Therapeutic Plasma Exchange Adsorption Diafiltration

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the efficacy of coupled therapeutic plasma exchange adsorption diafiltration (PEAF )for treating septic shock with multiple organ dysfunction syndrome patients in ICU.

Detailed Description
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Septic shock with multiple organ dysfunction syndrome (MODS) is a life-threatening clinical condition due to coagulant disorder immunoparalysis to infection. For this reason the extracorporeal therapies for the treatment of septic shock with MODS have become widespread in the ICU and, at the same time, new extracorporeal depurative techniques have been developed for the removal of inflammatory mediators. One of these techniques is therapeutic plasma exchange (TPE) that remove pathologically elevated cytokines and simultaneously to replace protective plasmatic factors. other techniques is coupled plasma-filtration adsorption (CPFA) that uses a sorbent once the separation between plasma and blood has been obtained with a plasma filter. The others is Plasma dialysis filtration(PDF) that can remove inflammatory mediators for patients with multiple organ dysfunction syndrome.The purpose of this study is to evaluate the efficacy of PEAF (coupled therapeutic plasma exchange adsorption diafiltration )for treating septic shock with multiple organ dysfunction syndrome patients in ICU.

Official Title
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Efficacy of PEAF for Septic Shock With Multiple Organ Dysfunction Syndrome in ICU:A Multicenter,Open-Parallelled ,Randomized and Controlled Clinical Trial

Conditions
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Septic Shock, Multiple Organ Dysfunction Syndrome

Intervention / Treatment
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* Procedure: PEAF


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age, gender: 18-75 years old, male or female; basic conditions: 20 ≤ APACHE II score ≤ 35 points and 10 ≤ Sequential Organ Failure Assessment(SOFA)≤ 18 points; septic shock : On the basis of sepsis, after adequate fluid resuscitation, sustained hypotension requires maintenance of vasoactive drugs, mean arterial pressure（MAP）≥ 60 mmHg and Lactate ≥ 2.0 mmol/L; MODS: if the patient's SOFA score is ≥2 points, it means there is organ dysfunction. When the patient has two or more organ dysfunctions, it is MODS. Exclusion Criteria: can not remove the cause (surgical patients refused surgery, pan drug resistant infection without drug use) Allergic to AMPLYA™ series Presence of relative or absolute contraindications to PFA MODS caused by severe liver disease malignant tumors Chronic end-stage disease (predicted to survive no more than one month) Maternal and possibly pregnant women participated in drug clinical trials within three months Admission from an other ICU where the patient remained for more than 24 hours

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: a Multicenter,Randomized and Controlled Clinical Trial
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PEAF<br>Intervention group:the patient will receive treatment with PEAF immediately after randomization.PEAF that is TPE (20ml/kg/d Fresh frozen plasma, Blood pump: 120ml/min, replacement pump 20ml/kg/min, dialysate pump 0ml/kg/min, waste pump 20ml/kg/min, plasma exchange 1 hour) plus plasma-filtration adsorption(PFA) (Blood pump: 120ml/min, Plasma separation rate 25-30%, PFA with acute multitherapeutic system (AMPLYA™ Italy) ≥30ml/min) and High volume plasma diafiltration (HVPDF) with CUREFLO™(ACF180W Japan) or Ultraflux® (AV1000S Fresenius Germany) , Blood pump same as PFA , replacement fluid pump 2000ml/h, dialysate pump 2000ml/h, waste pump 4000ml/h),with PFA and HVPDF for 15 hours in the first 3 days. If hemodynamically unstable or acute kidney injury(AKI) stage 2or 3,continue High volume hemofiltration(HVHF).Same protocol with control group after 3days. | Procedure: PEAF<br>* PEAF that is therapeutic plasma exchange (TPE) with 20ml/kg/d Fresh frozen plasma (Blood pump: 120ml/min, replacement pump 20ml/kg/min, dialysate pump 0ml/kg/min, waste pump 20ml/kg/min, plasma exchange 1 hour) plus plasma filtration adsorption (PFA ) with acute multitherapeutic system( AMPLYA™ ITALY) ≥30ml/min lasting 15 hours plus High volume plasma diafiltration (HVPDF) with CUREFLO™(ACF180W Japan) or Ultraflux® (AV1000S Fresenius Germany) Blood pump: 120ml/min, replacement fluid pump 2000ml/h, dialysate pump 2000ml/h, waste pump 4000ml/h,and with high-volume plasma diafiltration for 15 hours）in the first 3 days. the treatment after three days later is same as the control group.<br>|
| No Intervention: Control group<br>HVHF for septic shock with MODS is permitted in Control group routinely（Blood pump: 200ml/min, replacement fluid pump 45ml/kg/min, dialysate pump 45ml/kg/min, waste pump 90ml/kg/min, and high-volume hemofiltration for 16 hours with CUREFLO™(ACF180W Japan) or Ultraflux® (AV1000S Fresenius Germany) in the first 3 days after randomization.If hemodynamically unstable or AKI stage 2or 3,continue HVHF. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| All-cause mortality within 28 days after randomization | efficacy | 28 days after randomization | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| All-cause mortality within 90 days from randomization | efficacy | 90 days from randomization | 
| free hours of vasoactive drugs from randomization | efficacy | 14 days after randomization |