Therapeutic Plasmaexchange in Early Septic Shock

NCT04231994 | Completed Phase 2

• 1 other identifier: EXCHANGE 2786-2015
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 2

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.

Conditions

Septic Shock

Keywords

Septic shock; Therapeutic plasma exchange; Sepsis

Outcome Measures

Primary Outcomes (1)

• Norepinephrine dose

  Vasopressor dose reduction as indicator of shock reversal

  6 hours after randomization

Secondary Outcomes (5)

• Mean Sequential organ failure assessment (SOFA) score

  day 1-8 following randomization

• percent change of ADAMTS-13 activity from baseline

  6 hours after randomization

• percent change of activated Protein C activity from baseline

  6 hours after randomization

• percent change of permeability factors angiopoietin-1, -2 and sTie-2 from baseline

  6 hours after randomization

• 28 day survival

  after 28 days following randomization

Study Arms (2)

TPE

EXPERIMENTAL

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

Device: TPE

SMT

NO INTERVENTION

Standard medical Treatment (SMT) for septic shock following the present surviving sepsis guidelines

Interventions

TPE DEVICE

singular Therapeutic Plasma Exchange using fresh frozen Plasma as replacement fluid

TPE

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

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

Sponsors & Collaborators

• Hannover Medical School: lead

Study Sites (2)

Hannover Medical School

Hanover, Lower Saxony, 30625, Germany

Location

University Hospital Bonn

Bonn, 53127, Germany

Location

Related Publications (3)

• 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.

  PMID: 33471132 RESULT

• 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.

  PMID: 35551628 DERIVED

• 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.

  PMID: 34817751 DERIVED

Related Links

• Related Info

MeSH Terms

Conditions

Shock, Septic; Sepsis

Condition Hierarchy (Ancestors)

Infections; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Shock

Study Officials

• Sascha David, MD

  Clinic for nephrology

  PRINCIPAL INVESTIGATOR

• Klaus Stahl, MD

  Clinic for gastroenterology and hepatology

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Dr. Klaus Stahl, Fellow Gastroenterology and Critical Care Medicine

Study Record Dates

• First Submitted: January 13, 2020
• First Posted: January 18, 2020
• Study Start: June 1, 2018
• Primary Completion: July 31, 2020
• Study Completion: August 31, 2020
• Last Updated: February 10, 2021

Record last verified: 2021-02

Data Sharing

• IPD Sharing: Will share

Locations

DE (2)