Remote Ischemic Preconditioning in Septic Patients

Study Overview
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Brief Summary
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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)

Detailed Description
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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.

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

Conditions
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Critically Ill, Acute Kidney Injury, Sepsis

Intervention / Treatment
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* Procedure: Remote ischemic preconditioning (RIPC)
* Procedure: Sham RIPC


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intervention Group<br>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)<br>* 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.<br>|
| Sham Comparator: Control Group<br>Three cycles of 5- min upper limb sham ischemia. | Procedure: Sham RIPC<br>* 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<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 |