| Change From Baseline in Serum Phosphate by Hour |  | Baseline and up to 120 hours post CRRT treatment initiation | 
| Change From Baseline in Serum Potassium by Hour |  | Baseline and up to 120 hours post CRRT treatment initiation | 
| Change From Baseline in Serum Chloride by Hour |  | Baseline and up to 120 hours post CRRT treatment initiation | 
| Number of Participants With Bleeding Events |  | Up to 120 hours post CRRT treatment initiation | 
| Number of Participants by Number of Blood Transfusions |  | 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 Blood Pressure at Last Visit |  | Baseline and up to 120 hours post CRRT treatment initiation | 
| Change From Baseline in Respiratory Rate at Last Visit |  | Baseline and up to 120 hours post CRRT treatment initiation | 
| Change From Baseline in Temperature at Last Visit |  | Baseline and up to 120 hours post CRRT treatment initiation | 
| Change From Baseline in Pulse at Last Visit |  | Baseline and up to 120 hours post CRRT treatment initiation | 
| Change From Baseline in Total Calcium/iCa Ratio by Hour |  | Baseline and up to 120 hours post CRRT treatment initiation | 
| Number of Bleeding Events by Location |  | Up to 120 hours post CRRT treatment initiation | 
| Duration of Bleeding Events |  | Up to 120 hours post CRRT treatment initiation | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Regional Citrate Anticoagulation (RCA), Continuous Renal Replacement Therapy (CRRT), Acute Kidney Injury