Therapeutic Plasmaexchange in Early Septic Shock

Study Overview
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Brief Summary
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Sepsis is defined by the occurrence of critical organ dysfunction in the context of infection. Unfortunately, its incidence appears to be rising, and the mortality of septic shock remains extraordinary high (> 60%). Death in sepsis arises from shock and multi organ dysfunction that are - at least in part - triggered by an inadequate response of the host's immune system to the infection. Given the injurious role of 1) this overwhelming immune response and 2) the consumption of protective plasmatic factors (e.g. vWF cleaving proteases, hemostatic factors etc.) while the disease is progressing the investigators hypothesize that early therapeutic plasma exchange (TPE) in the most severely ill individuals might improve hemodynamics, oxygenation and ultimately survival. This therapeutic strategy combines 2 major aspects in 1 procedure: 1. removal of harmful circulating molecules and 2. replacement of protective plasma proteins. The investigators designed the EXCHANGE trial to analyze in a randomized fashion the benefit of TPE as an add-on treatment to state of the art standard sepsis care. Only patients with early septic shock (< 24 hrs) and high catecholamine doses (norepinephrine > 0.4 ug/kg body weight/min) will be included. Those in the treatment group will receive 1 TPE within 2 hours following randomization. The primary outcome is norepinephrine dose 6 hrs after randomization. The recruitment period is 2 years and will be performed at the Hannover medical School University hospital in Germany. Secondary endpoints (including organ dysfunction as well as biochemical markers of inflammation and coagulation) will be assessed on day 1-8 and day 28 after TPE. The investigators hope to demonstrate a potential benefit of an additive treatment approach to improve the outcome of patients suffering from septic shock.

Official Title
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Prospective, Randomized, Single-center, Open-label, Parallel-group Trial Investigating the Efficacy of Therapeutic Plasma Exchange as an Adjunctive Strategy Against Early Septic Shock - Effect on Hemodynamics and Biochemical Markers

Conditions
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Septic Shock

Intervention / Treatment
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* Device: TPE


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Onset of septic shock within less than 24 hrs Norepinephrine dose of ≥ 0.4 ug/kg/min bodyweight (target mean arterial pressure ≥ 65 mmHg) ≥ 30 min Exclusion Criteria: Age<18 years and > 80 years Pregnancy Known history of transfusion reactions

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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: TPE<br>additive singular therapeutic plasma Exchange (TPE) using fresh frozen Plasma (FFP) as replacement fluid | Device: TPE<br>* singular Therapeutic Plasma Exchange using fresh frozen Plasma as replacement fluid<br>|
| No Intervention: SMT<br>Standard medical Treatment (SMT) for septic shock following the present surviving sepsis guidelines | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Norepinephrine dose | Vasopressor dose reduction as indicator of shock reversal | 6 hours after randomization | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Sequential organ failure assessment (SOFA) score | SOFA score as indicator of organ dysfunction | day 1-8 following randomization | 
| percent change of ADAMTS-13 activity from baseline | (will only be analyzed in the Hannover cohort) | 6 hours after randomization | 
| percent change of activated Protein C activity from baseline | (will only be analyzed in the Hannover cohort) | 6 hours after randomization | 
| percent change of permeability factors angiopoietin-1, -2 and sTie-2 from baseline | permeability and anti-permeability factors (will only be analyzed in the Hannover cohort) | 6 hours after randomization | 
| 28 day survival |  | after 28 days following randomization | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Septic shock, Therapeutic plasma exchange, Sepsis