Cytokine Removal With CVVHD Compared to CVVH

NCT04048525 | Completed DMC

• 1 other identifier: CYTOHUB
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 2

Brief Summary

Septic patients with acute kidney injury (SA-AKI) requiring continuous renal replacement therapies (CRRT) present high mortality due to systemic inflammatory response, cytokine liberation, and finally multiorgan dysfunction. Cytokine plasmatic elimination with continuous venovenous hemofiltration (CVVH) presents a high resource cost both technical and human. The study primary end-point is to demonstrate a similar cytokine removal of continuous venovenous hemodialysis (CVVHD) respect to CVVH, both modalities employing the same adsorption capacity membrane. As secondary end-points investigators will try to demonstrate technical superiority of CVVHD respect to CVVH. In order to achieve these objectives investigators have designed a proof of concept exploratory trial that will include those participants whom present SA-AKI meeting CRRT initiation criteria. During the first 72 hours investigators will measure plasmatic elimination capacity of main cytokines, and other clinical and prognostic relevant molecules. Investigators wil measure mean filter life during all CRRT with special attention to the first 72 hours. Investigators will also measure hemodynamic, respiratory, and metabolic parameters. Finally, investigators will analyze 90 days survival. Demonstration of a similar immunomodulating capacity and a minor complication rate with its consequent lower cost, should settle the based evidence principles that recommend the use of CVVHD associated to an adsorption capacity membrane in patients with SA-AKI whom need CRRT.

Conditions

Cytokine Release Syndrome; Sepsis; AKI

Keywords

CRRT; CVVHD; CVVH

Outcome Measures

Primary Outcomes (1)

• Cytokine specific removal (0-72h)

  Cytokine concentration changes between baseline and 72 hours for each cytokine: interleukin-1β (IL-1β), tumor necrosis factor α (TNF-α), interleukin 6 (IL-6), interleukin-4 (IL-4), and interleukin-10 (IL-10) levels will be determined in plasma. Changes will be expressed in percentages respect to baseline concentrations for each cytokine. Determinations should only be done when ST150 set has been working for at least 6 continuous hours. This means that determinations can be advanced or delayed +/- 4 hours to scheduled time (for example 68 - 76 hours for T72).

  72 hours

Secondary Outcomes (6)

• Cardiovascular SOFA score variations.

  72 hours

• Respiratory SOFA score variations.

  72 hours

• Number of filters employed.

  72 hours

• Rate of dialytrauma events

  72 hours

• Sieving coefficients for plasma solutes

  0-72 hours

Study Arms (2)

CVVHD with ST150

EXPERIMENTAL

Patients with sepsis whom present AKI meeting CRRT initiation criteria will be started on CVVHD with PrismafleX eXeed™ II (Hospal) using an ST150SET copolymer of acrylonitrile and sodium methylsulfonate (AN 69) with polyethylenimine treated surface. Anticoagulation of the ST150 set with unfractioned heparin will only be initiated if there´s no clinical contraindication. ST150 set will be changed when clotted and every 24 hours during the first 72 hours of CVVHD. No citrate anticoagulation will be used.

Procedure: CVVHD

CVVH with ST150

ACTIVE COMPARATOR

Patients with sepsis whom present AKI meeting CRRT initiation criteria will be started on CVVH with PrismafleX eXeed™ II (Hospal) using an ST150SET copolymer of acrylonitrile and sodium methylsulfonate (AN 69) with polyethylenimine treated surface. Anticoagulation of the ST150 set with unfractioned heparin will only be initiated if there´s no clinical contraindication. ST150 set will be changed when clotted and every 24 hours during the first 72 hours of CVVH. No citrate anticoagulation will be used.

Procedure: CVVH

Interventions

CVVHD PROCEDURE

CVVHD will be used during 72 hours with a prescribed dose of 30 ml/Kg/h Prismasol® 4 as dialysate fluid. Blood flow of 200-250 ml/min, to achieve 12 - 15 L/h will be prescribed. Isovolemic CRRT will be encouraged during this 72 hours if volume overload status is not present. After 72 hours, CVVHD will be continued and dialysate dose (ml/kg/h) will be adjusted to achieve creatinine levels between 80-120 umol/L until patient recovers urine output and / or tolerates intermittent hemodialysis.

Also known as: Continuous venovenous hemodialysis

CVVHD with ST150

CVVH PROCEDURE

CVVH will be used during 72 hours with a prescribed dose of 30 ml/Kg/h Prismasol® 4 as reposition fluid. Blood flow of 200-250 ml/min, to achieve 12 - 15 L/h will be prescribed adjusting the adequate percentage of prefilter infusion to maintain a theoretical filtration fraction between 18-22%. Isovolemic CRRT will be encouraged if volume overload status is not present. After 72 hours, CVVH will be continued and filtration dose (ml/kg/h) will be adjusted to achieve creatinine levels between 80-120 umol/L until patient recovers urine output and / or tolerates intermittent hemodialysis.

Also known as: Continuous venovenous haemofiltration

CVVH with ST150

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Clinical diagnosis of Severe Sepsis or Septic shock (SCCM definitions)
• Correct therapeutic initial management of septic process (SSC guidelines)
• Clinical diagnosis of Acute Kidney Injury (ADQI definitions)
• Acute Kidney Injury meeting CRRT initiation criteria (ADQI guidelines)
• Written informed consent from patient or legal surrogates

You may not qualify if:

• End Stage Renal Disease(ESRD)
• Received previous CRRT or hemodialysis in the last three months
• Coexisting illness with a high probability of death

Sponsors & Collaborators

• Hospital Universitari de Bellvitge: lead
• Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau: collaborator

Study Sites (2)

Hospital Universitari de Bellvitge

L'Hospitalet de Llobregat, Barcelona, 08907, Spain

Location

Hospital de la Santa Creu i Sant Pau

Barcelona, Spain

Location

MeSH Terms

Conditions

Cytokine Release Syndrome; Sepsis

Interventions

Continuous Renal Replacement Therapy

Condition Hierarchy (Ancestors)

Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Shock; Infections

Intervention Hierarchy (Ancestors)

Renal Replacement Therapy; Therapeutics; Extracorporeal Circulation; Surgical Procedures, Operative

Study Officials

• Jorge Ordoñez-Llanos, PhD

  Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: SUPPORTIVE CARE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: Pilot randomized controlled trial

Study Record Dates

• First Submitted: February 13, 2019
• First Posted: August 7, 2019
• Study Start: March 13, 2013
• Primary Completion: November 1, 2015
• Study Completion: March 1, 2016
• Last Updated: March 5, 2020

Record last verified: 2019-08

Data Sharing

• IPD Sharing: Will not share

Locations

ES (2)