Impact of CVVHD With Adsorption Capacity Membranes in Septic Acute Kidney Injury

July 25, 2019 updated by: Joan Sabater Riera, Hospital Universitari de Bellvitge

Impact of a Continuous Dialysis Technique Associated With Adsorption Capacity Membranes in Patients With Sepsis Associated - Acute Kidney Injury.

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 frequent complications, known as "dialytrauma", and a high resource cost both technical and human. The study primary end-point is to demonstrate a longer filter life with the use 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 less dialytrauma events of CVVHD respect to CVVH. In order to achieve these objectives investigators have designed a proof of concept exploratory trial that will include those patients 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 will also measure hemodynamic, respiratory, and metabolic parameters. Adverse effects related to CRRT ("dialytrauma") will also be registrated. Finally, investigators will analyze 90 days survival. Demonstration of a minor complication rate (longer filter patency with less dialytrauma events) with a similar immunomodulating capacity and with its consequent lower cost, should settle the based evidence principles that recommend the use of CVVHD asociated to an adsorption capacity membrane in patients with SA-AKI whom need CRRT.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Patients 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). Adverse events will be reported (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.

As a pilot study of at least 50 cases is advisable in many circumstances (Sim and Lewis, 2012), and we wanted to compare two treatment options, we aimed to recruit at least 100 patients.

Missing data will try to be avoided by an exhaustive patient´s follow up by study investigators. Intention to treat analysis (ITT) will be the main strategy and statistical substitution techniques for missing data will be applied when necessary. Per protocol analysis will also be done to avoid possible bias. Out-of-range results will be identified and processed with adequate statistical techniques.

Data registry has been created to include all variables with written individual data collection forms (DCF). Data will be bedside registered by the study members but final software database registration will be done by the statistics outside investigator who has no contact with patients 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-ST150 and CVVH-ST150), 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 (for example dialytrauma score). 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 and LPS 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 effect we study.

Data dictionary. ICU: Intensive Care Unit; AKI: Acute Kidney Injury; CRRT: Continuous Renal Replacement Therapies; IL-1β: interleukin 1β; TNF-α: tumor necrosis factor α; IL-6: interleukin 6, IL-10: interleukin 10; IL-4: interleukin 4; CVVH: Continuous Venovenous Hemofiltration; CVVHD: Continuous Venovenous Hemodialysis; SPSS: Statistical Package for the Social Sciences.

Study Type

Interventional

Enrollment (Actual)

110

Phase

  • 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, 08025
        • 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

Ages Eligible for Study

18 years to 85 years (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
  • Immunosuppression

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: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: CVVHD-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.
Other: 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-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.
Other: 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 reinfusion to maintain a theorical 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 hemofiltration

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Technical CRRT efficiency
Time Frame: 72 hours
Number of times set was changed.
72 hours

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Safety technical superiority.
Time Frame: 72 hours
Less 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
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.
Immunomodulating capacity
Time Frame: 72 hours

Cytokine removal: 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 (pre and postfilter) and in ultrafiltrate.

Determinations will be measured baseline (0hours), and at times 24hours, 48hours, and 72hours. 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).
72 hours
Renal depuration capacity.
Time Frame: 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 24hours, 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).
72 hours.
Hemodynamics and respiratory variations.
Time Frame: 72 hours.
Hemodynamic and respiratory parameters will be registered every hour. Arterial and venous gasometries with arterial lactate will be determined every 6 hours during the first 72 hours.
72 hours.
Clinical efficiency
Time Frame: 90 days
Days on CRRT. Days on Dialysis. Days of ICU. Days of hospital. Renal recovery at hospital discharge (free from dialysis).
90 days

Collaborators and Investigators

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

Sponsor

Hospital Universitari de Bellvitge

Collaborators

Hospital de Sant Pau

Investigators

  • Principal Investigator: Joan Sabater Riera, MD, Hospital Universitari de Bellvitge
  • Study Director: Xosé L. Pérez Fernández, MD, Hospital Universitari de Bellvitge
  • Study Director: Antoni Betbesé Roig, MD, Hospital de Sant Pau
  • Study Chair: Jorge Ordoñez Llanos, MD PhD, Hospital de Sant Pau

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

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)

May 1, 2013

Primary Completion (Actual)

August 1, 2017

Study Completion (Actual)

October 1, 2017

Study Registration Dates

First Submitted

February 8, 2013

First Submitted That Met QC Criteria

February 12, 2013

First Posted (Estimate)

February 13, 2013

Study Record Updates

Last Update Posted (Actual)

July 29, 2019

Last Update Submitted That Met QC Criteria

July 25, 2019

Last Verified

July 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • SIRAKI 00-2012
  • PR 148/12 (Other Identifier: Servei de Medicina Intensiva. HUB.)

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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