Condition category
Circulatory System
Date applied
18/06/2020
Date assigned
22/06/2020
Last edited
21/06/2020
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Background and study aims
Hemodialysis is a treatment for patients with end-stage kidney disease where blood is removed from the body (usually via blood vessels of the arm) and filtered through a machine, where products in the blood are exchanged with the dialysis fluid (dialysate) across a membrane, before being returned to the body. It is used to replace the loss of function of the kidneys, to filter wastes and water from the blood, to ensure that these do not build up. Hemodialysis helps to control blood pressure and balance important minerals in the blood.

Cardiovascular diseases are the most frequent cause of death in patients with end-stage kidney disease. Blood vessel stiffness, high blood pressure, and changes to the functioning of the lining of blood vessels are factors involved in the progress of cardiovascular disease in hemodialysis patients. It has previously been shown that using a higher concentration of magnesium in the dialysis fluid during dialysis sessions could reduce the rate at which blood vessel stiffness develops, and may improve the functioning of the lining of blood vessels.

The aim of this study is to examine whether increasing the concentration of magnesium in the dialysate from 0.50 mmol/L to 0.75 mmol/L could affect blood vessel stiffness, high blood pressure, and changes to the functioning of the lining of blood vessels in patients with end-stage kidney disease undergoing hemodialysis. The study also aims to investigate the long-term effect of increased magnesium concentration in the dialysate (to 0.75 mmol/L) on mineral metabolism markers over 6 months.

Who can participate?
All patients with end-stage kidney disease, aged more than 18 years, and undergoing regular hemodialysis will be eligible to participate, excluding critically ill patients and pregnant patients or patients at risk of pregnancy.

What does the study involve?
Participants are assigned to 2 weeks of treatment with either a concentration of magnesium in the dialysis fluid at 0.50 mmol/L or at 0.75 mmol/L. Then they will have 3 days with no hemodialysis, followed by 2 weeks of hemodialysis with the concentration of magnesium that they had not previously recived. At the end of the 4 weeks of treatment participants will be assessed for changes to the blood vessels and blood pressure.

After the 4 weeks of treatment, all participants who will be continuing hemodialysis will receive hemodialysis with a concentration of magnesium in the dialysis fluid of 0.75 mmol/L, as already planned for every patient by the internal guidelines of the network to whom the dialysis center of the study belongs. After a period of 6 months, long term-changes will be assessed.

What are the possible benefits and risks of participating?
It has previously been demonstrated that there could be an overall cardiovascular benefit in using a higher concentration of magnesium in the dialysis fluid. A possible risk is related to a high blood magnesium level causing low blood pressure. The risks of participating in this study are not anticipated to be greater than for routine hemodialysis treatment.

Where is the study run from?
Dialysis center of the Regional Hospital of Bellinzona and Valli (Switzerland)

When is the study starting and how long is it expected to run for?
May 2017 to August 2019

Who is funding the study?
Scientific Research Advisory Board (ABREOC) of the Ente Ospedaliero Cantonale (Switzerland)

Who is the main contact?
Prof. Luca Gabutti,
luca.gabutti@eoc.ch

Trial website

Contact information

Type

Public

Primary contact

Prof Luca Gabutti

ORCID ID

http://orcid.org/0000-0002-1929-6759

Contact details

Internal Medicine and Dialysis service
Regional Hospital of Bellinzona and Valli
Via Ospedale 1
Bellinzona
6500
Switzerland
+41 0918118464
luca.gabutti@eoc.ch

Type

Scientific

Additional contact

Dr Rosaria Del Giorno

ORCID ID

http://orcid.org/0000-0001-5206-8865

Contact details

Department of Internal Medicine
Regional Hospital of Bellinzona and Valli
Via Ospedale 1
Bellinzona
6500
Switzerland
-
rosaria.delgiorno@eoc.ch

Additional identifiers

EudraCT number

Nil known

ClinicalTrials.gov number

Nil known

Protocol/serial number

Nil known

Study information

Scientific title

Consequences of supraphysiological dialysate magnesium on arterial stiffness, hemodynamic profile and endothelial function in hemodialysis: observational cross-over study followed by a follow-up phase

Acronym

IDM

Study hypothesis

Dialysate magnesium at 0.75 mmol/L improves arterial stiffness, blood pressure, and endothelial function when compared to dialysate magnesium at 0.50 mmol/L in hemodialysis patients.

Ethics approval

Approved 29/05/2018, the Swiss Ethics Commission (Comitato etico cantonale
c/o Ufficio di sanità, Via Orico 5, 6501 Bellinzona, Switzerland; +41 (0) 91 814 30 57; dss-ce@ti.ch), ref: CE3358, BASEC2018-00830.

Study design

Single-centre randomized crossover study followed by an observational follow-up phase

Primary study design

Interventional

Secondary study design

Randomised cross over trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Not available in web format, please use contact details to request a participant information sheet

Condition

Arterial stiffness, hemodynamic profile and endothelial function in hemodialysis patients

Intervention

4-week cross-over study aimed at investigating the consequences of increasing dialysate magnesium (D-Mg2+) from 0.50 to 0.75 mmol/L on arterial stiffness, hemodynamic profile, and endothelial function in subjects undergoing hemodialysis (HD).

The long-term effect of higher D-Mg2+ (0.75 mmol/L) on mineral metabolism markers will be investigated in a six-month follow-up.

After enrolment, patients will be randomly assigned to a 2-week treatment (6 HD sessions) with either standard dialysate magnesium (Group 1, who will receive D-Mg 2+ 0.50 mmol/L treatment) or high dialysate magnesium (Group 2, who will receive D-Mg 2+ 0.75 mmol/L treatment). This will be followed by a 3-day washout period (in which HD treatments were not carried out), and then a second 2-week cross-over phase (further 6 HD sessions where the Group 1 participants will receive high dialysate magnesium and the Group 2 participants will receive standard dialysate magnesium). There will be 12 haemodialysis sessions over the course of the 12 weeks. Assessments will be made at the start, at the point of cross over, and at the end of the 4-week period.

After the 4 weeks of cross-over, subjects continuing dialysis will receive D-Mg2+ set at 0.75 mmol/L, as already planned for every patient by the internal guidelines of the network to whom the dialysis center of the study belongs.

Patients will be followed for a further 6 months to explore metabolic long term-changes related to high dialysate magnesium (0.75 mmol/L).

Intervention type

Drug

Phase

Not Specified

Drug names

Dialysate magnesium 0.50 mmol/L and 0.75 mmol/L

Primary outcome measure

1. Vascular stiffness as estimated by pulse wave velocity (PWV), augmentation index (AI), and pulse pressure (PP) using a conventional brachial cuff for adults with an integrated high-fidelity pressure sensor, Mobil-o-Graph on the non fistula arm to assess systolic blood pressure, diastolic blood pressure, and heart rate which are assessed 3 times (at the beginning, after half of the time and at the end) during each haemodialysis session between baseline and 4 weeks

Secondary outcome measures

1. Hemodynamic profile measured using a conventional brachial cuff for adults with an integrated high-fidelity pressure sensor, Mobil-o-Graph on the non fistula arm to assess systolic blood pressure, diastolic blood pressure, and heart rate which are assessed 3 times (at the beginning, after half of the time and at the end) during each haemodialysis session between baseline and 4 weeks.
2. Endothelial function, as measured by the reactive hyperemia index estimated with a validated, non operator-dependent, device for non-invasive measurement of endothelial function (EndoPAT 2000, Itamar Medical Inc., Israel) at baseline and 2 and 4 weeks
3. Incidence of intradialytic hypotension and bradicardia measured using a conventional brachial cuff for adults with an integrated high-fidelity pressure sensor, Mobil-o-Graph on the non fistula arm to assess systolic blood pressure, diastolic blood pressure, and heart rate which are assessed 3 times (at the beginning, after half of the time and at the end) during each haemodialysis session between baseline and 4 weeks. Intradialytic hypotension is defined as a decrease in systolic blood pressure of ≥20 mmHg or a decrease in mean arterial pressure (MAP) of ≥10 mmHg, and intradialytic bradycardia as an heart rate of ≤60 beats/min.
4. Incidence of pre-/post-dialytic hypermagnesaemia or hyper-/hypo-calcemia measured from ionized magnesium and ionized calcium using an ionometer (Microlyte 6 Analyzer, Kone Instruments, Espoo, Finland) pre- and post-haemodialysis at each haemodialysis session between baseline and 4 weeks
5. Changes in mineral and bone metabolism markers over the 6-month follow up period measured using ionized calcium and ionized magnesium assessed at 0, 1, 2, 3, 4, 5, and 6 months of follow up, and intact parathyroid hormone, 25-OH-Vitamin D, ionized magnesium and total magnesium levels assessed at 0, 3 and 6 months of follow up

Overall trial start date

05/05/2017

Overall trial end date

30/07/2019

Reason abandoned (if study stopped)

Eligibility

Participant inclusion criteria

1. Receiving treatment in the participating center with maintenance hemodialysis for ≥3 months
2. Aged ≥18 years
3. Able to understand the protocol and to give written informed consent

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

40

Total final enrolment

40

Participant exclusion criteria

1. Acute illness requiring hospitalization
2. Pregnancy or risk of pregnancy

Recruitment start date

20/08/2018

Recruitment end date

31/12/2018

Locations

Countries of recruitment

Switzerland

Trial participating centre

Dialysis center of the Regional Hospital of Bellinzona and Valli
Via Ospedale 1
Bellinzona
6500
Switzerland

Sponsor information

Organisation

Ente Ospedaliero Cantonale

Sponsor details

Internal Medicine and Dialysis Services
Regional Hospital of Bellinzona and Valli
Via Ospedale 1
Bellinzona
6500
Switzerland
+410918119464
clinicaltrialunit@eoc.ch

Sponsor type

Hospital/treatment centre

Website

http://www.eoc.ch/en/

Funders

Funder type

Hospital/treatment centre

Funder name

Scientific Research Advisory Board (ABREOC) of the Ente Ospedaliero Cantonale

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

Planned publication in a high-impact peer-reviewed journal

IPD sharing statement:
The datasets generated during and/or analysed during the current study are not expected to be made publicly available as participant consent forms and ethics approval did not include permission for secondary use, with access to data only approved for researchers involved in the analysis.

Intention to publish date

01/12/2020

Participant level data

Not expected to be available

Basic results (scientific)

Publication list

Publication citations

Additional files

Editorial Notes