CClinicalTrials.gg
CompletedNCT03274518Updated Sep 30, 2019Results posted

Expanded Hemodialysis Versus Online Hemodiafiltration

An interventional study of Expanded Hemodialysis and Online Hemodiafiltration in Dialysis Related Complication, Dialysis Hypotension and Hemodialysis-Induced Symptom, sponsored by University of Sao Paulo. Completed at 1 site in Brazil. Open to participants aged 18 Years to 65 Years. Per ClinicalTrials.gov, last updated 2019-09-30.

Sponsored by University of Sao Paulo · Not applicable, Interventional, and Treatment

Phase
Not applicable
Study type
Interventional
Enrollment
16
Allocation
Randomized
Ages
18 Years to 65 Years
Sex
All
01

Study 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.

Read the 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.

02

Conditions studied

  • Dialysis Related Complication
  • Dialysis Hypotension
  • Hemodialysis-Induced Symptom

Browse trials for

Keywords

  • Hemodialysis
  • Hemodiafiltration
  • fluid status
  • hemodynamics
03

Who can participate

Ages eligible
18 Years to 65 Years
Sexes eligible
All
Accepts healthy volunteers
No

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

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.
04

Study design

Phase
Not applicable
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Crossover assignment
Masking
Single (Investigator)
Enrollment
16 participants (actual)

Study arms

  • Active comparator
    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.

    Device: Online Hemodiafiltration

  • Experimental
    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.

    Device: Expanded Hemodialysis

Interventions

  • DeviceExpanded 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

    Also known as: Theranova Dialyzer

  • DeviceOnline 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.

05

What researchers measure

Primary outcomes

  1. Medium Molecule Clearance

    Beta-2-Microglobulin clearance

    Time frame: One month after starting protocol

  2. Medium Molecule Removal

    Beta-2-Microglobulin extraction

    Time frame: One month after starting protocol

Secondary outcomes

  1. Intradialytic Hemodynamics

    noninvasive cardiac output assessment

    Time frame: Cardiac output (liters per minute) one month after starting protocol

Other outcomes

  1. Fluid Status

    noninvasive assessment of extracellular and total body water

    Time frame: One month after starting protocol

06

Results

Posted Sep 30, 2019
Limitations and caveats
The sample size was small and trial length was relatively short. We did not directly assessed albumin extraction. Besides, the relatively low ultrafiltration coefficient of both dialyzers limited dialysis performance in all treatment groups.

Participant flow

First Intervention
Participant flow — First Intervention
MilestoneOnline HemodiafiltrationExpanded Hemodialysis
Started88
Completed88
Not completed00
Washout Period
Participant flow — Washout Period
MilestoneOnline HemodiafiltrationExpanded Hemodialysis
Started88
Completed88
Not completed00
Second Intervention
Participant flow — Second Intervention
MilestoneOnline HemodiafiltrationExpanded Hemodialysis
Started88
Completed88
Not completed00

Outcome measures

PrimaryMedium Molecule Clearance

Beta-2-Microglobulin clearance

Time frame:
One month after starting protocol
Reported as:
Median · ml/min
Medium Molecule Clearance
ml/minOnline HemodiafiltrationExpanded Hemodialysis
Medium Molecule Clearance53 (41.8 to 63.7)59.5 (50.5 to 70)
Statistical analysis
  • Online Hemodiafiltration vs Expanded Hemodialysis · t-test, 2 sided · p = 0.4534
PrimaryMedium Molecule Removal

Beta-2-Microglobulin extraction

Time frame:
One month after starting protocol
Reported as:
Mean · mg
Medium Molecule Removal
mgOnline HemodiafiltrationExpanded Hemodialysis
Medium Molecule Removal198 ± 81239 ± 86
Statistical analysis
  • Online Hemodiafiltration vs Expanded Hemodialysis · t-test, 2 sided · p = 0.1179
SecondaryIntradialytic Hemodynamics

noninvasive cardiac output assessment

Time frame:
Cardiac output (liters per minute) one month after starting protocol
Reported as:
Median · l/min
Intradialytic Hemodynamics
l/minOnline HemodiafiltrationExpanded Hemodialysis
Intradialytic Hemodynamics-1.3 (-2.2 to -0.3)-1.4 (-3 to -1.1)
Statistical analysis
  • Online Hemodiafiltration vs Expanded Hemodialysis · t-test, 2 sided · p = 0.3054
Other pre-specifiedFluid Status

noninvasive assessment of extracellular and total body water

Time frame:
One month after starting protocol
Reported as:
Mean · liter/liter
Fluid Status
liter/literOnline HemodiafiltrationExpanded Hemodialysis
Fluid Status0.39 ± 0.010.385 ± 0.01
Statistical analysis
  • Online Hemodiafiltration vs Expanded Hemodialysis · t-test, 2 sided · p = 0.045

Adverse events

Collected over 3 months. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Online Hemodiafiltration0/8 (0%)0/8 (0%)0/8 (0%)
Expanded Hemodialysis0/8 (0%)0/8 (0%)0/8 (0%)

Baseline characteristics

Age, Categorical
Age, Categorical(Participants)Online HemodiafiltrationExpanded HemodialysisTotal
<=18 years000
Between 18 and 65 years7815
>=65 years101
Age, Continuous
Age, Continuous(years)Online HemodiafiltrationExpanded HemodialysisTotal
Median39.5 (28.7 to 43.5)46 (28.7 to 59.5)39.5 (28.7 to 52.2)
Sex: Female, Male
Sex: Female, Male(Participants)Online HemodiafiltrationExpanded HemodialysisTotal
Female325
Male5611
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)Online HemodiafiltrationExpanded HemodialysisTotal
Hispanic or Latino8715
Not Hispanic or Latino011
Unknown or Not Reported000
Region of Enrollment
Region of Enrollment(participants)Online HemodiafiltrationExpanded HemodialysisTotal
Brazil8816
Serum Beta-2 Microglobulin
Serum Beta-2 Microglobulin(mcg/ml)Online HemodiafiltrationExpanded HemodialysisTotal
Mean23.2 ± 6.927.8 ± 5.525.2 ± 6.1
07

Study locations

1 site
  • Hospital das Clínicas
    São Paulo, 05403-000, Brazil
08

References and documents

Publications

  • Karohl C, de Paiva Paschoal J, de Castro MC, Elias RM, Abensur H, Romao JE Jr, Passlick-Deetjen J, Jorgetti V, Moyses RM. Effects of bone remodelling on calcium mass transfer during haemodialysis. Nephrol Dial Transplant. 2010 Apr;25(4):1244-51. doi: 10.1093/ndt/gfp597. Epub 2010 Jan 29. PubMed 20118484 ↗
  • Cheng YL, Shek CC, Wong FK, Choi KS, Chau KF, Ing TS, Li CS. Determination of the solute removal index for urea by using a partial spent dialysate collection method. Am J Kidney Dis. 1998 Jun;31(6):986-90. doi: 10.1053/ajkd.1998.v31.pm9631843. Erratum In: Am J Kidney Dis 1998 Oct;32(4):704. PubMed 9631843 ↗
  • Alvares VRC, Ramos CD, Pereira BJ, Pinto AL, Moyses RMA, Gualano B, Elias RM. Pneumatic Compression, But Not Exercise, Can Avoid Intradialytic Hypotension: A Randomized Trial. Am J Nephrol. 2017;45(5):409-416. doi: 10.1159/000471513. Epub 2017 Apr 14. PubMed 28407637 ↗
  • Cheng YL, Shek CC, Wong AK, Wong FK, Chau KF, Li CS. A partial dialysate collection method. Int J Artif Organs. 1997 Jan;20(1):14-7. PubMed 9062826 ↗
  • Argiles A, Ficheux A, Thomas M, Bosc JY, Kerr PG, Lorho R, Flavier JL, Stec F, Adele C, Leblanc M, Garred LJ, Canaud B, Mion H, Mion CM. Precise quantification of dialysis using continuous sampling of spent dialysate and total dialysate volume measurement. Kidney Int. 1997 Aug;52(2):530-7. doi: 10.1038/ki.1997.364. PubMed 9264013 ↗
  • Oliveira CM, Kubrusly M, Mota RS, Silva CA, Choukroun G, Oliveira VN. The phase angle and mass body cell as markers of nutritional status in hemodialysis patients. J Ren Nutr. 2010 Sep;20(5):314-20. doi: 10.1053/j.jrn.2010.01.008. Epub 2010 Mar 19. PubMed 20303790 ↗
  • Silva BC, Freitas GR, Silva VB, Abensur H, Luders C, Pereira BJ, de Oliveira RB, Castro MC, Moyses RM, Elias RM. Hemodynamic behavior during hemodialysis: effects of dialysate concentrations of bicarbonate and potassium. Kidney Blood Press Res. 2014;39(5):490-6. doi: 10.1159/000368459. Epub 2014 Nov 23. PubMed 25532082 ↗
  • 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. PubMed 25923250 ↗
  • 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. PubMed 27978518 ↗

Study documents

  • Protocol and statistical analysis plan · Sep 27, 2019
  • Informed consent form · Oct 17, 2018

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: No

09

Registry details

Key details

Study ID
NCT03274518
Lead sponsor
University of Sao Paulo
Responsible party
Bruno Caldin da Silva (Principal Investigator, University of Sao Paulo) — Principal investigator
First posted
Sep 7, 2017
Start date
Nov 13, 2017
Primary completion
Oct 18, 2018
Completion
Mar 11, 2019
Results posted
Sep 30, 2019
Last update
Sep 30, 2019

Study contacts

Bruno C Silva, PhD
principal investigator · Renal Division, Unversity of São Paulo

Oversight

Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

Not currently enrolling

This study is completed, as verified in Sep 2019. You cannot join it, but the record below documents what was studied.

Follow this study

Get an email when the registry record changes — status, dates, results — or when someone posts here.

Sign in to follow

Discussion

Questions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.

Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.

Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.

Start the discussion