Therapeutic Plasmaexchange in Early Septic Shock

Phase 2

Completed

• Conditions: Septic Shock
• Interventions: Device: TPE

• Registration Number: NCT04231994
• Lead Sponsor: Hannover Medical School

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2018-06-01
• Study First Submitted: 2020-01-13
• Study First Submitted QC: 2020-01-14
• Study First Posted: 2020-01-18
• Primary Completion: 2020-07-31
• Study Completion: 2020-08-31
• Status Verified: 2021-02
• Last Update Submitted: 2021-02-06
• Last Update Posted: 2021-02-10

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 40

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

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Exclusion Criteria

• Age<18 years and > 80 years
• Pregnancy
• Known history of transfusion reactions

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
TPE	TPE	additive singular therapeutic plasma Exchange (TPE) using fresh frozen Plasma (FFP) as replacement fluid

Primary Outcome Measures

Name	Time	Method
Norepinephrine dose	6 hours after randomization	Vasopressor dose reduction as indicator of shock reversal

Secondary Outcome Measures

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

Trial Locations

Locations (2)

University Hospital Bonn; 🇩🇪 Bonn, Germany

Hannover Medical School; 🇩🇪 Hannover, Lower Saxony, Germany