Therapeutic Plasmaexchange in Early Septic Shock (EXCHANGE)

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

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.

Study Overview

• Status: Completed
• Conditions: Septic Shock
• Intervention / Treatment: Device: TPE

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Phase 2

Contacts and Locations

Study Locations

• Germany
  • Bonn, Germany, 53127
    • University Hospital Bonn
  • Lower Saxony
    • Hannover, Lower Saxony, Germany, 30625
      • Hannover Medical School

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: TPE; additive singular therapeutic plasma Exchange (TPE) using fresh frozen Plasma (FFP) as replacement fluid	Device: TPE; singular Therapeutic Plasma Exchange using fresh frozen Plasma as replacement fluid
No Intervention: SMT; Standard medical Treatment (SMT) for septic shock following the present surviving sepsis guidelines

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Hannover Medical School
• Investigators: Principal Investigator: Sascha David, MD, Clinic for nephrology; Principal Investigator: Klaus Stahl, MD, Clinic for gastroenterology and hepatology

Publications and helpful links

General Publications

• David S, Bode C, Putensen C, Welte T, Stahl K; EXCHANGE study group. Adjuvant therapeutic plasma exchange in septic shock. Intensive Care Med. 2021 Mar;47(3):352-354. doi: 10.1007/s00134-020-06339-1. Epub 2021 Jan 20. No abstract available.
• Stahl K, Wand P, Seeliger B, Wendel-Garcia PD, Schmidt JJ, Schmidt BMW, Sauer A, Lehmann F, Budde U, Busch M, Wiesner O, Welte T, Haller H, Wedemeyer H, Putensen C, Hoeper MM, Bode C, David S. Clinical and biochemical endpoints and predictors of response to plasma exchange in septic shock: results from a randomized controlled trial. Crit Care. 2022 May 12;26(1):134. doi: 10.1186/s13054-022-04003-2.
• Stahl K, Hillebrand UC, Kiyan Y, Seeliger B, Schmidt JJ, Schenk H, Pape T, Schmidt BMW, Welte T, Hoeper MM, Sauer A, Wygrecka M, Bode C, Wedemeyer H, Haller H, David S. Effects of therapeutic plasma exchange on the endothelial glycocalyx in septic shock. Intensive Care Med Exp. 2021 Nov 24;9(1):57. doi: 10.1186/s40635-021-00417-4.

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2018
• Primary Completion (Actual): July 31, 2020
• Study Completion (Actual): August 31, 2020

Study Registration Dates

• First Submitted: January 13, 2020
• First Submitted That Met QC Criteria: January 14, 2020
• First Posted (Actual): January 18, 2020

Study Record Updates

• Last Update Posted (Actual): February 10, 2021
• Last Update Submitted That Met QC Criteria: February 6, 2021
• Last Verified: February 1, 2021

More Information

Terms related to this study

• Keywords: Septic shock; Sepsis; Therapeutic plasma exchange
• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Sepsis; Shock, Septic; Shock
• Other Study ID Numbers: EXCHANGE 2786-2015

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: pre-defined substudies

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No