Low-intensity Versus Medium-intensity Continuous Kidney Replacement Therapy for Critically Ill Patients (LIMIT)

Low-Intensity Versus Medium-Intensity Continuous Kidney Replacement Therapy for Critically Ill Patients (LIMIT): A Multicenter Randomized Clinical Trial

This clinical trial aims to investigate whether the low treatment intensity (12 mL/kg/hr, low-dose hemodialysis/filtration) or the medium treatment intensity (25 mL/kg/hr, standard-dose hemodialysis/filtration) is more effective and safer for continuous renal replacement therapy in critically ill patients.

Study Overview

• Status: Recruiting
• Conditions: Acute Kidney Injury Requiring Continuous Renal Replacement Therapy
• Intervention / Treatment: Drug: Dialysate fluid, Filtration replacement fluid

• Study Type: Interventional
• Enrollment (Estimated): 400
• Phase: Phase 2; Phase 3

Contacts and Locations

• Study Contact: Name: Tomoko Fujii, MD,PhD; Phone Number: +81 3 3433 1111; Email: tofujii-tky@umin.net

Study Locations

• Japan
  • Fukui, Japan, 910 1193
    • Not yet recruiting
    • University of Fukui Hospital
    • Contact: Aiko Tanaka, MD, PhD; Phone Number: +81 776 61 3111
  • Hiroshima, Japan, 734 0037
    • Not yet recruiting
    • Hiroshima University Hospital
    • Contact: Mayumi Higashi, MD, PhD; Phone Number: +81 82 257 5555
  • Ibaraki, Japan, 300 0028
    • Recruiting
    • Tsuchiura Kyodo General Hospital
    • Contact: Akira Endo, MD, PhD; Phone Number: +81 29 830 3711
  • Osaka, Japan, 565 0871
    • Not yet recruiting
    • Osaka University Hospital
    • Contact: Naoya Iguchi, MD, PhD; Phone Number: +81 6 6879 5111
  • Tochigi, Japan, 329 0498
    • Not yet recruiting
    • Jichi Medical University Hospital
    • Contact: Hisashi Imahase, MD
  • Tokyo, Japan, 105 8471
    • Recruiting
    • Jikei University Hospital
    • Contact: Tomoko Fujii, MD, PhD; Phone Number: 4070 +81 3 3433 1111; Email: tofujii-tky@umin.net
  • Tokyo, Japan, 160 0016
    • Recruiting
    • Keio University Hospital
    • Contact: Ryo Yamamoto, MD, PhD; Phone Number: +81 3 3353 1211
  • Wakayama, Japan, 641 8509
    • Not yet recruiting
    • Wakayama Medical University Hospital
    • Contact: Kyohei Miyamoto, MD, PhD; Phone Number: +81 73 447 2300

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria: Patient who meets all of the following criteria and who has given informed consent.

1. Adults (18 years of age or older, regardless of the time since ICU admission) currently admitted to an intensive care unit*.

   *Includes high care units, where continuous monitoring is conducted and intensive care physicians are in charge of medical care.

2. A diagnosis of acute kidney injury is made according to the Kidney Disease: Improving Global Outcomes (KDIGO) international diagnostic criteria (one of the following is met)

   • Serum creatinine increased by more than 0.3 mg/dL within 48 hours
   • Serum creatinine increased more than 1.5-fold from baseline and the increase is considered to have occurred within 7 days
   • Oliguria (< 0.5 mL/kg/hr) lasting more than 6 hours
3. The treating intensivist believes that continuous kidney replacement therapy is necessary

Exclusion Criteria: Patient who meets any of the following exclusion criteria will be excluded.

1. Receiving chronic dialysis or scheduled for initiation of chronic dialysis
2. Undergoing any kidney replacement therapy or blood purification therapy within 48 hours
3. When kidney replacement therapy using other dialysate or replacement fluids, such as citrate dialysis, is preferred due to coexisting bleeding disorders or allergy to acetate
4. Concomitant blood purification therapy other than hemofiltration/dialysis, such as plasma exchange
5. The patient is in a very critical condition and the treating physician believes that survival for more than 24 hours is unlikely
6. Previous participation in the study
7. After receiving a full explanation of the study and with full understanding, a patient do not consent to participate in the study of their own (or their substitute decision maker's) will.
8. The principal investigator (or an investigator) thinks it to be inappropriate to participate in this study.

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
Experimental: Low intensity; 12 mL/kg/hr	Drug: Dialysate fluid, Filtration replacement fluid; Dose of continuous hemodialysis and/or hemofiltration
Active Comparator: Medium intensity; 25 mL/kg/hr	Drug: Dialysate fluid, Filtration replacement fluid; Dose of continuous hemodialysis and/or hemofiltration

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
28-day kidney replacement therapy free days	Composite endpoint of death and duration of kidney replacement therapy at 28 days	28 days or hospital discharge whichever comes first

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ICU mortality		90 days or hospital discharge whichever comes first
Hospital mortality		90 days or hospital discharge whichever comes first
Dialysis dependence at hospital discharge		90 days or hospital discharge whichever comes first
28-day vasopressor-free days		28 days or hospital discharge whichever comes first
28-day ventilator-free days		28 days or hospital discharge whichever comes first
Serum creatinine level at the end of kidney replacement therapy	Serum creatinine level on the day of final kidney replacement therapy and the day before	90 days or hospital discharge whichever comes first
24-hour urine output at the end of kidney replacement therapy	24-hour urine output on the day of final kidney replacement therapy and the day before	90 days or hospital discharge whichever comes first

Other Outcome Measures

Outcome Measure	Time Frame
Hypokalemia	up to 7 days of continuous kidney replacement therapy
Hypophosphatemia	up to 7 days of continuous kidney replacement therapy
Sodium bicarbonate solutions that administered	up to 7 days of continuous kidney replacement therapy

Collaborators and Investigators

• Sponsor: Jikei University School of Medicine
• Collaborators: Keio University; Wakayama Medical University; Jichi Medical University; University of Fukui; Tsuchiura Kyodo General Hospital
• Investigators: Study Chair: Tomoko Fujii, MD,PhD, Jikei University School of Medicine

Study record dates

Study Major Dates

• Study Start (Actual): October 30, 2023
• Primary Completion (Estimated): December 1, 2025
• Study Completion (Estimated): September 1, 2026

Study Registration Dates

• First Submitted: August 16, 2023
• First Submitted That Met QC Criteria: August 21, 2023
• First Posted (Actual): August 28, 2023

Study Record Updates

• Last Update Posted (Actual): November 28, 2023
• Last Update Submitted That Met QC Criteria: November 26, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Kidney Diseases; Urologic Diseases; Renal Insufficiency; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Acute Kidney Injury; Pharmaceutical Solutions; Dialysis Solutions
• Other Study ID Numbers: JKI23-002; jRCTs031230292 (Registry Identifier: Japan Registry of Clinical Trials)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

Drug and device information, study documents

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