Clinical trial NCT04231994: Therapeutic Plasmaexchange in Early Septic Shock
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Septic Shock
Keywords: Septic shock
Therapeutic plasma exchange
Sepsis
Lead sponsor: Hannover Medical School
Sponsor class: OTHER
First posted: 2020-01-18
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Norepinephrine dose
timeFrame: 6 hours after randomization
Secondary outcomes:
measure: Mean Sequential organ failure assessment (SOFA) score
timeFrame: day 1-8 following randomization
measure: percent change of ADAMTS-13 activity from baseline
timeFrame: 6 hours after randomization
measure: percent change of activated Protein C activity from baseline
timeFrame: 6 hours after randomization
measure: percent change of permeability factors angiopoietin-1, -2 and sTie-2 from baseline
timeFrame: 6 hours after randomization
measure: 28 day survival
timeFrame: after 28 days following randomization
Other outcomes:
Locations:
city: Hannover
country: Germany
facility: Hannover Medical School
state: Lower Saxony
city: Bonn
country: Germany
facility: University Hospital Bonn
Study officials:
affiliation: Clinic for nephrology
name: Sascha David, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Clinic for gastroenterology and hepatology
name: Klaus Stahl, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.