Efficacy of Uremic Toxins Clearance With Expanded Hemodialysis

NCT ID: NCT04786535

Last Updated: 2021-09-17

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

NA

Total Enrollment

23 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-05-10

Study Completion Date

2022-01-01

Brief Summary

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The aim of this study is to quantify the B2-microglobulin reduction rate based on the type of extracorporeal therapy (ET) used: HDx (expanded hemodialysis), HDc (high-flux conventional hemodialysis), or HDF (hemodiafiltration).

And to compare the magnitude of the B2-microglobulin reduction rate based on the type of extracorporeal therapy (ET) used: HDx, HDc, or HDF

Detailed Description

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A controlled, randomized, crossover clinical trial is planned to compare the magnitude of the B2-microglobulin reduction rate in three different extracorporeal therapies (ETs): HDc, HDx, and HDF.

The selection of study participants will be consecutive and for convenience

This study will be divided into six periods: three treatment periods (one for each therapy to be compared) and three of "washout" periods (interspersed between the treatment periods). The treatment periods will last four weeks (12 ET sessions, three per week) and will be preceded by a one-week washout period (three ET sessions)

After inclusion in the protocol, participants will be randomly assigned (with the help of a table of random numbers) to one of three ETs to be evaluated (HDc, HDx, or HDF). Afterwards, the first washout period will begin with high-flow conventional hemodialysis (HDc). At the end of the first washout period, the ET randomly assigned to one of three ETs to be evaluated (HDc, HDx, or HDF), following the sequence: Washout 1 -\> Period 1 (HDC, HDx, or HDF) -\> Washout 2 -\> Period 2, etc.

For each period of ET, there will be two sampling times: baseline and final

Blood samples will be obtained through the arterial port of the extracorporeal circuit, at the beginning and at the end of the ET session. The "slow flow" method will be used (UF: 0 mL/min, Qd: 0 mL/min, and Qb: 100 mL/min, for 30 seconds, before extracting the sample from the arterial port) (24). Blood samples will be collected in dry tubes (without anticoagulant) and centrifuged for 10 minutes at 3,000 RPM. The supernatant will be divided into three aliquots and stored at -70°C for further processing.

To calculate sample size, the formula for a noninferiority study was used (Pharmaceutical statistics. 2016;15(1):80-9), which is detailed below:

n= ((r+1) (Z\_(1-β)+Z\_(1-α) )\^2 σ\^2)/(r((μ\_A-μ\_B )-d\_NI )\^2 )

The terms above, are substituted with values obtained from the publication of Kirsch et al. (Nephrol Dial Transplant. 2017 Jan 1;32(1):165-172) as follows:

Objective: Non-inferiority (Ho µA - µB ≤ -dNI vs. µA - µB \> -dNI) Outcome: B2-microglobulin reduction rate. r: allocation ratio by group:1 beta: type II error (90% power):1.2816 alpha: type I error (level of significance 5%):1.960 (variance in the population):1.33 µA - µB (magnitude of the observed effect):80.6 - 78.5 = 2.1 dNI (non-inferiority limit): 3.5

n= ((1+1) (1.2816+1.960)\^2 〖(1.33)〗\^2)/(1((2.1)-3.5)\^2 )= 19, the investigators estimate a 20 % loss in the follow-up , then investigators consider a sample size of n = 23 patients

The nominal variables will be presented in frequencies and proportions. Continuous numerical variables will be analyzed using the Kolmogorov-Smirnov "Z" test to determine their distribution. The results will be shown as the means ± standard deviation in case of normal distribution and as a median with minimum and maximum limits for variables with non-normal distribution.

The total serum concentration of the biochemical variables in general as well as the uremic toxins will be analyzed. Additionally, the reduction rate and purification of the uremic toxins will be analyzed.

The analyses of the inter- and intra-group differences will be performed using the one-way multiple comparisons (ANOVA) method. Post hoc analysis using the Bonferroni method will be used in cases where the groups present a normal distribution; otherwise, the Kruskal-Wallis method will be used. A result with a p \< 0.05 will be considered significant

Conditions

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End Stage Renal Disease

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

CROSSOVER

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Hemodiafiltration

Group Type ACTIVE_COMPARATOR

Hemodiafiltration

Intervention Type PROCEDURE

* Single-use high-flux hemodialyzer
* Post-dilution mode
* Minimum convective volume of 23 L
* Blood flow (Qb) minimum of 300 mL/min
* Dialysis flow (Qd) 700 mL/min
* Minimum therapy time of 4 hours
* Ultrafiltration necessary to achieve dry weight

Expanded hemodialysis

Group Type EXPERIMENTAL

Expanded Hemodialysis

Intervention Type PROCEDURE

* Single-use Theranova 400 Dialyzer
* Blood flow (Qb) minimum of 300 mL/min
* Dialysis flow (Qd) 500 mL/min
* Minimum therapy time of 4 hours
* Ultrafiltration necessary to achieve dry weight

Conventional high-flux hemodialysis

Group Type EXPERIMENTAL

High-flux Conventional Hemodialysis

Intervention Type PROCEDURE

* Single-use high-flux hemodialyzer
* Blood flow (Qb) minimum of 300 mL/min
* Dialysis flow (Qd) 500 mL/min
* Minimum therapy time of 4 hours
* Ultrafiltration necessary to achieve dry weight

Interventions

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Expanded Hemodialysis

* Single-use Theranova 400 Dialyzer
* Blood flow (Qb) minimum of 300 mL/min
* Dialysis flow (Qd) 500 mL/min
* Minimum therapy time of 4 hours
* Ultrafiltration necessary to achieve dry weight

Intervention Type PROCEDURE

High-flux Conventional Hemodialysis

* Single-use high-flux hemodialyzer
* Blood flow (Qb) minimum of 300 mL/min
* Dialysis flow (Qd) 500 mL/min
* Minimum therapy time of 4 hours
* Ultrafiltration necessary to achieve dry weight

Intervention Type PROCEDURE

Hemodiafiltration

* Single-use high-flux hemodialyzer
* Post-dilution mode
* Minimum convective volume of 23 L
* Blood flow (Qb) minimum of 300 mL/min
* Dialysis flow (Qd) 700 mL/min
* Minimum therapy time of 4 hours
* Ultrafiltration necessary to achieve dry weight

Intervention Type PROCEDURE

Eligibility Criteria

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Inclusion Criteria

* Over 18 years
* Anuric patients (residual urinary volume ≤ 100 mL/24 h)
* Intermittent chronic hemodialysis (three sessions per week, of 3.5 to 4 hours each)
* Without modification of their prescription in the last three months
* Functional arteriovenous fistula, indwelling vascular access (Qb ≥ 300 mL/min), or both
* Letter of acceptance to enter the protocol and a signed informed consent.

Exclusion Criteria

* Under 18 years
* Active intake or intake in the last six months of immunosuppressants or systemic steroids
* Active autoimmune disease
* Evidence of active systemic infectious event at the time of inclusion or two weeks prior
* Diagnosis of neoplasia or active oncological disease
* Hypoalbuminemia (\< 3.2 g/dL)
* Pregnancy or lactation
* Refusal to participate in the study
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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Baxter México

UNKNOWN

Sponsor Role collaborator

Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Ricardo Correa-Rotter, MD

Role: PRINCIPAL_INVESTIGATOR

Head Departament of Nephrology and Mineral Metabolism,

Locations

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Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán

Mexico City, , Mexico

Site Status RECRUITING

Countries

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Mexico

Central Contacts

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Olynka Vega-Vega, MD

Role: CONTACT

+52 1 55 4803 9428

Ricardo Correa-Rotter, MD

Role: CONTACT

+52 1 55 7959 7066

Facility Contacts

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Olynka Vega-Vega, MD

Role: primary

+52 1 55 4803 9428

Ricardo Correa-Rotter, MD

Role: backup

+52 1 55 7959 7066

References

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Belmouaz M, Diolez J, Bauwens M, Duthe F, Ecotiere L, Desport E, Bridoux F. Comparison of hemodialysis with medium cut-off dialyzer and on-line hemodiafiltration on the removal of small and middle-sized molecules . Clin Nephrol. 2018 Jan;89 (2018)(1):50-56. doi: 10.5414/CN109133 .

Reference Type BACKGROUND
PMID: 28853700 (View on PubMed)

Ronco C. The Rise of Expanded Hemodialysis. Blood Purif. 2017;44(2):I-VIII. doi: 10.1159/000476012. Epub 2017 May 10.

Reference Type BACKGROUND
PMID: 28486230 (View on PubMed)

Ronco C, Marchionna N, Brendolan A, Neri M, Lorenzin A, Martinez Rueda AJ. Expanded haemodialysis: from operational mechanism to clinical results. Nephrol Dial Transplant. 2018 Oct 1;33(suppl_3):iii41-iii47. doi: 10.1093/ndt/gfy202.

Reference Type BACKGROUND
PMID: 30281134 (View on PubMed)

Zickler D, Schindler R, Willy K, Martus P, Pawlak M, Storr M, Hulko M, Boehler T, Glomb MA, Liehr K, Henning C, Templin M, Trojanowicz B, Ulrich C, Werner K, Fiedler R, Girndt M. Medium Cut-Off (MCO) Membranes Reduce Inflammation in Chronic Dialysis Patients-A Randomized Controlled Clinical Trial. PLoS One. 2017 Jan 13;12(1):e0169024. doi: 10.1371/journal.pone.0169024. eCollection 2017.

Reference Type BACKGROUND
PMID: 28085888 (View on PubMed)

Kirsch AH, Lyko R, Nilsson LG, Beck W, Amdahl M, Lechner P, Schneider A, Wanner C, Rosenkranz AR, Krieter DH. Performance of hemodialysis with novel medium cut-off dialyzers. Nephrol Dial Transplant. 2017 Jan 1;32(1):165-172. doi: 10.1093/ndt/gfw310.

Reference Type BACKGROUND
PMID: 27587605 (View on PubMed)

Other Identifiers

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REF.2937

Identifier Type: -

Identifier Source: org_study_id

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