Continuous Renal Replacement Therapy for Acute Kidney Injury by Cooling Blood

Improving Outcomes in Patients Receiving Continuous Renal Replacement Therapy for Acute Kidney Injury by Cooling Blood in the Dialysis Circuit (CRRiTiCool): a Randomized Controlled Trial

Acute kidney injury (AKI) is common in intensive care unit (ICU) patients and is associated with longer hospital stays and worse survival. The mortality rate of critically ill patients in the ICU who receive renal replacement therapy for AKI ranges between 50-80%, cardiovascular disease being the second largest cause of death. A previous pilot study from the investigator's group showed that myocardial stunning occurs in AKI patients during continuous renal replacement therapy (CRRT) and may explain the high cardiovascular mortality in this population. In the chronic intermittent dialysis setting, mild dialysate cooling was shown to improve intradialytic hemodynamic stability and prevent myocardial stunning. The aim of this study is to find out whether cooling the blood in the CRRT circuit is an effective intervention to prevent myocardial stunning in AKI patients undergoing CRRT and improve patient outcomes.

Study Overview

• Status: Withdrawn
• Conditions: Acute Kidney Injury; Continuous Renal Replacement Therapy
• Intervention / Treatment: Procedure: Dialysis cooling

Detailed Description

This is a single center, prospective, randomized, open label, controlled trial comparing standard-of-care temperature management with blood cooling CRRT. We will recruit approximately 140 patients (70 in each group) from the Medical Surgical Intensive Care Unit at University Hospital and The Critical Care Trauma Center at Victoria Hospital in London, Ontario.

The study team will randomize patients with acute kidney injury requiring continuous dialysis therapy into one of two groups; either to standard of care continuous dialysis therapy or to cool blood continuous dialysis therapy. All therapy will be delivered using the Baxter PrisMaxTM CRRT machine with TherMaxTM blood warmer.

All participants will undergo a series of echocardiograms (ultrasound of your heart) prior to continuous dialysis therapy initiation, 4-12 hours into therapy, for up to 7 days after therapy initiation, and at discharge from the intensive care unit. Blood work will be collected at 4 time points, prior to continuous dialysis therapy initiation, 4-12 hours into therapy, 24 hours into therapy, and at ICU discharge.

Hourly nasopharyngeal and skin temperatures will be collected. Oral temperature will be collected every four hours.

• Study Type: Interventional
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Marat Slessarev, MD; Phone Number: 56560 519-685-8500; Email: Marat.Slessarev@lhsc.on.ca

Study Locations

• Canada
  • Ontario
    • London, Ontario, Canada, N6A 5W9
      • Critical Care Trauma Centre

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• AKI as defined by 2012 AKI KDIGO guidelines requiring CRRT.
• Patient's core temperature between 35°C and 40°C at the time of recruitment.
• Age 18 years old and older.

Exclusion Criteria:

• Hypothermia (patient core temperature <35°C) at the time of recruitment
• Extreme hyperthermia or hyperpyrexia (patient core temperature >40°C) at the time of recruitment.
• Contraindication to cooling (e.g., hemorrhagic shock or severe coagulopathy)
• Patients undergoing targeted temperature management for cardiac arrest.
• Chronic kidney disease stage 5 as defined by CKD KDIGO guidelines [19] requiring renal replacement therapy prior to recruitment.
• Receiving palliative care or immediate plans for withdrawal of life sustaining therapy at the time of recruitment.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Control: Standard of care; Participants in the control group will receive standard-of-care CRRT prescriptions, and have the returning venous blood warmed with an external blood warmer to a temperature of 37°C. The blood warmer temperature will be adjusted by the CRRT nurse as per usual practice to maintain normothermia.
Experimental: Intervention: Cooling; Participants in the intervention group will receive standard of care CRRT prescriptions and have the blood warmer set to 35.5°C, as long as the nasopharyngeal temperature remains above 35.5°C.	Procedure: Dialysis cooling; Cooling the blood in the CRRT circuit during delivery

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Regional Wall Motion Abnormalities	Number of segments undergoing a 20% reduction in longitudinal systolic strain	At the end of delivery of cool blood during continuous dialysis; 12 to 24 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Regional Wall Motion Abnormalities at 7 days	Number of segments undergoing a 20% reduction in longitudinal systolic strain after delivery of cool blood during continuous dialysis	Seven days after the start of cool blood delivery during continuous dialysis
Regional Wall Motion Abnormalities at ICU discharge	Number of segments undergoing a 20% reduction in longitudinal systolic strain at ICU discharge	At ICU discharge, an average of 60 days after the start of cool blood delivery during continuous dialysis
Duration of Continuous Renal Replacement Therapy (CRRT)	Number of hours of CRRT therapy during ICU admission	Through study completion, an average of 60 days
Renal Recovery at 7 days after cool blood continuous dialysis requiring acute kidney injury	Renal recovery may best be defined as a reduction in AKI stage at seven days after the start of cool blood continuous dialysis treatment determined by creatinine level and urine output.	Seven days after the start of cool blood delivery during continuous dialysis
Renal Recovery at 24 hours after cool blood continuous dialysis requiring acute kidney injury	Renal recovery may best be defined as a reduction in AKI stage at 24 hours after the start of cool blood continuous dialysis treatment determined by creatinine level and urine output.	24 hours after the start of cool blood delivery during continuous dialysis
Low blood pressure	Systolic blood pressure less than 90mmHg or more than 20mmHg fall below baseline; 10% increase in vasopressor dose leading to an increase in blood pressure.	Through study completion, an average of 60 days
Cumulative vasopressor dose	Dose of vasopressor drugs - unit dependent on drug	Through study completion, an average of 60 days
Patient's Core Body Temperature (Celsius degrees)	Core body temperature as measured with SpotOn device	Through study completion, an average of 60 days
Temperature of venous blood in return line (Celsius degrees)	Blood temperature measured with SpotOn device	Through study completion, an average of 60 days
Intensive care unit free days	Number of days that a participant has been discharged from the ICU while admitted to the hospital	After an average of 60 days in the ICU
ICU length of stay	Number of days a participant stayed in the ICU	Through study completion, an average of 60 days
Hospital length of stay	Number of days a participant stayed in the hospital	Through study completion, an average of 60 days to hospital discharge
ICU mortality	Mortality rate during ICU admission	Through study completion, an average of 60 days
In Hospital Mortality	Mortality rate during in hospital stay	Through study completion, an average of 60 days to hospital discharge
60-day Mortality	Mortality rate within the 60 day period	From study start to up to 60 days from study start
Temperature correlation between nasopharyngeal, forehead, and oral temperature measurements	To correlate invasive measurements of core body temperature (nasopharyngeal) with non-invasive oral and forehead temperature monitoring using the SpotOn system	From study start to up to 60 days from study start

Collaborators and Investigators

• Sponsor: Lawson Health Research Institute
• Investigators: Principal Investigator: Marat Slessarev, MD, Lawson Health Research Institute

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2020
• Primary Completion (Estimated): November 1, 2021
• Study Completion (Estimated): December 31, 2022

Study Registration Dates

• First Submitted: August 9, 2019
• First Submitted That Met QC Criteria: September 24, 2019
• First Posted (Actual): September 25, 2019

Study Record Updates

• Last Update Posted (Actual): March 13, 2024
• Last Update Submitted That Met QC Criteria: March 12, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Cooling; CRRT
• Additional Relevant MeSH Terms: Kidney Diseases; Urologic Diseases; Renal Insufficiency; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Wounds and Injuries; Acute Kidney Injury
• Other Study ID Numbers: 113951

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No