Magnesium in chronic haemodialysis (MAGIC-HD): a study protocol for a randomised controlled trial to determine feasibility and safety of using increased dialysate magnesium concentrations to increase plasma magnesium concentrations in people treated with haemodialysis

Abstract

Introduction: People treated with haemodialysis are at increased risk for all-cause and cardiovascular mortality. Plasma magnesium concentration has been inversely associated with these risks. Therefore, plasma magnesium may be a new modifiable risk factor and an increase of dialysate magnesium concentration may be an easy, safe and effective way to increase plasma magnesium concentrations. Detailed information on modulating dialysate magnesium concentrations is limited in literature. Primary objective of this study is to determine the safety and feasibility to increase plasma magnesium concentrations in people treated with haemodialysis by means of sequentially increasing concentration of magnesium in the dialysate.

Methods and analysis: In this randomised double-blinded standard of care controlled trial, 53 persons treated with haemodialysis will be randomly allocated 2:1 to either a stepwise individually titrated increase of dialysate magnesium concentration from 0.50 to 0.75 to 1.00 mmol/L during 8 weeks, or a standard dialysate magnesium concentration of 0.50 mmol/L. Other study measurements include dietary records, questionnaires, ECG, Holter registration and pulse wave velocity. The primary endpoint is predialysis plasma magnesium after the long interdialytic interval at the end of week 8. In addition, the predictive effect of dialysate magnesium concentration and other baseline parameters and dialysis characteristics on plasma magnesium concentration will be explored using linear mixed models. Safety endpoint is defined by the occurrence of hypermagnesemia above 1.25 mmol/L, or bradycardia or prolonged QTc interval detected on the ECG.

Ethics and dissemination: The study is conducted in accordance with the declaration of Helsinki as revised in 2013 and was approved by the Ethical Committee of the VU University Medical Centre. The results of the study will be disseminated by publication in peer-reviewed scientific journals and presentation at national or international conferences in the field of interest.

Trial registration number: NTR6568/NL6393.

Keywords: dialysis; end stage renal failure; nephrology.

Figure 1

Flow chart of the study intervention. Numbers within frames represent dialysate magnesium concentrations in mmol/L. All other magnesium concentrations represent plasma magnesium concentrations, also in mmol/L. Mg, magnesium; Δ, ECG criteria at baseline: bradycardia defined as heartrate <60 bpm or prolonged QTc interval >450 ms in male or >460 ms in female; ΔΔ, ECG criteria in week 4: bradycardia with heart rate <50 bpm or prolonged QTc interval >450 ms in male or >460 ms in female; *predialysis plasma Mg concentration after the long interdialytic interval; **plasma Mg concentration at any time point (predialysis and postdialysis measurements included).

Figure 2

Study procedures. Dialysis 1, dialysis 2 and dialysis 3, first, second and third dialysis sessions after the long interdialytic interval of the week respectively; pre, predialysis; post, postdialysis; blood sampling set 1, lithium heparin gel tube for plasma magnesium measurement; set 2, lithium heparin gel tube for plasma magnesium and potassium measurement; set 3, lithium heparin gel tube for plasma magnesium, potassium, calcium, albumin, phosphate, bicarbonate, CRP and 2x EDTA tube for haemoglobin and PTH; set A, serum tube for biobanking in participants who provided additional informed consent; set B, 2x EDTA tube for biobanking in participants who provided additional informed consent; ECG, predialysis ECG; Questionnaire, 7-point yes or no questionnaire to ask if a participant experienced the following symptoms in the last week: nausea, vomiting, dizziness, drowsiness and reduced muscle strength, itching and leg cramps, in addition at baseline a question about chronic diarrhoea and over-the-counter use of magnesium supplements is included; 3DDD, 3 days dietary diary including one dialysis weekday, one non-dialysis weekday, one non-dialysis weekend day; Holter, 48-hours ECG registration including one dialysis session and one interdialytic interval; PWV, pulse wave velocity measurement before the mid-week dialysis session. CRP, C-reactive protein; PTH, parathyroid hormone.