Hemoadsorpion in Patients With Septic Shock: Efficacy and Safety Evaluation (HAdSS)
Hemoadsorpion in Patients With Septic Shock: Efficacy and Safety Evaluation. A Pilot Multicenter Randomized Controlled Trial
Hemoadsorpion in Patients With Septic Shock: Efficacy and Safety Evaluation. A Pilot Multicenter Randomized Controlled Trial.
The goal of this clinical trial is the estimation of the efficacy and safety of hemoadsorption procedures (LPS (Lipopolysaccharide) and inflammatory mediators adsorption) in participants with septic shock.
The main questions it aims to answer are:
Does hemoadsorption decrease the severity of MODS (multiple organ disfunction syndrome)?
The study will include participants aged 18 to 80 years with a verified diagnosis of septic shock according to SEPSIS 3 criteria, diagnosed within 12 hours, and a SOFA (sequential organ failure assessment) score of 9 or more.
In addition to Standard of Care (SOC), blood purification, including hemoadsorption, will be used. The minimum waiting time after diagnosis of septic shock and initiation of basic therapy before inclusion of the patient in the study therapy is 4 hours.
The choice of procedure will be based on the EAA (Endotoxin Activity Assay) result:
- for an EAA level of 0.6-0.9, selective lipopolysaccharide (LPS) adsorption with duration from 2 to 10 hours;
- for an EAA level less than 0.6, inflammatory mediator adsorption with duration from 6 to 12 hours.
The choice of a specific adsorbers within the LPS and inflammatory mediator adsorption group will be based on randomization.
The use of LPS adsorption is planned based on randomization: Toramyxin R-20 or Efferon LPS. The use of inflammatory mediator adsorption is planned based on randomization: Jafron (HA 330) or CytoSorb.
Descripción general del estudio
Estado
Condiciones
Intervención / Tratamiento
Descripción detallada
Every participant will receive 2 adsorption procedures. The second procedure will be initiated no later than 24 hours after the initiation of the first procedure.
LPS adsorption will be performed in 38 participants (Efferon LPS in 19 participants and Toramyxin in 19 participants), two procedures per participant.
Inflammatory mediator adsorption will be performed in 38 participants (Jafron HA 330 in 19 participants and CytoSorb in 19 participants), two procedures per participant.
Sample size calculations were performed separately for each treatment cohort. For the endotoxemia cohort (EAA level of 0.6-0.9), this randomized trial is designed to compare Efferron LPS and Toraymyxin with respect to change in SOFA score at 72 hours.
At present, no universally accepted minimal clinically important difference (MCID) has been established for the SOFA score in participants with septic shock. Therefore, the assumed treatment effect was derived from published evidence and expert clinical judgment.
In the EUPHAS trial, polymyxin B hemoperfusion was associated with a mean reduction in SOFA score of approximately 3.4 points at 72 hours, whereas minimal change was observed in the control group. Similarly, the LASSO study demonstrated substantial improvement in organ dysfunction following endotoxin adsorption therapy.
For the inflammatory mediator adsorption cohort (EAA level less than 0.6), this randomized trial is designed to compare CytoSorb and Jafron HA 330 with respect to change in SOFA score at 72 hours.
In the retrospective study Mehta et al., CytoSorb hemoperfusion was associated with a mean reduction in SOFA score of approximately 2.0 points after treatment in survival group. Similarly, the case series Onuk et al. demonstrated substantial improvement in organ dysfunction following inflammatory adsorption therapy with Jafron HA 330 with a mean reduction in SOFA score of approximately 3.5 points at 72 hours.
A between-group difference of 2.5 SOFA points was considered clinically meaningful for both Endotoxin hemoadsorption and inflammatory mediators hemoadsorption because it represents a substantial proportion of the treatment effect observed in previous hemoperfusion studies and corresponds to a clinically relevant difference in the degree of organ dysfunction improvement.
The sample size for both groups (LPS and inflammatory mediator adsorption) was calculated based on the following assumption: the primary endpoint was the change in SOFA score at 72 hours (ΔSOFA); the expected between-group difference - 2.5 points on the SOFA score; standard deviation of ΔSOFA - 2.5 points; equal allocation ratio (1:1); two-sided significance level (α) of 0.05; statistical power of 80%.
Sample size estimation was performed in R using the power.t.test() function. The calculation yielded a required sample size of 16.7 participants per group. Therefore, a minimum of 17 participants per group (34 participants in total) is required to achieve the planned statistical power.
To account for an anticipated 10% dropout rate, the final sample size will be 19 patients per group (38 participants in total for LPS+ 38 participants in total for Inflammatory mediators adsorption. 76 participants in total).
Tipo de estudio
Inscripción (Estimado)
Fase
- No aplica
Contactos y Ubicaciones
Estudio Contacto
- Nombre: Aleksandr Burov, PHD
- Número de teléfono: +79854215478
- Correo electrónico: Aleksander.bour@mail.ru
Ubicaciones de estudio
-
-
-
Moscow, Rusia
- Petrovsky National Research Centre of Surgery
-
Contacto:
- Maxim Babaev, MD, PHD
- Número de teléfono: +79160269066
- Correo electrónico: maxbabaev@mail.ru
-
Moscow, Rusia
- Bakulev Scientific Center of Cardiovascular Surgery
-
Contacto:
- Mikhail Yarustovskiy, MD, PHD
- Número de teléfono: +79104194682
- Correo electrónico: mbyar@yandex.ru
-
Moscow, Rusia
- City clinical hospital named after S. S. Yudin, Moscow City Health
-
Contacto:
- Nikolay Krotenko, PHD
- Número de teléfono: +79268664976
- Correo electrónico: npkrotenko@gmail.com
-
Moscow, Rusia
- City Clinical Hospital No 52, Moscow, Russia
-
Contacto:
- Rustam Iskhakov
- Número de teléfono: +79265317813
- Correo electrónico: stamius@yandex.ru
-
Moscow, Rusia
- Moscow Multi-disciplinary Clinical Center "Kommunarka"
-
Moscow, Rusia
- Sklifosovsky Institute of Emergency Care
-
Contacto:
- Sergei Rei, PHD
- Número de teléfono: +79166001362
- Correo electrónico: reysi@sklif.mos.ru
-
Rostov-on-Don, Rusia
- National Medical Research Centre for Oncology Rostov-on-Don
-
Contacto:
- Natalia Ushakova, MD, PHD
- Número de teléfono: +79185533155
- Correo electrónico: ndu2000@rambler.ru
-
-
Criterios de participación
Criterio de elegibilidad
Edades elegibles para estudiar
- Adulto
- Adulto Mayor
Acepta Voluntarios Saludables
Descripción
Inclusion Criteria:
- Septic shock according to SEPSIS-3 criteria
- Age: 18-80 years
- SOFA ≥9 points
- Diagnosis of septic shock established <12 hours ago
- Invasive hemodynamic monitoring
- Norepinephrine dose >0.2 mcg/kg/min
Exclusion Criteria:
- Absolute neutrophil count less than 500 cells/μL
- Pregnancy
- End-stage heart failure (NYHA stage IV)
- Pulmonary embolism with obstructive shock
- Ongoing bleeding
- Atonic coma
- More than 30 points on the MELD scale, class C on the Child-Pugh scale
- HIV infection
- Burns over 10% of the body surface area
- Patients with oncohematological diseases
- Patients with a recognized palliative status or the definition of "metastatic cancer"
- RRT using membranes with a high cutoff point and increased adsorption capacity within 72 hours from the initiation of the first hemoadsorption procedure
- Use of plasma exchange within 72 hours from the initiation of the first hemoadsorption procedure
Plan de estudios
¿Cómo está diseñado el estudio?
Detalles de diseño
- Propósito principal: Tratamiento
- Asignación: Aleatorizado
- Modelo Intervencionista: Asignación paralela
- Enmascaramiento: Doble
Armas e Intervenciones
Grupo de participantes/brazo |
Intervención / Tratamiento |
|---|---|
|
Experimental: Inflammatory mediatiors adsorption with CytoSorb
Inflammatory mediatiors adsorption with EAA <0,6 with CytoSorb
|
Blood purification with Jafron HA 330
|
|
Comparador activo: Inflammatory mediatiors adsorption with Jafron HA 330
Inflammatory mediatiors adsorption with EAA <0,6 with Jafron HA 330
|
Blood purification with Jafron HA 330
|
|
Experimental: Endotoxin haemoadsorption with Toramyxin PMX 20R
Endotoxin haemoadsorption with EAA [0.6-0.9] with Toramyxin PMX 20R
|
Blood purification with Toramyxin PMX 20R
|
|
Comparador activo: Endotoxin haemoadsorption with Efferon LPS
Endotoxin haemoadsorption with EAA [0.6-0.9] with Efferon LPS
|
Blood purification with Efferon LPS
|
¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
|
SOFA (sequential organ failure assessment) score
Periodo de tiempo: Assessed at 72 hours after hemoadsorption initiation
|
MODS (multiple organ disfunction syndrome) dynamics majored by SOFA (sequential organ failure assessment) score.
SOFA score ranges from 0 (best) to 24 (worst) points.
|
Assessed at 72 hours after hemoadsorption initiation
|
Medidas de resultado secundarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
|
Lactate level dynamics
Periodo de tiempo: Assessed at 4 time points: before hemoadsorption initiation (baseline); 24 hours, 48 hours and 72 hours after hemoadsorption initiation
|
Lactate level dynamics (mmol/l)
|
Assessed at 4 time points: before hemoadsorption initiation (baseline); 24 hours, 48 hours and 72 hours after hemoadsorption initiation
|
|
Total bilirubin level dynamics
Periodo de tiempo: Assessed at 4 time points: before hemoadsorption initiation (baseline); 24 hours, 48 hours and 72 hours after hemoadsorption initiation
|
Total bilirubin level dynamics (mcmol/l)
|
Assessed at 4 time points: before hemoadsorption initiation (baseline); 24 hours, 48 hours and 72 hours after hemoadsorption initiation
|
|
Indirect bilirubin level dynamics
Periodo de tiempo: Time Frame: Assessed at 4 time points: before hemoadsorption initiation (baseline); 24 hours, 48 hours and 72 hours after hemoadsorption initiation
|
Indirect bilirubin level dynamics (mcmol/l)
|
Time Frame: Assessed at 4 time points: before hemoadsorption initiation (baseline); 24 hours, 48 hours and 72 hours after hemoadsorption initiation
|
|
Direct bilirubin level dynamics
Periodo de tiempo: Time Frame: Assessed at 4 time points: before hemoadsorption initiation (baseline); 24 hours, 48 hours and 72 hours after hemoadsorption initiation
|
Direct bilirubin level dynamics (mcmol/l)
|
Time Frame: Assessed at 4 time points: before hemoadsorption initiation (baseline); 24 hours, 48 hours and 72 hours after hemoadsorption initiation
|
|
Ferritin level dynamics
Periodo de tiempo: Time Frame: Assessed at 4 time points: before hemoadsorption initiation (baseline); 24 hours, 48 hours and 72 hours after hemoadsorption initiation
|
Ferritin level dynamics (mcg/l)
|
Time Frame: Assessed at 4 time points: before hemoadsorption initiation (baseline); 24 hours, 48 hours and 72 hours after hemoadsorption initiation
|
|
28 - days mortality
Periodo de tiempo: Will be calculated for 28 days after hemoadsorption initiation
|
28 - days mortality
|
Will be calculated for 28 days after hemoadsorption initiation
|
|
90 - days mortality
Periodo de tiempo: Will be calculated for 90 days after hemoadsorption initiation
|
90 - days mortality
|
Will be calculated for 90 days after hemoadsorption initiation
|
|
Vasoactive Inotropic Score (VIS) dynamics
Periodo de tiempo: Assessed at 4 time points: before hemoadsorption initiation (baseline); 24 hours, 48 hours and 72 hours after hemoadsorption initiation
|
Vasoactive Inotropic Score (VIS) dynamics VIS = dopamine dose (mcg∕kg∕ min ) + dobutamine dose (mcg∕kg∕ min ) + 100 × epinephrine dose (mcg∕kg∕ min ) + 10 × milrinone dose (mcg∕kg∕ min ) + 10,000 × vasopressin dose (units∕kg∕ min ) + 100 × norepinephrine dose (mcg∕kg∕ min ) |
Assessed at 4 time points: before hemoadsorption initiation (baseline); 24 hours, 48 hours and 72 hours after hemoadsorption initiation
|
|
Norepinephrine dose dynamics
Periodo de tiempo: Assessed at 4 time points: before hemoadsorption initiation (baseline); 24 hours, 48 hours and 72 hours after hemoadsorption initiation
|
Norepinephrine dose dynamics (mcg/kg/min)
|
Assessed at 4 time points: before hemoadsorption initiation (baseline); 24 hours, 48 hours and 72 hours after hemoadsorption initiation
|
|
Hemodynamic index dynamics
Periodo de tiempo: Assessed at 4 time points: before hemoadsorption initiation (baseline); 24 hours, 48 hours and 72 hours after hemoadsorption initiation
|
Hemodynamic index: Mean arterial pressure (MAP) to Vasoactive Inotropic Score (VIS); VIS = dopamine dose (mcg∕kg∕ min ) + dobutamine dose (mcg∕kg∕ min ) + 100 × epinephrine dose (mcg∕kg∕ min ) + 10 × milrinone dose (mcg∕kg∕ min ) + 10,000 × vasopressin dose (units∕kg∕ min ) + 100 × norepinephrine dose (mcg∕kg∕ min ) |
Assessed at 4 time points: before hemoadsorption initiation (baseline); 24 hours, 48 hours and 72 hours after hemoadsorption initiation
|
|
Horowitz index dynamics
Periodo de tiempo: Assessed at 4 time points: before hemoadsorption initiation (baseline); 24 hours, 48 hours and 72 hours after hemoadsorption initiation
|
Arterial oxygen partial pressure (PaO2)/fraction of inspired oxygen (FiO2) ratio (Horowitz index) dynamics
|
Assessed at 4 time points: before hemoadsorption initiation (baseline); 24 hours, 48 hours and 72 hours after hemoadsorption initiation
|
|
Procalcitonin (PCT) level dynamics
Periodo de tiempo: Time Frame: Assessed at 4 time points: before hemoadsorption initiation (baseline); 24 hours, 48 hours and 72 hours after hemoadsorption initiation
|
Procalcitonin (PCT) level dynamics (ng/ml)
|
Time Frame: Assessed at 4 time points: before hemoadsorption initiation (baseline); 24 hours, 48 hours and 72 hours after hemoadsorption initiation
|
|
C- reactive protein (CRP) level dynamics
Periodo de tiempo: Time Frame: Assessed at 4 time points: before hemoadsorption initiation (baseline); 24 hours, 48 hours and 72 hours after hemoadsorption initiation
|
C- reactive protein (CRP) level dynamics (mg/l)
|
Time Frame: Assessed at 4 time points: before hemoadsorption initiation (baseline); 24 hours, 48 hours and 72 hours after hemoadsorption initiation
|
|
NLR (neutrophil-to-lymphocyte ratio) dynamics
Periodo de tiempo: Time Frame: Assessed at 4 time points: before hemoadsorption initiation (baseline); 24 hours, 48 hours and 72 hours after hemoadsorption initiation
|
NLR (neutrophil-to-lymphocyte ratio) dynamics
|
Time Frame: Assessed at 4 time points: before hemoadsorption initiation (baseline); 24 hours, 48 hours and 72 hours after hemoadsorption initiation
|
|
PLR (Platelet-to-lymphocyte ratio) dynamics
Periodo de tiempo: Assessed at 4 time points: before hemoadsorption initiation (baseline); 24 hours, 48 hours and 72 hours after hemoadsorption initiation
|
PLR (Platelet-to-lymphocyte ratio) dynamics
|
Assessed at 4 time points: before hemoadsorption initiation (baseline); 24 hours, 48 hours and 72 hours after hemoadsorption initiation
|
|
TNF (Tumor necrosis factor-alpha) level dynamics
Periodo de tiempo: Assessed at 3 time points: before hemoadsorption initiation (baseline); 48 hours and 72 hours after hemoadsorption initiation
|
TNF (Tumor necrosis factor-alpha) level dynamics (pg/ml)
|
Assessed at 3 time points: before hemoadsorption initiation (baseline); 48 hours and 72 hours after hemoadsorption initiation
|
|
IL 6 (Interleukin 6) level dynamics
Periodo de tiempo: Assessed at 3 time points: before hemoadsorption initiation (baseline); 48 hours and 72 hours after hemoadsorption initiation
|
IL 6 (Interleukin 6) level dynamics (pg/ml)
|
Assessed at 3 time points: before hemoadsorption initiation (baseline); 48 hours and 72 hours after hemoadsorption initiation
|
|
IL 10 (Interleukin 10) level dynamics
Periodo de tiempo: Time Frame: Assessed at 3 time points: before hemoadsorption initiation (baseline); 48 hours and 72 hours after hemoadsorption initiation
|
IL 10 (Interleukin 10) level dynamics (pg/ml)
|
Time Frame: Assessed at 3 time points: before hemoadsorption initiation (baseline); 48 hours and 72 hours after hemoadsorption initiation
|
|
SOFA (sequential organ failure assessment) dynamics
Periodo de tiempo: Assessed at 4 time points: before hemoadsorption initiatioin (baseline); at 24, 48 and 120 hours after hemoadsorption initiation
|
MODS (multiple organ disfunction syndrome) dynamics majored by SOFA (sequential organ failure assessment) score
|
Assessed at 4 time points: before hemoadsorption initiatioin (baseline); at 24, 48 and 120 hours after hemoadsorption initiation
|
|
SOFA 2 (sequential organ failure assessment) dynamics
Periodo de tiempo: Assessed at 5 time points: before hemoadsorption initiatioin (baseline); at 24, 48, 72 and 120 hours after hemoadsorption initiation
|
MODS (multiple organ disfunction syndrome) dynamics majored by SOFA 2 (sequential organ failure assessment) score
|
Assessed at 5 time points: before hemoadsorption initiatioin (baseline); at 24, 48, 72 and 120 hours after hemoadsorption initiation
|
Otras medidas de resultado
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
|
Ventilator-free days
Periodo de tiempo: Will be calculated for 28 days after hemoadsorption initiation
|
Ventilator-free days
|
Will be calculated for 28 days after hemoadsorption initiation
|
|
Vasopressor-free days
Periodo de tiempo: Will be calculated for 28 days after hemoadsorption initiation
|
Vasopressor-free days
|
Will be calculated for 28 days after hemoadsorption initiation
|
|
Dialysis-free days
Periodo de tiempo: Will be calculated for 28 days after hemoadsorption initiation
|
Dialysis-free days
|
Will be calculated for 28 days after hemoadsorption initiation
|
|
Hospital length of stay
Periodo de tiempo: Will be calculated for 28 days after hemoadsorption initiation
|
Hospital length of stay
|
Will be calculated for 28 days after hemoadsorption initiation
|
|
Intensive care unit (ICU) length of stay
Periodo de tiempo: Will be calculated for 28 days after hemoadsorption initiation
|
Intensive care unit (ICU) length of stay
|
Will be calculated for 28 days after hemoadsorption initiation
|
|
AEs (adverse events)
Periodo de tiempo: Serious AEs will be reported up to Day 28
|
The safety will be assessed by analysing the number of adverse events (AEs) where causal relationship with the intervention cannot be excluded, up until Day 28.
|
Serious AEs will be reported up to Day 28
|
Colaboradores e Investigadores
Colaboradores
Investigadores
- Director de estudio: Denis Protsenko, MD, PHD, Moscow Multi-disciplinary Clinical Center "Kommunarka"
Publicaciones y enlaces útiles
Publicaciones Generales
- Cruz DN, Antonelli M, Fumagalli R, Foltran F, Brienza N, Donati A, Malcangi V, Petrini F, Volta G, Bobbio Pallavicini FM, Rottoli F, Giunta F, Ronco C. Early use of polymyxin B hemoperfusion in abdominal septic shock: the EUPHAS randomized controlled trial. JAMA. 2009 Jun 17;301(23):2445-52. doi: 10.1001/jama.2009.856.
- Onuk S, Akin AK, Sari A, Gundogan K, Baskol G, Dogru K, Sungur M. The Clinical and Laboratory Efficacy of HA 330 Treatment Combined with Continuous Renal Replacement Therapy in Septic Shock Patients: A Case Series. Blood Purif. 2023;52(2):140-147. doi: 10.1159/000528150. Epub 2023 Jan 12.
- Mehta Y, Mehta C, Kumar A, George JV, Gupta A, Nanda S, Kochhar G, Raizada A. Experience with hemoadsorption (CytoSorb(R)) in the management of septic shock patients. World J Crit Care Med. 2020 Jan 31;9(1):1-12. doi: 10.5492/wjccm.v9.i1.1. eCollection 2020 Jan 31.
- Rey S, Kulabukhov VM, Popov A, Nikitina O, Berdnikov G, Magomedov M, Kim T, Masolitin S, Ignatenko O, Krotenko N, Marysheva A, Chaus N, Ohinko L, Mendibaev M, Chumachenko A, Pisarev V. HEMOPERFUSION USING THE LPS-SELECTIVE MESOPOROUS POLYMERIC ADSORBENT IN SEPTIC SHOCK: A MULTICENTER RANDOMIZED CLINICAL TRIAL. Shock. 2023 Jun 1;59(6):846-854. doi: 10.1097/SHK.0000000000002121. Epub 2023 Apr 6.
- Klein DJ, Foster D, Walker PM, Bagshaw SM, Mekonnen H, Antonelli M. Polymyxin B hemoperfusion in endotoxemic septic shock patients without extreme endotoxemia: a post hoc analysis of the EUPHRATES trial. Intensive Care Med. 2018 Dec;44(12):2205-2212. doi: 10.1007/s00134-018-5463-7. Epub 2018 Nov 23.
Fechas de registro del estudio
Fechas importantes del estudio
Inicio del estudio (Estimado)
Finalización primaria (Estimado)
Finalización del estudio (Estimado)
Fechas de registro del estudio
Enviado por primera vez
Primero enviado que cumplió con los criterios de control de calidad
Publicado por primera vez (Actual)
Actualizaciones de registros de estudio
Última actualización publicada (Actual)
Última actualización enviada que cumplió con los criterios de control de calidad
Última verificación
Más información
Términos relacionados con este estudio
Palabras clave
Términos MeSH relevantes adicionales
Otros números de identificación del estudio
- HAdSS
Plan de datos de participantes individuales (IPD)
¿Planea compartir datos de participantes individuales (IPD)?
Descripción del plan IPD
Marco de tiempo para compartir IPD
Criterios de acceso compartido de IPD
Tipo de información de apoyo para compartir IPD
- PROTOCOLO DE ESTUDIO
- SAVIA
- RSC
Información sobre medicamentos y dispositivos, documentos del estudio
Estudia un producto farmacéutico regulado por la FDA de EE. UU.
Estudia un producto de dispositivo regulado por la FDA de EE. UU.
Esta información se obtuvo directamente del sitio web clinicaltrials.gov sin cambios. Si tiene alguna solicitud para cambiar, eliminar o actualizar los detalles de su estudio, comuníquese con register@clinicaltrials.gov. Tan pronto como se implemente un cambio en clinicaltrials.gov, también se actualizará automáticamente en nuestro sitio web. .