Safety Evaluation of Prismocitrate 18 in Patients Receiving CRRT

Acute Kidney Injury (AKI) Clinical Trial

Official title:

A Safety Evaluation of Prismocitrate 18 in Patients Receiving Continuous Renal Replacement Therapy (CRRT)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05399537
• Other study ID #: BXU558476
• Status: Recruiting
• Phase: Phase 3
• Start date: April 1, 2024
• Est. completion date: September 26, 2025

Study information

• Verified date: June 2024
• Source: Baxter Healthcare Corporation
• Contact: Baxter Clinical Trials Disclosure Call Center
• Phone: (224) 948-7359
• Email: trials[@]Baxter.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Prismocitrate 18 is a continuous renal replacement therapy (CRRT) solution to be used as a renal replacement solution and as an anticoagulant to prevent blood clotting in the extracorporeal circuit.

The objectives of this study are: 1) to confirm the safety of Prismocitrate 18 in patients receiving CRRT using continuous venovenous hemodiafiltration (CVVHDF) or continuous venovenous hemofiltration (CVVH) and 2) to observe that the PrisMax System allows for implementation of regional citrate anticoagulation (RCA) (citrate and calcium dosing) during CRRT with Prismocitrate 18 and intended prescription. The study period of the patient's CRRT will be up to 10 days.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 40
• Est. completion date: September 26, 2025
• Est. primary completion date: September 26, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Patients must be >=18 years of age

• Patients who are candidates for CRRT

• Patients expected to survive for at least 24 hours

• Patients with a contraindication to heparin or an increased risk of hemorrhage

• Patient and/or legally-authorized representative has signed a written informed consent form (ICF) per 21 CFR Part 50.55(e)

Exclusion Criteria:

• Patients with a known allergy to citrate or who have ever experienced an adverse reaction associated with citrate products, including patients with a prior history of citrate toxicity

• Patients with acute liver failure, defined by the occurrence of encephalopathy and hepatic synthetic dysfunction within 26 weeks of the first symptoms of liver disease and without evidence of chronic liver disease

• Patients with acute-on-chronic liver failure characterized by acute decompensation of cirrhosis and a Child-Pugh Liver Failure Score > 10

• Patients with refractory shock and associated lactic acidosis (lactate > 4 mmol/L)

• Patients with a systemic ionized calcium concentration outside the normal physiologic range (1.0 - 1.3 mmol/L), or outside of the laboratory reference range (Note: It is acceptable to provide calcium supplementation or treatment for hypercalcemia to achieve a normal physiologic range prior to therapy initiation)

• Female patients of childbearing potential who are pregnant or breastfeeding. (Note:

All female patients, who have not undergone a hysterectomy, bilateral oophorectomy with or without hysterectomy, or has medically documented ovarian failure before study Screening must have a negative serum beta human chorionic gonadotropic [B-hCG] pregnancy test at Screening)

• Patients who are currently participating in another interventional clinical study

Related Conditions & MeSH terms

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

Intervention

Drug:
• Prismocitrate 18
Prismocitrate 18 solution will be used in pre-dilution mode only; the rate of administration depends on the targeted citrate dose and the prescribed flow rate. The pre-filter infusion rate of Prismocitrate 18 solution will be indexed to the blood flow rate (BFR) to achieve a target blood citrate concentration of 3 mmol/L of blood. A BFR between 100 - 180 mL/min will be advised; a lower BFR can minimize patient citrate exposure, particularly in patients with lower body weight.

Locations

Country	Name	City	State
United States	Southeast Renal Research Institute	Chattanooga	Tennessee
United States	Methodist Dallas Medical Center	Dallas	Texas
United States	University of California Los Angeles	Los Angeles	California
United States	University of Southern California (USC) / Keck Hospital	Los Angeles	California
United States	Gamma Medical Research, Inc / McAllen Medical Center	McAllen	Texas
United States	Lt. Col. Luke Weathers, Jr. VA Medical Center	Memphis	Tennessee
United States	Rutgers-New Jersey Medical School/ University Hospital	Newark	New Jersey
United States	VA Pittsburgh Healthcare System	Pittsburgh	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
Baxter Healthcare Corporation

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of participants with symptomatic hypocalcemia	Defined as symptomatic patients (e.g., tetany/spasms, seizures, or cardiac events secondary to a prolonged QT interval), with symptoms deemed attributable to hypocalcemia and with a confirmed systemic ionized calcium < 0.9 mmol/L.	Day 1 up to Day 10
Primary	Number of participants with symptomatic hypercalcemia	Defined as symptomatic patients (e.g., changes in mental status not explained by the interventions or underlying conditions or cardiac events secondary to a shortened QT interval), with symptoms deemed attributable to hypercalcemia and with a confirmed systemic ionized calcium > 1.4 mmol/L.	Day 1 up to Day 10
Primary	Number of participants with symptomatic citrate accumulation	Defined as symptomatic patients (e.g., refractory acidosis), with symptoms deemed attributable to citrate accumulation and with a systemic total calcium to ionized calcium ratio > 2.5.	Day 1 up to Day 10
Secondary	Number of participants with Adverse Events related to study product and/or procedure	Incidence of AE and SAE's are also considered secondary outcome measures and will be reported in the Adverse Event section	Day 1 up to Day 28
Secondary	Lab measurement for Systemic Ionized Calcium by Time Point		Baseline (<=6 hours prior to Day 1 initiation of CRRT); Day 1 (1 hour after initiation of CRRT, 1 hour after any Prismocitrate dose change until stable) and every 6 hours (i.e., 6, 12, 18, 24) up to Day 10
Secondary	Lab measurement for pH by Time Point		Baseline (<=6 hours prior to Day 1 initiation of CRRT); Day 1 (1 hour after initiation of CRRT, 1 hour after any Prismocitrate dose change until stable) and every 6 hours (i.e., 6, 12, 18, 24) up to Day 10
Secondary	Lab measurement for Base Excess by Time Point		Baseline (<=6 hours prior to Day 1 initiation of CRRT); Day 1 (1 hour after initiation of CRRT, 1 hour after any Prismocitrate dose change until stable) and every 6 hours (i.e., 6, 12, 18, 24) up to Day 10
Secondary	Lab measurement for Serum Bicarbonate by Time Point		Baseline (<=6 hours prior to Day 1 initiation of CRRT); Day 1 (1 hour after initiation of CRRT, 1 hour after any Prismocitrate dose change until stable) and every 6 hours (i.e., 6, 12, 18, 24) up to Day 10
Secondary	Lab measurement for Serum Magnesium by Time Point		Baseline (<=6 hours prior to Day 1 initiation of CRRT); Day 1 every 6 hours after initiation of CRRT (i.e., 6, 12, 18, 24) up to Day 10
Secondary	Lab measurement for Serum Potassium by Time Point		Baseline (<=6 hours prior to Day 1 initiation of CRRT); Day 1 every 6 hours after initiation of CRRT (i.e., 6, 12, 18, 24) up to Day 10
Secondary	Lab measurement for Phosphate by Time Point		Baseline (<=6 hours prior to Day 1 initiation of CRRT); Day 1 every 12 hours after initiation of CRRT up to Day 10
Secondary	Lab measurement for Systemic Total Calcium Level by Time Point		Baseline (<=6 hours prior to Day 1 initiation of CRRT); Day 1 every 12 hours after initiation of CRRT up to Day 10
Secondary	Lab measurement for Total to Ionized Calcium Ratio by Time Point		Baseline (<=6 hours prior to Day 1 initiation of CRRT); Day 1 every 12 hours after initiation of CRRT up to Day 10
Secondary	Extracorporeal Circuit Life		Day 1 to Day 10
Secondary	Lab measurement for Post-filter Ionized Calcium Levels by Time Point		Baseline (<=6 hours prior to Day 1 initiation of CRRT); Day 1 (1 hour after initiation of CRRT, 1 hour after any Prismocitrate dose change until stable) and every 6 hours (i.e., 6h, 12h, 18h, 24h) up to Day 10
Secondary	Number of Adverse Events leading to withdrawal	Incidence of AE and SAE's are also considered secondary outcome measures and will be reported in the Adverse Event section	Day 1 up to Day 28