REmote Ischemic COnditioning in Septic Shock

Study Overview
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Brief Summary
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Septic shock remains a major public health problem in industrialized countries, with a mortality rate as high as 50%, largely related to multiple organ dysfunction. In addition to dysregulated inflammatory response, the pathophysiology of organ failures in septic shock involves ischemia-reperfusion processes. Remote ischemic conditioning is a therapeutic strategy for protecting organs against the detrimental effects of ischemia-reperfusion injury. The objective of the present study is to determine whether remote ischemic conditioning can limit the severity of organ failure in patients with septic shock.

Official Title
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REmote Ischemic COnditioning in Septic Shock: The RECO-Sepsis Study

Conditions
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Septic Shock

Intervention / Treatment
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* Device: Remote Ischemic conditioning
* Device: Patients with no remote ischemic conditioning


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥ 18 years Hospitalization in an intensive care unit for less than 24 hours Septic shock evolving for less than 12 hours defined as: Documented or suspected infection Norepinephrine administration to maintain a mean arterial pressure ≥ 65 mmHg after volemia correction Lactatemia > 2 mmol/L at least once in the past 12 hours before inclusion Written informed consent signed by the patient or by a next of kin or oral consent given by the patient and as soon as permitted by the clinical state written informed consent signed by the patient. Exclusion Criteria: Patient who has expressed the wish not to be resuscitated Contraindication of the use of brachial cuff on both arms Intercurrent pathology with an expected life expectancy of less than 24 hours Cardiac arrest Female patients currently pregnant or women of childbearing age who are not using contraception Previous inclusion in RECO-Sepsis study Previous inclusion in another clinical study Patients without health coverage

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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Remote ischemic conditioning<br>A brachial cuff is positioned around the arm of the patient. The remote ischemic conditioning consists in alternative inflations and deflations of the brachial cuff. | Device: Remote Ischemic conditioning<br>* A brachial cuff is positioned around the arm of the patient. Four cycles of [5 min brachial cuff inflation at 200 mmHg followed by 5 min of cuff deflation] started as soon as possible after randomization. The intervention is repeated at 12 and 24 hours after inclusion.<br>|
| Other: Control group<br>A brachial cuff is positioned around the arm of the patient. No inflation or deflation is made. | Device: Patients with no remote ischemic conditioning<br>* A brachial cuff is positioned around the arm of the patient and no inflation or deflation is made.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Average SOFA score (Sequential Organ Failure Assessment) | The SOFA score ranges from 0 to 24 (higher scores indicate more severe organ failure), with 0 to 4 points assigned for each of 6 organ dysfunctions (ie, central nervous system, cardiovascular, respiratory, renal, coagulation, and liver). | 96 hours. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Average SOFA score without the neurologic sub-score. | The SOFA score without the neurologic subscore ranges from 0 to 20 (higher scores indicate more severe organ failure), with 0 to 4 points assigned for each of 5 organ dysfunctions (ie, cardiovascular, respiratory, renal, coagulation, and liver). | 96 hours. | 
| SOFA score. |  | 24 hours | 
| SOFA score. |  | 48 hours | 
| SOFA score. |  | 72 hours | 
| SOFA score. |  | 96 hours | 
| Variations of SOFA score (delta-SOFA) |  | 24 hours | 
| SOFA sub-scores for each organs |  | 48 hours | 
| SOFA sub-scores for each organs |  | 72 hours | 
| SOFA sub-scores for each organs |  | 96 hours | 
| Survival without organ support |  | Day 28 | 
| Intensive care unit (ICU) length of stay. |  | Day 90 | 
| Hospital length of stay |  | Day 90 | 
| All-cause mortality |  | Day 90 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Intensive care, septic shock, multiple organ failure, Ischemia-reperfusion, ischemic conditioning, remote conditioning, SOFA score