Clinical trial NCT03840226: The Impact of Magnesium on Exercise Tolerance, Quality of Life and Clinical Outcomes in Chronic Heart Failure Patients
Official title: The Impact of Magnesium Oxide Monohydrate Compared to Placebo on Exercise Tolerance, Quality of Life and Clinical Outcomes in Chronic Heart Failure Patients
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Magnesium Deficiency
Heart Failure
Keywords: magnesium
heart failure
Lead sponsor: Sheba Medical Center
Sponsor class: OTHER_GOV
Collaborators: name: Naveh Pharma (1996) Ltd.
First posted: 2019-02-15
Enrollment: 320
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: The aim of the study is to test The impact of magnum versus placebo, on six-minute and clinical outcomes of patients with CHF (level 2-4).

The Primary endpoints are:

1. Improvement in Six-Minute walk test.
2. Improvement in clinical outcomes: death, CHF hospitalization, revascularization etc.

To test the hypothesis that the six-minute results between the two study groups are different, with significance level of 5% and power of at least 80%, we use the t-test. Based on Monica et al (2001), the mean six-minute results among these patients is 218 with SD=28. for an expected difference of at least 10 meter, we need a sample size of 125 patients in each group.
Primary purpose: TREATMENT

Brief summary: Magnesium supplementation could improve cardiac performance. Patients with chronic heart failure (CHF) are magnesium deficient and we hypothesized that 1 year supplementation of oral magnesium comparted to placebo will improve exercise duration time and quality of life.

Detailed description: Magnesium supplementation improves myocardial metabolism, inhibits calcium accumulation and myocardial cell death; it improves vascular tone, peripheral vascular resistance, afterload and cardiac output, reduces cardiac arrhythmias and improves lipid metabolism. Magnesium also reduces vulnerability to oxygen-derived free radicals, improves human endothelial function and inhibits platelet function. Patients with chronic heart failure (CHF) are magnesium deficient. The activation of the renin-angiotensin-aldosterone system and the use of diuretics are associated with depletion of potassium and magnesium in CHF. Magnesium deficiency stimulates aldosterone production and secretion, while magnesium infusion decreases aldosterone production production by inhibiting cellular calcium influx. Adamopoulos et al recently found that CHF in patients \[mainly New York Heart Association (NYHA) II-II\] with low serum magnesium ≤ 2 mEq/L was associated with increased cardiovascular mortality (but had no association with cardiovascular hospitalization) compared to those with serum magnesium \> 2 mEq/L in a long-term follow-up of 36 months, suggesting that most of these deaths were likely sudden (arrhythmic) in nature.

Furthermore, Stepura and Martynow demonstrated that oral magnesium orotate used as adjuvant therapy in severe NYHA IV CHF patients increased 1-year survival rate and improved clinical symptoms and patient's quality of life compared to placebo. The investigators hypothesized that 1-year supplementation of oral magnesium compared to placebo to CHF patients will improve exercise duration time and quality of life.

Eligibility criteria: Inclusion Criteria:

* CHF patients NYHA II-IV \> 3 months
* Diuretic therapy \> 3 months
* Signed informed consent

Exclusion Criteria:

* chronic renal failure (serum creatinine \> 3 mg/dL)
* AMI/ACS\< 3 months from randomization
* Cardiac or other organ transplantation
* Uncontrolled hypo/hyperthyroidism
* Chronic diarrhea
* Life expectancy \< 1 year
* Known psychiatric disease which inhibits patient's enrollment to the study
* Inability to come for follow-up visits
* Any planned operation/invasive procedures in the near 6 months
* Uncontrolled cardiac arrhythmias
* Inability to perform 6 minute walk testing
* Any participation in another interventional clinical trial \< 1 month from randomization
* Any malignancy with life expectancy \< 1 year Any AV Block\> 2 degree without a pacemaker

Primary outcomes:
measure: Improvement in exercise duration time
timeFrame: 1 year
measure: Qaulity of life
timeFrame: 1 year
Secondary outcomes:
measure: Improvment in the number of hospitalizations for heart failure
timeFrame: 1 year
Other outcomes:
Locations:
city: Ramat Gan
country: Israel
facility: Leviev Heart Center, Chaim Sheba Medical Center
Study officials:
affiliation: Sheba Medical Center
name: Michael Shechter, MD
role: PRINCIPAL_INVESTIGATOR
References: