Expanded Hemodialysis Versus Online Hemodiafiltration

NCT ID: NCT03274518

Last Updated: 2019-09-30

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 16 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-11-13
• Study Completion Date: 2019-03-11

Brief Summary

Conventional hemodialysis (HD) is essential for the treatment of end-stage renal disease (ESRD) patients, by reducing serum concentration of uremic toxins and correcting fluid overload.

Nevertheless, HD removes almost exclusively low-range uremic toxins. Therefore, medium-range molecules, such as beta-2-microglobulin might accumulate in tissues, leading to many clinical complications, such as neuropathies, tendinopathies, anemia, bone mineral disease and reduced growth in children.

Convective methods might reduce incidence of these complications, by removing molecules of medium-range molecular weight. Online hemodiafiltration (olHDF) is the most extensively used method in this regard. Nevertheless, there are some barriers to the wider introduction of this method in clinical practice, since specific machines are needed for this procedure, the costs with dialysis lines are higher and water consumption increases. More recently, the development of new membranes for hemodialysis allowed removal of medium- and high-range uremic toxins, with albumin retention. Thus, they allow removal of a broad range of uremic toxins, without changing dialysis machine or increasing water consumption. Such therapy is known as expanded hemodialysis (HDx).

The aim of this present study is to compare the extraction of middle-size molecules, the hemodynamic behavior, fluid and nutritional status of patients submitted to olHDF or HDx, in a crossover study.

Detailed Description

Hypothesis

Our hypothesis is that HDx is noninferior to olHDF in the following parameters:

• Hemodynamic stability
• Nutritional and fluid status
• Removal of beta-2 microglobulin

Objectives To evaluate each patient, through a prospective, randomized and cross-over study, the intradialytic hemodynamic behavior, fluid and nutritional status assessed by electrical bioimpedance and B2M removal in two dialytic modalities: HDFol versus HDx.

Concise methods

1. Clinical and laboratorial data Clinical data will be collected from the institution's chart, recorded and filled with all necessary precautions to keep confidentiality of patient's information. They are: baseline renal disease, age, history of smoking, sedentary lifestyle, presence of comorbidities such as hypertension and diabetes mellitus, family history of cardiovascular disease, history of coronary and cerebrovascular disease and medications.

Laboratory tests used to determine the biochemical, hematological and bone mineral profile characteristics will be obtained from routinely collected exams. Such exams are processed by the Central Laboratory of Hospital das Clínicas / FMUSP.

2. Dialysis All dialysis procedures will be performed by the Dialog+ Admea™ machine (BBraun Melsungen AG, Germany).

The olHDF will be prescribed as follows: blood flow 350 - 400 ml/min, dialysate flow 800 ml/min, post-dilution flow (90-100 ml/min), with high-flux Xevonta™ (BBraun Melsungen AG, Germany) or CAHP/DICE™ (Baxter Healthcare Corporation, Germany) dialyzers, with surface area of 1.7-2.4 m². The duration of each session will be from 3,5h to 4h, depending on current dialysis prescription. Total substitution volume will be higher than 20 L per session.

HDx will follow the same prescription of olHDF, regarding blood and dialysate flows and dialysis duration. There will be no substitution volume. Theranova™ dialyzers (Baxter Healthcare Corporation, Germany) will be used for each session.

Before initiating protocol and during the washout period, patients will be submitted to high-flux HD, which is the standard treatment in our service.

3. Hemodynamic monitoring Cardiac output index (CI), stroke volume (SV - integrated mean of the flow waveform between the current upstroke and the dichotic notch), peripheral arterial resistance (PAR - ratio of mean arterial pressure to stroke volume multiplied by heart rate) and blood pressure (BP) will be accessed by finger beat to-beat monitor Finometer™ (Finapress Medical Systems BV, Arnhem, The Netherlands), within 15 minutes after starting olHDF or HDx sessions (predialysis) and again, 15 minutes before its end (post-dialysis).

4. Bioelectrical impedance Segmental tetrapolar bioelectrical impedance (BIS) will be performed in all patients while recumbent, before starting study protocol and before each phase of the study (HDx or olHDF), by the multifrequency InBody™ S10 (Biospace Co., Ltd., Korea) device. It allows assessment of the following parameters regarding body fluids: total body water, total extracellular body water, lower limbs total water content, lower limbs extracellular water content. Additionally, α-angle, which is a marker of cellular integrity and nutritional status, will be noted.

5. Blood and Effluent samples Blood samples will be collected pre-session, mid-session and post-dialysis sessions, both in the first and last dialysis sessions of each of the periods studied (HDFol or HDx). Pre-session blood samples will be collected immediately after arteriovenous fistula puncture and the middle and post-session samples will be collected from the arterial line, 2 minutes after reduction of blood flow to 50 ml/min and suspension of dialysate flow and/ or replacement.

In addition, partial and homogeneous collection of the effluent will be performed by a drainage hose, with an infusion pump operating continuously at a rate of 1l/h. The whole effluent of dialysis session will be collected.

Conditions

Dialysis Related Complication; Dialysis Hypotension; Hemodialysis-Induced Symptom

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

Online Hemodiafiltration

The olHDF technique combines diffusion with high convection rates in which the dialysis fluid, free of toxins and pyrogens, is used to prepare the replacement fluid.

The online module of dialysis machine prepares the replacement fluid by a cold sterilization process. There is a cross-flow water preparation, in order to avoid the accumulation of possible contaminants. The addition of bicarbonate and acid solutions to water follows the process. Next, the ready-for-infusion dialysis solution is passed through another ultrafilter prior to being infused into patients.

Group Type: ACTIVE_COMPARATOR

Online Hemodiafiltration

Intervention Type: DEVICE

Intervention: Conversion from conventional HD to online Hemodiafiltration por 1 month.

Online hemodiafiltration has been associated with lower incidence of intradialytic hypotension in comparison to conventional hemodialysis.

Expanded Hemodialysis

More recently, membranes with high cutoff values, but with tight pore size distribution have been developed. The main concept is to keep both cutoff and retention onset values close to each other, but with a cutoff value lower than of albumin. This should allow removal of middle-to-high weight range uremic toxins, with very low albumin leak. Thus, these membranes, denominated high retention onset (HRO) membranes, allow performing both diffusive and convective processes in a conventional hemodialysis machine.

Group Type: EXPERIMENTAL

Expanded Hemodialysis

Intervention Type: DEVICE

Intervention: Conversion from conventional HD to expanded hemodialysis por 1 month.

High cutoff with high retention onset dialyzers allow clearance of middle molecules, without reducing significantly serum concentration of albumin. It allows higher convective clearance in comparison to conventional hemodialysis, but it is unknown if such clearance is similar to online hemodiafiltration. Therefore, the aim of the present intervention is to compare this dialyzer with online hemodiafiltration

Interventions

Expanded Hemodialysis

Intervention: Conversion from conventional HD to expanded hemodialysis por 1 month.

High cutoff with high retention onset dialyzers allow clearance of middle molecules, without reducing significantly serum concentration of albumin. It allows higher convective clearance in comparison to conventional hemodialysis, but it is unknown if such clearance is similar to online hemodiafiltration. Therefore, the aim of the present intervention is to compare this dialyzer with online hemodiafiltration

Intervention Type: DEVICE

Online Hemodiafiltration

Intervention: Conversion from conventional HD to online Hemodiafiltration por 1 month.

Online hemodiafiltration has been associated with lower incidence of intradialytic hypotension in comparison to conventional hemodialysis.

Intervention Type: DEVICE

Other Intervention Names

Theranova Dialyzer

Eligibility Criteria

Inclusion Criteria

• Adult patients who are on maintenance hemodialysis at Hospital das Clínicas and agree to participate in the study by signing the informed consent form.

Exclusion Criteria

• Patients who cannot understand or who refuse to sign the informed consent form; Patients who are currently on daily hemodialysis or online hemodiafiltration.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Sao Paulo

OTHER

Sponsor Role: lead

Responsible Party

Bruno Caldin da Silva

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Bruno C Silva, PhD

Role: PRINCIPAL_INVESTIGATOR

Renal Division, Unversity of São Paulo

Locations

Hospital das Clínicas

São Paulo, , Brazil

Countries

Brazil

References

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Reference Type: RESULT

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Reference Type: RESULT

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Silva BC, Moyses RM, Silva VB, Freitas GR, Elias RM. Parathyroidectomized patients have impaired capacity of peripheral vascular constriction during hemodialysis. Hemodial Int. 2016 Jan;20(1):50-5. doi: 10.1111/hdi.12309. Epub 2015 Apr 28.

Reference Type: RESULT

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Jimenez ZN, Silva BC, Reis LD, Castro MC, Ramos CD, Costa-Hong V, Bortolotto LA, Consolim-Colombo F, Dominguez WV, Oliveira IB, Moyses RM, Elias RM. High Dialysate Calcium Concentration May Cause More Sympathetic Stimulus During Hemodialysis. Kidney Blood Press Res. 2016;41(6):978-985. doi: 10.1159/000452601. Epub 2016 Dec 16.

Reference Type: RESULT

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Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

16928

Identifier Type: -

Identifier Source: org_study_id