Efficacy of PEAF for Septic Shock With Multiple Organ Dysfunction Syndrome in ICU:A Multicenter,Open-Parallelled ,Randomized and Controlled Clinical Trial
Phase: NA
Conditions: Septic Shock, Multiple Organ Dysfunction Syndrome
Sponsor: Shenzhen Second People's Hospital

Study Protocol 
Efficacy of Therapeutic Plasma Exchange Adsorption Diafiltration(PEAF) 
for Septic Shock With Multiple Organ Dysfunction Syndrome in intensive care unit： 
A Multicenter,Open-Parallelled ,Randomized and Controlled Clinical Trial 
 
Original Protocol : May 18,2018 
 
Principal Investigator                          Ming Wu  MD  PhD 
 
Sponsor                           Shenzhen Second People's Hospital 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

Investigators and Institutional Review Board 
Principal Investigator 
Ming Wu  MD  PhD 
Other Investigators 
School of Public Health, Southern Medical University 
Guangzhou, Guang Dong, China, 510515 
  
Shengli Zhang, Ph.D  
  
   
Institutional Review Board 
The IRB 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

Background 
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 CPFA (coupled plasma-filtration adsorption) 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. 
Aims and Goals 
The current protocol is to evaluate the effect of Therapeutic Plasma Exchange Adsorption 
Diafiltration (PEAF) on Septic shock with multiple organ dysfunction syndrome (MODS). 
Setting and design 
This is a open-parallelled ,randomized and controlled clinical trial and the study is endorsed by 
Health and Family Planning Commission of Shenzhen Municipality and Shenzhen Second People's 
Hospital, and is approved by Medical ethics committee of Shenzhen No.2 People's Hospital.  
According to the mortality rate of patients with sepsis combined with MODS in our hospital for 
about one year is about 40%. The literature reported that the OR of coupled plasma-filtration 
adsorption(CPFA)treatment group was 0.36 (according to α=0.05, unilateral, 1−β=0.8; 
n=152(76×2)), according to statistical principles，The sample size calculated by PASS11.0 requires 
at least 152 cases, an increase of 10% of shedding cases. the total number of cases is at least 168 
subjects finally.   
 
Methods: 
The patients are considered registered once the informed consent form has been obtained by the 
patient or legal representative. The recruitment process ends with the patient center randomisation. 
Patients will be divided randomly into two arms (control and intervention). 
The characteristics of the groups are: Control group: Treatment following the suggestions provided 
by the recent surviving sepsis guidelines, as well as standard care guidelines typically followed in 
China. HVHF, High volume hemofiltration 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 
ACF180™ AsahiKASEI or AV1000S™ Fresenius）  
Intervention group: the patient is placed in the PEAF group, he/she will receive treatment with 
PEAF immediately after randomization. PEAF that is TPE (therapeutic plasma exchange 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 PFA (Blood pump: 120ml/min, 
Plasma separation rate 25-30%, plasma-filtration adsorption with Mediasorb™ BELLCO ITALY 

≥30ml/min) and HVPDF(High volume plasma diafiltration with ACF180™ AsahiKASEI or 
Ultraflux AV1000S™ Fresenius , 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. Same protocol with control group after 3days.  
The scheme of the trial is displayed in figure 1 and figure 2 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
   
 
 
 
 
Figure 1: Study diagram 
 
 
     
              PE 
PA+HVDF 
Figure 2: Pipeline connection  
 
 
Variables and measurements 
The primary outcome is all-cause mortality assessed at 28 days from the recruitment of the patient. 
First 6 hour since diagnosis,20≤APACHE II≤35 and 10≤SOFA≤18 
septic shock with multiple organ dysfunction syndrome 
Randomisation 
Control:HVHF(ACF180™ or 
AV1000S™ replacement and 
dialysate fluid 45ml/kg/min 
16 hours for 3 days) 
Intervention:TPE(PlamafloOP-08W 
20ml/kg/d1h)+PA(Mwdiasorb≥30ml/min)+
HVPDF(ACF180 or AV1000S replacement 
and dialysate fluid 2L/h 15h for 3 days) 
If hemodynamically unstable or AKI stage 2 or 3, continue HVHF 
Primary outcome: all-cause mortality within 28 days 
Secondary Outcome: all-cause mortality within 90 days and 
free hours of vasoactive drugs after randomization within 14 days 

Moreover, at the descriptive level and in order to check the homogeneity of both groups, the 
following variables will be collected at the time of recruitment: birth year, gender, height, dry weight, 
body temperature, heart rate, blood pressure, count blood cell, glucose level, plasma creatinine, 
bilirubinaemia, plasma C reactive protein, procalcitonin level, blood gas analysis, lactate, urinary 
output(mL/kg/hours), arterial oxygen tension/fractional inspired oxygen ratio, International 
Normalized 
Ratio(INR),Prothrombin 
time(second),activated 
partial 
thromboplastin 
time(second),Fibrinogen(g/L),D-Dimer(mg/L),Organ function(Acute Physiology and Chronic 
Health Evaluation II，Sequential Organ Failure Assessment，The Confusion Assessment Method 
for The Intensive Care Unit). 
Secondary Outcome: all-cause mortality within 90 days from randomization ,free hours of 
vasoactive drugs after randomization within 14 days.  
Finally, for all patients enrolled in the study, 10 ml of whole blood was taken from 8 am to 10 am 
every day, After centrifugation, the plasma was stored in a negative 80-degree refrigerator for 
subsequent follow-up testing.