MCO Membrane Efficiency in Septic Shock Patients

Study Overview
=================
Brief Summary
-----------------
This is a monocentre randomized pilot study. All patients received two consecutive RRT: CVVHD with MCO filter (Ultraflux® EMiC®2) and post-Continuous Veno-Venous Hemodiafiltration (CVVHDF) with HFF(AV1000S®) in a controlled randomized (1:1) blinded manner. Crossover randomized to sequence (A+B or B+A) for 48 h total without washout.

Detailed Description
-----------------
This is a monocentre randomized pilot study. All patients received CVVHD with MCO filter (Ultraflux® EMiC®2) and post-Continuous Veno-Venous Hemodiafiltration (CVVHDF) with HFF(AV1000S®) in a controlled randomized (1:1) blinded manner. Crossover randomized to sequence (A+B or B+A) for 48 h total without washout. The efficiency of the filters for small and middle molecules was compared in septic shock patients with AKI stage 3.

Official Title
-----------------
Randomized Blinded Controlled Pilot Study on Clinical Assessment of Continuous Hemodialysis With a High Molecular Flux Membrane

Conditions
-----------------
Septic Shock, Acute Kidney Injury

Intervention / Treatment
-----------------
* Device: Ultraflux® EMiC®2


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Age > 18 years; septic shock according to ACCP/SCCM criteria AKI KDIGO stage 3 clinical decision to begin citrate based-RRT for at least 48 hours Hb >= 9 g/dL Obtain the informed consent Exclusion Criteria: Pre-existing chronic renal insufficiency Weight > 125 kg Life expectancy <24 hr Declared do Not Resuscitate or Comfort Measures Platelets < 20 [10^3/ul] or active bleeding Pregnancy Contraindication to citrate

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: All patients received two consecutive RRT (MCO-CVVHD and HFF-CVVHDF); in a controlled randomized (1:1) blinded manner. Each RRT treatment lasted 24 hours Crossover randomized to sequence (A+B or B+A) for 48 h total without washout
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MCO-CVVHD<br>CVVHD with MCO filter for 24 hours | Device: Ultraflux® EMiC®2<br>* Ultraflux® EMiC®2-CVVHD runs in septic shock patients with AKI KDIGO 3 for 24 hours. and patients were randomised to start Ultraflux® EMiC®2-CVVHD in the first day or in the second day from the RRT start; more precisely, crossover randomized to sequence consists in Ultraflux® EMiC®2-CVVHD (first day)+ HFF-CVVHDF(second day) and HFF-CVVHDF (first day) + Ultraflux® EMiC®2-CVVHD (second day) for 48 h total without washout<br>* Other names: HFF-CVVHDF;|
| Active Comparator: HFF-CVVHDF<br>CVVHDF with high flux filter for 24 hours | Device: Ultraflux® EMiC®2<br>* Ultraflux® EMiC®2-CVVHD runs in septic shock patients with AKI KDIGO 3 for 24 hours. and patients were randomised to start Ultraflux® EMiC®2-CVVHD in the first day or in the second day from the RRT start; more precisely, crossover randomized to sequence consists in Ultraflux® EMiC®2-CVVHD (first day)+ HFF-CVVHDF(second day) and HFF-CVVHDF (first day) + Ultraflux® EMiC®2-CVVHD (second day) for 48 h total without washout<br>* Other names: HFF-CVVHDF;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| improvement in haemodynamic parameters | measurements of the hemodynamic parameters: mean arterial pressure (MAP, mmHg) | 48 hours | 
| improvement in haemodynamic parameters | measurements of the hemodynamic parameters: heart rate (HR, beat/min) | 48 hours | 
| improvement in haemodynamic parameters | measurements of the hemodynamic parameters: lactate level (mmol/L) | 48 hours | 
| improvement in haemodynamic parameters | measurements of the hemodynamic parameters: cardiac index (CI; L/min/m2) | 48 hours | 
| improvement in haemodynamic parameters | measurements of the hemodynamic parameters: stroke volume variation (SVV; %) | 48 hours | 
| improvement in haemodynamic parameters | measurements of the hemodynamic parameters: PVC (mmHg) | 48 hours | 
| improvement in haemodynamic parameters | measurements of the hemodynamic parameters: SVRI (dyn*s/cm5*m2) | 48 hours | 
| improvement in haemodynamic parameters | measurements of the hemodynamic parameters: SCVO2 (%) | 48 hours | 
| improvement in haemodynamic parameters | measurements of the hemodynamic parameters: dose of vasopressor or inotropes (mcg/kg/min) | 48 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| clerance of cytokine | removal of IL-6 (pg/mL) | 48 hours | 
| clerance of cytokine | removal of IL-10 (pg/mL); reduction was evaluated after before and after the RRT | 48 hours | 
| clerance of cytokine | removal of IL-8 (pg/mL); reduction was evaluated after before and after the RRT | 48 hours | 
| clerance of cytokine | removal of MPO (U/L); reduction was evaluated after before and after the RRT | 48 hours | 
| Efficiency for middle molecules | measure of the efficacy (Kcd, (ml/kg/h)) of removal of B2microglobulin for each filter according to equation in Neri M, Villa G, Garzotto F, Bagshaw S, Bellomo R, Cerda J, Ferrari F, Guggia S, Joannidis M, Kellum J, Kim JC, Mehta RL, Ricci Z, Trevisani A, Marafon S, Clark WR, Vincent JL, Ronco C; Nomenclature Standardization Initiative (NSI) alliance. Nomenclature for renal replacement therapy in acute kidney injury: basic principles. Crit Care. 2016 Oct 10;20(1):318. Review. | 48 hours | 
| Efficiency for small molecules | measure of the efficacy (Kcd (ml/kg/h)) of BUN for each filter according to equation in Neri M, Villa G, Garzotto F, Bagshaw S, Bellomo R, Cerda J, Ferrari F, Guggia S, Joannidis M, Kellum J, Kim JC, Mehta RL, Ricci Z, Trevisani A, Marafon S, Clark WR, Vincent JL, Ronco C; Nomenclature Standardization Initiative (NSI) alliance. Nomenclature for renal replacement therapy in acute kidney injury: basic principles. Crit Care. 2016 Oct 10;20(1):318. Review. | 48 hours | 
| Efficiency for small molecules | measure of Efficacy (Kcd Cr (ml/kg/h)) of removal of SCr for each filter according to equation in Neri M, Villa G, Garzotto F, Bagshaw S, Bellomo R, Cerda J, Ferrari F, Guggia S, Joannidis M, Kellum J, Kim JC, Mehta RL, Ricci Z, Trevisani A, Marafon S, Clark WR, Vincent JL, Ronco C; Nomenclature Standardization Initiative (NSI) alliance. Nomenclature for renal replacement therapy in acute kidney injury: basic principles. Crit Care. 2016 Oct 10;20(1):318. Review. | 48 hours | 
| removal of antibiotics | evaluation of plasma level of vancomycin piperacillin/tazobactam(mcg/ml) | 48 hours | 
| removal of antibiotics | evaluation of plasma level of vancomycin (mcg/ml) | 48 hours | 
| removal of antibiotics | evaluation of plasma level of meropenem(mg/L) | 48 hours | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Renal Replacement Therapy,, Cytokines, Efficiency