Main Objective: - Determine feasibility to increase plasma magnesium concentrations in hemodialysis patients by means of increased concentration of magnesium in the dialysate. Secondary Objectives:- Determine safety of increasing plasma magnesium…
ID
Source
Brief title
Condition
- Cardiac disorders, signs and symptoms NEC
- Nephropathies
- Arteriosclerosis, stenosis, vascular insufficiency and necrosis
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
- The difference between plasma magnesium concentration in the intervention
group and plasma magnesium concentration in the control group after the long
interdialytic interval at the end of week 8.
- The difference in change of plasma magnesium concentration after the long
interdialytic interval from baseline to the end of week 8 between the
intervention and the control group.
Secondary outcome
- The cumulative incidence of magnesium concentration >= 1.25 mmol/L in the
intervention group and in the control group.
- The cumulative incidence of prolonged duration of QTc (defined as >450ms in
male and >460ms in female) in the intervention group and in the control group.
- The cumulative incidence of bradycardia (defined as heart rate below 60 beats
per minute) in the intervention group and in the control group.
- The effect of dialysate magnesium concentration on pre-dialysis and
post-dialysis plasma magnesium concentration at the dialysis after the long
interdialytic interval.
- Predictive factors for the effect of dialysate magnesium concentration on
pre-dialysis and post-dialysis plasma magnesium concentration at the dialysis
after the long interdialytic interval.
- The difference in carotid-femoral pulse wave velocity in the intervention
group and the control group in week 8, and the difference in change of pulse
wave velocity from baseline to week 8 between the intervention group and the
control group.
Background summary
In hemodialysis patients, the risk for mortality and especially cardiovascular
mortality is substantially higher compared to the healthy population. This risk
can only partially be explained by traditional cardiovascular risk factors and
known kidney specific risk factors. In observational hemodialysis cohort
studies, lower serum magnesium levels are associated with overall and
cardiovascular mortality. It is currently unknown whether increasing plasma
magnesium concentrations in hemodialysis patients can decrease cardiovascular
mortality. To enable future studies on this topic, we first need to optimize
methods to increase plasma magnesium concentrations. In hemodialysis patients,
the dialysate might be an attrative route. Literature on the effect of
increasing dialysate magnesium concentrations on pre- and postdialysis plasma
magnesium is insufficient. This study can provide important information to
enable future studies focussed on improving cardiovascular outcome in
hemodialysis patients.
Study objective
Main Objective:
- Determine feasibility to increase plasma magnesium concentrations in
hemodialysis patients by means of increased concentration of magnesium in the
dialysate.
Secondary Objectives:
- Determine safety of increasing plasma magnesium concentrations by means of
increasing the concentration of magnesium in the dialysate.
- Determine the effect of dialysate magnesium concentrations on plasma
magnesium concentrations.
- Determine which parameters are predictive for the effect of dialysate
magnesium concentrations on plasma magnesium concentrations.
Study design
Randomized double-blind standard of care-controlled intervention trial.
Intervention
Stepwise increase of magnesium concentration in the dialysate:
- Week 0: continuation of standard 0.50 mmol/L dialysate magnesium
- Week 1, 2, 3, 4: dialysate magnesium 0.75 mmol/L
- Week 5, 6, 7, 8: dialysate magnesium 1.00 mmol/L if pre-dialysis plasma Mg
<1.15 mmol/L in week 4; dialysate magnesium 0.75 mmol/L if pre-dialysis plasma
Mg >=1.15 in week 4
- Week 9: dialysate magnesium concentration reduction of 0.25 mmol/L (to either
0.75 mmol/L or 0.50 mmol/L)
- Week 10, 11: dialysate magnesium 0.50 mmol/L
Study burden and risks
Burden and risks associated with participation:
- Blood sampling: before and after dialysis weekly from week 0 to 11 and every
dialysis session in week 1 and 5. Samples are taken from the dialysis circuit
so no additional puncture is needed.
- Questionnaires: 3 times 10 minutes
- 3-days dietary record: once
- ECG 3 times at the dialysis department
- Pulse wave velocity measurements 2 times at the dialysis department
- Holter-registrations: 2 times, installation of electrodes, 48h with the
device, no showering/swimming/sauna
- There is a very small risk for symptomatic hypermagnesemia. Symptoms of
severe hypermagnesemia typically do not develop at concentrations below 2.0
mmol/L and include nausea, vomiting, prolonged cardiac conduction times (QTc),
bradycardia, hypotension, muscle weakness and decrease of conscience. The
dialysate magnesium levels used in this study are not expected to cause
magnesium levels in this range and this risk is further minimized by intensive
monitoring of plasma magnesium levels and electrocardiography.
Benefits:
- There are no benefits for individual patients participating in this study.
However, this study can provide important information to enable future studies
focusing on improving cardiovascular outcome in hemodialysis patients.
De Boelelaan 1117
Amsterdam 1081 HV
NL
De Boelelaan 1117
Amsterdam 1081 HV
NL
Listed location countries
Age
Inclusion criteria
- Age 18 or above
- Hemodialysis with regular three times weekly dialysis schedule
- Hemodialysis since at least 3 months
- Standard dialysate Mg2+ concentration 0.50 mmol/L
- Providing informed consent
- Pre-dialysis plasma magnesium concentration 1.00 mmol/L or below
Exclusion criteria
- Intravenous magnesium supplementation (including total parenteral nutrition)
in the last 2 weeks
- Expected cessation of hemodialysis treatment within three months after
inclusion or expected permanent or temporary dialysis center switch to a center
not participating in the trial within three months after inclusion.
- Prolongation of QTc interval: male >450ms or female >460ms on baseline ECG
- Bradycardia: heart rate below 60 beats per minute on baseline ECG
- Chronic arrythmia or cardiac conduction disorder other than atrial
fibrillation or ventricular extrasystole that poses the patient at risk at the
discretion of the treating physician.
- Change of protonpumpinhibitor prescription in the last 2 weeks
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
In other registers
| Register | ID |
|---|---|
| CCMO | NL62679.029.17 |
| Other | registratie in behandeling, nummer volgt |
| OMON | NL-OMON23476 |