Clinical trial NCT05726825: Efficacy of Add-on Plasma Exchange As an Adjunctive Strategy Against Septic Shock
Official title: Randomized, Prospective, Multicenter, Open-label, Controlled, Parallel-group Trial Investigating the Efficacy of Add-on Plasma Exchange As an Adjunctive Strategy Against Septic Shock - 2
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Septic Shock
Keywords: Septic Shock
Sepsis
Multi-organ failure
Extracorporeal therapy
Plasmapheresis
Lead sponsor: Hannover Medical School
Sponsor class: OTHER
First posted: 2023-02-14
Enrollment: 274
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: Randomized, prospective, multicenter, open-label, controlled, parallel-group interventional trial to test the adjunctive effect of therapeutic plasma exchange in patients with early septic shock.

Detailed description: Sepsis is defined as a life-threatening organ dysfunction caused by a dysregulated host response to an infection; in septic shock profound circulatory, cellular and metabolic abnormalities are associated with an even higher mortality. Sepsis is a major healthcare problem, affecting millions of individuals around the world each year. Its incidence appears to be rising, and the mortality caused by septic shock in Germany in 2015 remains extraordinarily high (58.8%). It is well known - from the pathophysiological point of view - that these patients do not die from their infection per se but rather from multiple organ failure caused by their own overwhelming host response. This fact is so fundamental that it has been implemented as a key part of the 2016 sepsis definition (SEPSIS-3). Despite tremendous efforts during the last decades, innovative approaches targeting this fundamental hallmark of the disease, thereby reducing organ dysfunction, are lacking. Undoubtedly, there is an unmet need to expand the current standard of care for these patients by a more specific intervention.

The investigators hypothesize that early Therapeutic Plasma Exchange (TPE) in the most severely ill individuals will dampen the injurious maladaptive host response by removing injurious mediators thereby limiting organ dysfunction. The potential impact of this trial is of immense clinical relevance as it evaluates a promising adjunctive treatment option for a patient cohort suffering from an extraordinary high mortality. A positive trial result could truly change the current standard of care (SOC) - that is mostly supportive - of septic shock patients. Of note, there is neither a patent nor a direct commercial interest in such a trial.

Eligibility criteria: Inclusion Criteria:

* New onset of septic shock (\< 24 hrs), (SEPSIS-3 definition)
* Norepinephrine (NE) dose ≥ 0.4 μg/kg/min ≥ 30 min OR NE ≥ 0.3 μg/kg/min + vasopressin (any dose)
* Established vascular access suitable for plasma exchange independent of study inclusion (due to established indication of RRT, expected need for RRT within the next 48 hours or other medical reasons as assessed by treating physician team)

Exclusion Criteria:

* Age \< 18 or \> 80 years
* Urogenital focus of infection
* Pregnancy
* Heparin-induced thrombocytopenia
* Known reaction against fresh frozen plasma (FFP)

Primary outcomes:
measure: 28-day mortality
timeFrame: from randomization up to 28 days following randomization
Secondary outcomes:
measure: Mean daily Sequential Organ Failure Score (SOFA) score over the first 7 days (KEY secondary outcome)
timeFrame: from randomization up to 7 days following randomization
measure: Organ support free days until day 28 (KEY secondary outcome)
timeFrame: from randomization up to 28 days following randomization
measure: 90-day mortality
timeFrame: from randomization up to 90 days following randomization
measure: Intensive Care unit (ICU) length of stay
timeFrame: from randomization until ICU discharge
measure: Hospital length of stay
timeFrame: from randomization until hospital discharge
measure: Basic Hemodynamics
timeFrame: at days 1-7 following randomization
measure: Extended Hemodynamics
timeFrame: at days 1-7 following randomization
measure: Arterial blood gas analysis
timeFrame: at days 1-7 following randomization
measure: Respiratory function
timeFrame: at days 1-7 following randomization
measure: Renal function
timeFrame: at days 1-7 following randomization and at ICU discharge
measure: Liver Function
timeFrame: at days 1-7 following randomization and at ICU discharge
measure: Sepsis associated coagulopathy
timeFrame: at days 1-7 following randomization
measure: Inflammatory response
timeFrame: at days 1-7 following randomization
measure: Cardiac function
timeFrame: at days 1-7 following randomization and at ICU discharge
measure: Secondary infections
timeFrame: from randomization until hospital discharge
Other outcomes:
measure: Safety Endpoints
timeFrame: from randomization until day 7 following randomization
Locations:
city: Innsbruck
country: Austria
facility: University Hospital Innsbruck
city: Vienna
country: Austria
facility: University Hospital Vienna
city: Berlin
country: Germany
facility: St. Joseph Hospital
city: Berlin
country: Germany
facility: University Hospital Berlin Charite
city: Bonn
country: Germany
facility: University Hospital Bonn
city: Braunschweig
country: Germany
facility: Hospital Braunschweig
city: Bremerhaven
country: Germany
facility: Hospital Bremerhaven
city: Cologne
country: Germany
facility: Hospital Cologne Meerheim
city: Cologne
country: Germany
facility: University Hospital Cologne
city: Erlangen
country: Germany
facility: University Hospital Erlangen
city: Essen
country: Germany
facility: University Hospital Essen
city: Halle
country: Germany
facility: University Hospital Halle
city: Hamburg
country: Germany
facility: University Hospital Hamburg (UKE)
city: Hannover
country: Germany
facility: Hannover Medical School Anesthesiology
city: Hannover
country: Germany
facility: Hannover Medical School Internal Medicine
city: Heidelberg
country: Germany
facility: University Hospital Heidelberg
city: Jena
country: Germany
facility: University Hospital Jena
city: Kiel
country: Germany
facility: University Hospital Kiel
city: Magdeburg
country: Germany
facility: Hospital Magdeburg
city: Muenster
country: Germany
facility: University Hospital Muenster Anesthesiology
city: Munich
country: Germany
facility: University Hospital Munich (TUM) Anesthesiology
city: Munich
country: Germany
facility: University Hospital Munich (TUM) Internal Medicine
city: Rostock
country: Germany
facility: University Hospital Rostock
city: Bern
country: Switzerland
facility: University Hospital Bern
city: Zurich
country: Switzerland
facility: University Hospital Zurich
Study officials:
affiliation: University of Zurich
name: Sascha David, Prof. Dr.
role: PRINCIPAL_INVESTIGATOR
affiliation: Hannover Medical School
name: Klaus Stahl, PD Dr.
role: PRINCIPAL_INVESTIGATOR
affiliation: University Hospital, Bonn
name: Christian Bode, PD Dr.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Knaup H, Stahl K, Schmidt BMW, Idowu TO, Busch M, Wiesner O, Welte T, Haller H, Kielstein JT, Hoeper MM, David S. Early therapeutic plasma exchange in septic shock: a prospective open-label nonrandomized pilot study focusing on safety, hemodynamics, vascular barrier function, and biologic markers. Crit Care. 2018 Oct 30;22(1):285. doi: 10.1186/s13054-018-2220-9.
citation: Stahl K, Schmidt JJ, Seeliger B, Schmidt BMW, Welte T, Haller H, Hoeper MM, Budde U, Bode C, David S. Effect of therapeutic plasma exchange on endothelial activation and coagulation-related parameters in septic shock. Crit Care. 2020 Mar 2;24(1):71. doi: 10.1186/s13054-020-2799-5.
citation: Stahl K, Bikker R, Seeliger B, Schmidt JJ, Schenk H, Schmidt BMW, Welte T, Haller H, Hoeper MM, Brand K, David S. Effect of Therapeutic Plasma Exchange on Immunoglobulin Deficiency in Early and Severe Septic Shock. J Intensive Care Med. 2021 Dec;36(12):1491-1497. doi: 10.1177/0885066620965169. Epub 2020 Oct 16.
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, 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.
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.