Cytokine Removal With CVVHD Compared to CVVH

March 3, 2020 updated by: JOSE LUIS PEREZ FERNANDEZ, Hospital Universitari de Bellvitge

Cytokine Removal With CVVHD Using a Membrane With Adsorption Capacity: A Pilot Randomized Trial

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

Investigators will warrant a correct protocol application. Study data will be reviewed by an external monitoring committee from the clinical assay research central unit (UCICEC - IDIBELL). Monitors will contrast registered data from the collection data form (CDF) with data from patient´s medical record. All patient´s medical records will be indefinitely saved in electronical format to be reviewed if necessary. Participants who meet inclusion criteria will be randomized for one of both arms with aleatory assignation using a randomisation sequential (RndSeq) program for Statistical Package for the Social Sciences (SPSS). Investigators will report adverse events (in less than 24 hours if severe) to the sponsor center to be properly evaluated. If the severe adverse event (SAE) is finally evaluated by the study board as related to the intervention arm, urgent notification to health authorities must proceed and study should be interrupted until further decision. Data registry has been created to include all variables with written individual data collection forms (DCF). Data will be bedside registered by the investigators but final software database registration will be done by the statistics outside investigator who has no contact with the participant situation. Cytokines levels will be introduced in DCF when measured (every six months). Statistical analysis will be done by the statistics investigator who wont have any role in patient´s selection, randomization, or follow up. SPSS v. 18.0 for statistical analysis will be used. Variable distribution will be studied and logarithmic transformation will be used on those variables that don't present normal distribution, presumably cytokine levels. Univariate analysis comparing clinical, demographic, biochemical, metabolic, hemodynamic and respiratory baseline variables between both arms (CVVHD and CVVH), will be done with two-tailed t test for continuous variables and chi-square test for categorical variables. Variables determined several times (T0, T24, T48, T72) will be analysed using a one-way repeated measures ANOVA test in order to demonstrate differences between both arms. Multivariate analysis will be completed to control those clinically relevant confounding variables as well as to discover baseline differences. According to hypothesis and to the dependent variable on study, investigators will use a survival analysis (to study mortality) with a cox regression model, or a hierarchic multiple linear regression model when the dependent variable is continuous. Arm intervention (CVVHD, CVVH) will be considered as the main independent variable adding other control independent variables. As the study is measuring cytokine levels in five different moments (T0, T24, T48, T72), in order to maximize statistical power and reduce control variables number, the area under the curve (AUC) we´ll be determined for every cytokine during the first 72 hours. Due to this statistical maneuver, investigators will obtain a continuous variable that represents each cytokine level during the biochemical study period (72 hours). To evaluate if the arm intervention improvement in terms of efficacy and safety could be related to cytokine levels during the first 72 hours, a mediation complementary analysis will be done considering cytokine (represented by AUC) as a mediator between the independent variable (intervention arm) and the evaluated effect.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
40

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Spain
      • Barcelona, Spain
        • Hospital de la Santa Creu i Sant Pau
    • Barcelona
      • L'Hospitalet de Llobregat, Barcelona, Spain, 08907
        • Hospital Universitari de Bellvitge

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Less than 72 hours from ICU admission to inclusion
  • 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

Exclusion Criteria:

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Supportive Care
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: CVVHD with ST150
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
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.
Other Names:
  • Continuous venovenous hemodialysis
Active Comparator: CVVH with ST150
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
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.
Other Names:
  • Continuous venovenous haemofiltration

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Cytokine specific removal (0-72h)
Time Frame: 72 hours
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 Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Cardiovascular SOFA score variations.
Time Frame: 72 hours
Cardiovascular SOFA score will be registered every 24 hours (0-4) and variation from baseline to 72 hours will be evaluated calculating the Delta cardiovascular SOFA score from baseline to 72 h (SUM of the 4 daily SOFA scores).
72 hours
Respiratory SOFA score variations.
Time Frame: 72 hours
Respiratory SOFA score (0-4) will be registered every 24 hours and variation from baseline to 72 hours will be evaluated calculating the Delta respiratory SOFA score from baseline to 72 h (SUM of the 4 daily SOFA scores).
72 hours
Number of filters employed.
Time Frame: 72 hours
Number of times set was changed during the first 72 hours on CRRT.
72 hours
Rate of dialytrauma events
Time Frame: 72 hours
Rate of adverse events related to CRRT known as "dialytrauma". Red blood cells transfusions related with filter clotting, thrombocytopenia (less than 100.000), hypophosphatemia (less than 0.7 mmol/L), hypokaliemia (less than 3.3 mmol/ L), and hypothermia (less than 35.5ºC rectal temperature).
72 hours
Sieving coefficients for plasma solutes
Time Frame: 0-72 hours

Sieving coefficients for plasma solutes (creatinine, urea, potassium, albumine, magnesium, phosphate, and others) will be determined after measuring blood (pre and postfilter) and ultrafiltrate levels at 24 hours, 48 hours, and 72 hours.

24h, 48h, and 72h 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 20 - 28 hours for T24).
0-72 hours
Survival at 90 days after randomization
Time Frame: 90 days
Kaplan Meyer survival analysis and cox proportional hazard ratio for death will be both done at 90 days after CRRT initiation.
90 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Hospital Universitari de Bellvitge

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Chair: Jorge Ordoñez-Llanos, PhD, Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
March 13, 2013

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
November 1, 2015

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
March 1, 2016

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
February 13, 2019

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 5, 2019

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
August 7, 2019

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
March 5, 2020

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 3, 2020

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
August 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • CYTOHUB

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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