Remote Ischemic Preconditioning in Septic Patients (RIPC-ICU)

Effect of Remote Ischemic Preconditioning in Septic Patients on Cell Cycle Arrest Biomarkers - the RIPC-ICU Randomized Clinical Trial

Acute kidney injury is a well-recognized complication in critically ill patients. Up to date there is no clinically established method to reduce the incidence or the severity of acute kidney injury.

Remote ischemic preconditioning (RIPC) will be induced by three cycles of upper limb ischemia.

The aim of the study is to reduce the incidence of AKI by implementing remote ischemic preconditioning (identified by the urinary biomarkers tissue inhibitor of metalloproteinases-2 (TIMP-2) and insulin-like growth factor-binding protein 7(IGFBP7)

Study Overview

• Status: Recruiting
• Conditions: Sepsis; Acute Kidney Injury; Critically Ill
• Intervention / Treatment: Procedure: Remote ischemic preconditioning (RIPC); Procedure: Sham RIPC

Detailed Description

Acute kidney injury (AKI) is a common complication in critically ill patients with sepsis. To date, there is no pharmacological option to treat or prevent AKI.

Ischemic conditioning is an innate tissue adaptation elicited by ischemia that mediates local and remote organ protection against subsequent exposure to the same or other injury.

The aim of this trial is to evaluate the effects of remote ischemic conditioning in critically ill patients on acute kidney injury.

• Study Type: Interventional
• Enrollment (Estimated): 64
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Melanie Meersch-Dini, MD; Phone Number: +49-251-8347255; Email: meersch@uni-muenster.de

Study Locations

• Germany
  • Münster, Germany, 48149
    • Recruiting
    • University Hospital Münster; Department of Anesthesiology, Intensive Care Medicine and Pain Medicine
    • Contact: Meersch, MD; Email: aki@uni-muenster.de

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Adult patients (age ≥18 years)
• Critically ill patients with sepsis < 12 hours
• Invasive ventilation for at least 24 hours (propofol-free-sedation) and/or vasopressor therapy
• Unrestricted intensive care for at least 72 hours
• Written informed consent

Exclusion Criteria:

• Pre-existing AKI
• (Glomerulo-)nephritis, interstitial nephritis, vasculitis
• Chronic kidney disease with estimated glomerular filtration rate (eGFR) < 30 ml/min/1.73m²
• Chronic dialysis dependency
• Kidney transplant in the last 12 months
• Oral antidiabetics, sulfonamides or nicorandil
• Pregnancy or breastfeeding
• Do-not-reanimate order
• Participation in another interventional trial involving kidney outcomes within the last 3 months
• Dependency on the investigator or center

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Intervention Group; Remote ischemic preconditioning (RIPC) Three Cycles of 5-min upper limb ischemia. If there is no response this will be followed by 2 cycles of 10-min upper-limb ischemia.	Procedure: Remote ischemic preconditioning (RIPC); 3 cycles of 5 min inflation of a blood-pressure cuff to 200 millimetres of mercury (mmHG) (or at least to a pressure 50 mmHG higher than the systolic arterial pressure) to one upper arm followed by 5 min reperfusion with the cuff deflated. In Non-Responder two additional cycles of 10 min cuff inflation will be performed.
Sham Comparator: Control Group; Three cycles of 5- min upper limb sham ischemia.	Procedure: Sham RIPC; 3 cycles of 5 min inflation of a blood-pressure cuff to 20 mmHG to one upper arm followed by 5 min reperfusion with the cuff deflated. In Non-Responder two additional cycles of 10 min cuff inflation will be performed

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
1. kidney damage after cardiac surgery identified by the difference between [TIMP-2]*[IGFBP7] levels 24h after randomization and [TIMP-2]*[IGFBP7] levels at randomization	from randomization to 24 hours after randomization

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Acute Kidney Injury (AKI) according to the Kidney Disease: Improving Global Outcomes (KDIGO) criteria		72 hours after the onset of sepsis
Severity of AKI	The severity for AKI is classified according to the KDIGO criteria	72 hours after the onset of sepsis
Need for renal replacement therapy	Number of patients with renal replacement therapy	72 hours after the onset of sepsis
Recovery of kidney function	defined as complete recovery: serum-creatinine ≤0.5 mg/dl higher than baseline; partial recovery: serum creatinine >0.5 mg/dl higher than baseline but no dialysis-dependence; non-recovery: patients who remained dialysis-dependent	day 90 after the onset of sepsis
Mortality		day 90 after the onset of sepsis
Major adverse kidney events (MAKE) Composite endpoint consisting of death, renal replacement therapy, and persistent severe AKI lasting for 72 hours or more		day 90 after the onset of sepsis
Length of Intensive Care Unit (ICU) stay		up to 90 days after onset of sepsis
Length of hospital stay		up to 90 days after onset of sepsis

Other Outcome Measures

Outcome Measure	Time Frame
Add-on Study (Analysis of further proteins)	from randomization until 24 hours after randomization

Collaborators and Investigators

• Sponsor: Westfälische Wilhelms-Universität Münster
• Investigators: Principal Investigator: Melanie Meersch-Dini, MD, University Hospital Muenster, Dept. of Anesthesiology, Intensive Care Therapy and Pain Medicine

Study record dates

Study Major Dates

• Study Start (Actual): May 11, 2023
• Primary Completion (Estimated): October 1, 2024
• Study Completion (Estimated): January 1, 2025

Study Registration Dates

• First Submitted: March 30, 2023
• First Submitted That Met QC Criteria: April 13, 2023
• First Posted (Actual): April 26, 2023

Study Record Updates

• Last Update Posted (Actual): June 22, 2023
• Last Update Submitted That Met QC Criteria: June 20, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Kidney Diseases; Urologic Diseases; Disease Attributes; Renal Insufficiency; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Critical Illness; Acute Kidney Injury
• Other Study ID Numbers: AnIt22-06

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