Efficacy of Add-on Plasma Exchange As an Adjunctive Strategy Against Septic Shock

Официальное название

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

Обзор

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.

Подробное описание

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.

Вмешательства

• Устройство Therapeutic Plasma Exchange (TPE)
  The TPE treatment will be initiated within 6 hrs after randomization. Duration of TPE treatment is approximately 120-180 minutes. An additional second TPE can be performed if the patient remains vasopressor dependent ≥ 0.4 ug/kg/min after 24 hours following the first TPE procedure. Both unfractionated heparin (UFH) and citrate may be used as anticoagulant medication. To ensure treatment comparability between different patients, we will replace plasma in a fixed ratio of 1.2 x the individual pa

Первичные конечные точки

• 28-day mortality [Срок оценки: from randomization up to 28 days following randomization]

Вторичные конечные точки (12)

• Mean daily Sequential Organ Failure Score (SOFA) score over the first 7 days (KEY secondary outcome) [Срок оценки: from randomization up to 7 days following randomization]
• Organ support free days until day 28 (KEY secondary outcome) [Срок оценки: from randomization up to 28 days following randomization]
• 90-day mortality [Срок оценки: from randomization up to 90 days following randomization]
• Intensive Care unit (ICU) length of stay [Срок оценки: from randomization until ICU discharge]
• Hospital length of stay [Срок оценки: from randomization until hospital discharge]
• Basic Hemodynamics [Срок оценки: at days 1-7 following randomization]
• Extended Hemodynamics [Срок оценки: at days 1-7 following randomization]
• Arterial blood gas analysis [Срок оценки: at days 1-7 following randomization]
• Respiratory function [Срок оценки: at days 1-7 following randomization]
• Renal function [Срок оценки: at days 1-7 following randomization and at ICU discharge]
• Liver Function [Срок оценки: at days 1-7 following randomization and at ICU discharge]
• Sepsis associated coagulopathy [Срок оценки: at days 1-7 following randomization]

Критерии участия

Критерии включения

• 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)

Критерии исключения

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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Германия · 21 центр

• St. Joseph Hospital — Berlin
• University Hospital Berlin Charite — Berlin
• University Hospital Bonn — Bonn
• Hospital Braunschweig — Braunschweig
• Hospital Bremerhaven — Bremerhaven
• Hospital Cologne Meerheim — Cologne
• University Hospital Cologne — Cologne
• University Hospital Erlangen — Erlangen
• … и ещё 13 центров

Австрия · 2 центра

• University Hospital Innsbruck — Innsbruck
• University Hospital Vienna — Vienna

Швейцария · 2 центра

• University Hospital Bern — Bern
• University Hospital Zurich — Zurich

Публикации

• 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. PMID 30373638
• 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. PMID 32122366
• 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. PMID 33063613
• 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
• 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
• 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
• David S, Bode C, Stahl K; EXCHANGE-2 Study group. EXCHANGE-2: investigating the efficacy of add-on plasma exchange as an adjunctive strategy against septic shock-a study protocol for a randomized, prospective, multicenter, open-label, controlled, parallel-group trial. Trials. 2023 Apr 15;24(1):277. doi: 10.1186/s13063-023-07300-5. PMID 37061693

Идентификаторы

NCT: NCT05726825 · EXCHANGE-2

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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