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

Acute Kidney Injury Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02860130
• Other study ID #: 1407-004
• Status: Terminated
• Phase: Phase 3
• Start date: September 27, 2016
• Est. completion date: May 12, 2018

Study information

• Verified date: December 2020
• Source: Baxter Healthcare Corporation
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 34
• Est. completion date: May 12, 2018
• Est. primary completion date: May 12, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

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

Intervention

Drug:
• Prismocitrate 18
Modality of CVVHDF

Other:
• No Anticoagulation
Modality of CVVHDF

Locations

Country	Name	City	State
Canada	University of Alberta Hospital	Edmonton	Alberta
United States	Emory University	Atlanta	Georgia
United States	University of Maryland Medical Center	Baltimore	Maryland
United States	University of Alabama at Birmingham	Birmingham	Alabama
United States	Beth Israel Deaconess (Harvard)	Boston	Massachusetts
United States	Northwestern University	Chicago	Illinois
United States	Cleveland Clinic	Cleveland	Ohio
United States	University of Mississippi Medical Center	Jackson	Mississippi
United States	University of Kansas Medical Center	Kansas City	Kansas
United States	University of Kentucky	Lexington	Kentucky
United States	Yale University School of Medicine	New Haven	Connecticut
United States	University of Arizona	Tucson	Arizona

Sponsors (1)

Lead Sponsor	Collaborator
Baxter Healthcare Corporation

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Change From Baseline in Patient Ionized Calcium (iCa) by Hour	Systemic blood iCa concentrations	Baseline and up to 120 hours post CRRT treatment initiation
Secondary	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
Secondary	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
Secondary	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
Secondary	Change From Baseline in Serum Bicarbonate by Hour		Baseline and up to 120 hours post CRRT treatment initiation
Secondary	Change From Baseline in pH by Hour		Baseline and up to 120 hours post CRRT treatment initiation
Secondary	Change From Baseline in Base Excess by Hour		Baseline and up to 120 hours post CRRT treatment initiation
Secondary	Change From Baseline in Blood Total Calcium Concentration by Hour		Baseline and up to 120 hours post CRRT treatment initiation
Secondary	Change From Baseline in Serum Sodium by Hour		Baseline and up to 120 hours post CRRT treatment initiation
Secondary	Change From Baseline in Serum Anion Gap by Hour		Baseline and up to 120 hours post CRRT treatment initiation
Secondary	Change From Baseline in Serum Magnesium by Hour		Baseline and up to 120 hours post CRRT treatment initiation
Secondary	Change From Baseline in Serum Phosphate by Hour		Baseline and up to 120 hours post CRRT treatment initiation
Secondary	Change From Baseline in Serum Potassium by Hour		Baseline and up to 120 hours post CRRT treatment initiation
Secondary	Change From Baseline in Serum Chloride by Hour		Baseline and up to 120 hours post CRRT treatment initiation
Secondary	Number of Participants With Bleeding Events		Up to 120 hours post CRRT treatment initiation
Secondary	Number of Participants by Number of Blood Transfusions		Up to 120 hours post CRRT treatment initiation
Secondary	Number of Participants Reporting Any Baxter Device/Product Related Adverse Events (Serious and Non-Serious)		Up to 30 days post study CRRT treatment completion
Secondary	Change From Baseline in Blood Pressure at Last Visit		Baseline and up to 120 hours post CRRT treatment initiation
Secondary	Change From Baseline in Respiratory Rate at Last Visit		Baseline and up to 120 hours post CRRT treatment initiation
Secondary	Change From Baseline in Temperature at Last Visit		Baseline and up to 120 hours post CRRT treatment initiation
Secondary	Change From Baseline in Pulse at Last Visit		Baseline and up to 120 hours post CRRT treatment initiation
Secondary	Change From Baseline in Total Calcium/iCa Ratio by Hour		Baseline and up to 120 hours post CRRT treatment initiation
Secondary	Number of Bleeding Events by Location		Up to 120 hours post CRRT treatment initiation
Secondary	Duration of Bleeding Events		Up to 120 hours post CRRT treatment initiation