Magnesium Supplementation for the Prevention of Supraventricular Arrhythmias: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Magnesium Supplementation for the Prevention of Supraventricular Arrhythmias (NCT02837328), a randomized phase 2 study. The primary outcome is Change in Premature Atrial Contractions (PACs).

2. Clinical Question

3. Trial Design

This was a phase 2, randomized, triple-masked, parallel-group trial sponsored by the University of Minnesota. The registry lists the study as completed. It records a start date of 2017-03-01 and a primary completion date of 2017-09-15. Enrollment was 59.

Participants were assigned to oral magnesium supplementation or placebo. The magnesium arm received 400 mg magnesium citrate once daily for 12 weeks; the placebo arm received a pill described as resembling that supplement, on the same daily schedule and for the same duration. The registry classifies the interventions as drugs. It does not identify which groups of people were masked, so the exact meaning of triple masking in practice is not reported in the registry record.

The primary endpoint was change in PACs from baseline at 10 weeks, measured in episodes per hour. A secondary outcome was change in magnesium concentration, measured in mEq/L, with a timeframe listed as baseline and week 10. The registry lists two outcome measures. The reported arm sizes for the primary and secondary outcomes are 29 for magnesium and 30 for placebo.

The registry record does not report the original sample-size justification, the planned statistical model, the randomization procedure, or whether there were interim analyses. It also does not report participant flow, treatment adherence, losses to follow-up, or the analysis population. These omissions limit what can be said about how the trial was planned and how complete the endpoint data were. The posted summaries permit an unadjusted comparison of the group means, but do not supply the details needed to reconstruct a more extensive analysis plan.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Before assignment: Participants attended a baseline visit where measurements were conducted and a Zio XT Patch heart rhythm monitor was applied by trained staff. After wearing the patch for 2 weeks, the participants were randomized 1:1 to either magnesium oxide or a placebo using block randomization within two strata of age (younger than 65 and 65 and older).

Overall Study

5. Baseline Characteristics

The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.

6. Primary Endpoint

The registry lists the primary outcome as Change in Premature Atrial Contractions (PACs), measured over Change from Baseline at 10 weeks.

The primary endpoint measures change in premature atrial contraction burden from baseline at 10 weeks. PACs are extra beats that arise in the upper chambers of the heart. The registry expresses their burden as episodes per hour, so the measure represents the frequency of these events over time rather than a simple yes-or-no outcome. The posted endpoint is summarized as a mean and standard deviation for each arm.

Using PAC burden aligns directly with the stated research objective: examining whether oral magnesium supplementation is associated with changes in supraventricular arrhythmia burden. A change measure compares each participant's later burden with their baseline burden, then the group summaries describe the average change. Negative means indicate a reduction in the measure as coded in the registry results; they do not by themselves indicate which group changed more. The between-group mean difference is needed to describe that contrast.

The primary outcome is distinct from the secondary magnesium-concentration measure. PAC burden is the clinical rhythm measure identified as the main endpoint, while magnesium concentration is a biochemical measure. The registry does not report further detail on how PAC episodes were detected, how long monitoring lasted, or how missing or unusable measurements were handled. Without those details, the precision of measurement and the extent of endpoint completeness cannot be assessed from the registry record alone.

7. Results Posted in the Registry

• Oral Magnesium Supplement: mean -0.60 versus -5.60 on control; difference 5.00 (95% CI -7.08 to 17.08), standardized effect d = 0.21; z-test p = 0.417.

8. Secondary Efficacy Endpoints

The registry also posts results for secondary outcomes. For each outcome below, the endpoint type, the test applied to the posted summary statistics, the result and its interpretation are given in turn. Secondary endpoints are usually not adjusted for multiple testing, so they support rather than confirm the primary finding.

Change in Magnesium Concentration

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard deviations.
• Result:
  • Oral Magnesium Supplement: mean 0.07 versus 0.00 on control; difference 0.07 (95% CI 0.02 to 0.12), standardized effect d = 0.74; z-test p = 0.005.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the mean is statistically higher for Oral Magnesium Supplement than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

The secondary outcome concerns magnesium concentration, whereas the primary outcome concerns PAC burden. Together, they address different parts of the trial's research question: one is a biochemical measure and the other is the rhythm-burden endpoint. Their results should not be treated as interchangeable evidence. A change in a secondary biological measure does not, by itself, establish a corresponding change in the primary clinical measure.

The posted secondary comparison has a different statistical pattern from the primary comparison. That contrast may be useful for understanding the observed measurements, but the secondary endpoint is not a substitute for the prespecified primary question. The registry record identifies one secondary outcome and two outcome measures overall. It does not report a hierarchy for testing outcomes, a multiplicity adjustment, or an explanation of how secondary findings were intended to inform interpretation.

Unadjusted secondary results generally carry less weight when several outcomes are examined because each additional test creates more opportunity for a seemingly notable result to arise by chance. General statistical context: a multiplicity plan can control or otherwise address this issue by specifying priorities or adjusting inference across outcomes. No such plan is reported in the registry record, so the secondary result should be regarded as exploratory context rather than independent confirmation.

The broad pattern is therefore one of distinct endpoint information rather than a single unified treatment conclusion. The primary endpoint remains the main measure for the stated research objective. The secondary measure may help describe what happened to magnesium concentration in the two groups, but it does not resolve the uncertainty around the primary PAC comparison. Any interpretation should also account for the unreported analysis plan, missing-data handling, and analysis population.

Secondary outcomes registered for this trial, for reference (only those above were recalculated):

• Change in Magnesium Concentration

9. Statistical Interpretation

10. Statistical Methods Explained

Statistical methods help distinguish the observed group summaries from the uncertainty around their comparison. The registry reports continuous outcomes as means and standard deviations. A mean describes the average observed change in an arm; a standard deviation describes how spread out individual observations are around that average. The posted comparison is an unadjusted difference between the arm means. No covariate-adjusted or other model-based primary estimate is reported in the registry record.

What does the mean difference represent?

The primary mean difference is 5.0 episodes/hour, calculated as the magnesium-group mean change minus the placebo-group mean change. In this coding, a positive value means the magnesium group's mean change is higher than the placebo group's mean change. It does not mean that every participant's result followed that direction, and it does not describe the distribution of individual responses. A group-average contrast can conceal substantial variation among participants.

The recalculated comparison uses the posted arm means and standard deviations and is unadjusted. It is a simple comparison rather than a reproduction of a protocol-specified analysis. The registry record does not report the planned statistical test, any covariates, a model for repeated observations, or the handling of departures from model assumptions. The recalculated estimate should therefore be interpreted as a descriptive inferential summary based on the posted statistics.

What do standard deviations tell us?

A standard deviation describes participant-to-participant spread, not the precision of the arm mean itself. The primary endpoint's posted standard deviations are 7.0 in the magnesium arm and 33.0 in the placebo arm. The values indicate that the observed changes were more dispersed in the placebo group according to these summaries. They do not reveal whether the data were symmetric, skewed, or influenced by extreme observations. Those features would require more detailed data or plots, which are not reported in the registry record.

General statistical context: PAC episodes are event-like observations, and event measures can sometimes have many low values and a smaller number of high values. When a count outcome varies more than a statistical model expects, that is called over-dispersion. A model that ignores over-dispersion can understate uncertainty. The posted analysis summarizes episodes per hour as a continuous mean with a standard deviation; the registry record does not report a count model or an over-dispersion assessment. This possibility is a general consideration, not a claim about the distribution in this trial.

How should the p-value be read?

The unadjusted p-value for the primary comparison is 0.417. In general, a p-value measures how unusual the observed data, or data more extreme, would be under a specified null hypothesis and statistical model. It is not the probability that the null hypothesis is true, and it does not measure the magnitude or clinical importance of a difference. Here the exact test and its assumptions are not reported in the registry record, so the posted p-value should be read as an unadjusted result whose calculation method is unspecified.

Interpretation should consider the estimate and its confidence interval as well as the p-value. A p-value alone cannot show which values remain compatible with the data, while the interval communicates the range of estimates compatible with the chosen procedure. The primary interval runs from -7.08 to 17.08 and includes zero. This is consistent with the unadjusted p-value not giving strong evidence against a zero difference under the associated testing framework, but neither quantity proves that the groups are equivalent.

Why does the analysis plan matter?

A trial's plan can specify how outcomes are defined, which population is analyzed, what statistical model is used, and how multiple outcomes are handled. These choices affect the interpretation of estimates and uncertainty. The registry record does not report the original statistical analysis plan, the planned primary test, the analysis population, missing-data methods, or a multiplicity adjustment. Accordingly, the posted summary does not establish whether the unadjusted recalculation matches the analysis that investigators intended before seeing results.

General statistical context: randomization is intended to make assigned groups comparable on average, but it does not guarantee balance on every characteristic in a particular trial. Baseline measurements and allocation details can help readers evaluate the comparison. They are not reported in the registry record in enough detail to assess balance. The randomized design remains important context, but the summaries alone cannot resolve all design and analysis questions.

The secondary concentration outcome is also a mean-based continuous measure. It is reported with arm summaries and an unadjusted mean contrast. Because the registry identifies it as secondary, its result should be interpreted alongside the primary endpoint and any multiplicity plan. No such plan is reported. The reported results therefore support a cautious, outcome-specific reading rather than a broad conclusion based on one favorable-looking statistical result.

11. Confidence Intervals and Precision

The primary estimate is a mean difference of 5.0 episodes/hour, with a 95% confidence interval from -7.08 to 17.08. The interval is wide enough to include zero and values on either side of zero. Thus the posted summary does not pin down the direction or size of the underlying between-group difference with high precision. The estimate of 5.0 is the center of the interval, not a guarantee that the true difference is exactly that value.

General statistical context: a confidence interval is produced by a procedure that, under its assumptions and repeated use, would cover the true parameter at the stated rate. For an individual trial, it is commonly read as a range of values reasonably compatible with the data and procedure. It is not a range containing a stated proportion of individual participants' responses. Here, the interval's interpretation depends on the calculation assumptions, and the registry record does not report the test or model used for an official primary analysis.

The arm summaries show 29 participants in the magnesium group and 30 in the placebo group. The standard deviations differ, with 7.0 in the magnesium group and 33.0 in the placebo group. The combination of the observed variability and the limited number of participants contributes to uncertainty in a group comparison. The summaries do not allow the contribution of each factor to be separated, nor do they show how the estimate would change under alternative assumptions.

Precision is not the same as statistical significance or clinical importance. A narrow interval can be precise without establishing that a difference matters to patients, while a wide interval can leave several interpretations open. The primary interval indicates that this comparison is not a precise estimate of the magnitude of the difference. The registry record does not state a threshold for a clinically important PAC change, so the clinical meaning of particular values within the interval cannot be determined from the posted results alone.

12. Planning a Similar Trial: Sample Size

This is a planning illustration, not a re-evaluation of the original trial. It asks: if a new study wanted to detect a difference like the one observed, or a smaller one, how large would it need to be? It is deliberately not “observed power” of the finished trial, which is not a meaningful quantity.

The planning figures are expressed as participants per arm, not total events. They are illustrations calculated from the observed effect, not the trial's own original design assumptions; those original assumptions are not reported in the registry record. The stated planning assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. The effect to detect is set to a stated fraction of the observed effect.

The 80% power column gives the estimated participants per arm for a hypothetical study designed to have an 80% chance of detecting the specified effect under those assumptions, if that effect and the planning model were correct. The 90% power column uses a higher target chance of detection, so its participant requirements are larger. These figures describe hypothetical planning, not the probability that the completed trial's result is correct.

For the primary endpoint, the planning rows consider 100% of the observed effect, 75% of the observed effect, and 50% of the observed effect. The associated estimates are 364 and 486 participants per arm for 100% of the observed effect; 646 and 864 for 75%; and 1,453 and 1,944 for 50%, at the 80% and 90% targets respectively. Smaller effects need more participants to detect under the same assumptions, because they are harder to distinguish from random variation.

This is not observed power. It is a planning illustration based on the effect observed in this trial, and observed effects can be unstable, especially when the estimate is imprecise. The calculations do not establish what sample size was intended for the trial or whether its original design was adequate. The registry record does not report that original design justification.

13. How the Sample Size Is Derived

Power is the probability that a study of a given size rejects the null hypothesis when a specific true effect exists. It depends on four things: the effect to detect, the variability of the outcome, the significance level (here a two-sided α of 0.05, so z_1−α/2 = 1.960) and the desired power (z_1−β = 0.842 for 80% and 1.282 for 90%).

Formula

n is the number of participants in each arm, Δ is the difference in means to detect and σ is the common standard deviation.

Worked calculation for this trial

1. Observed difference Δ = 5.000; pooled standard deviation σ = 24.044.
2. n = 2 × (1.96 + 0.842)² × 24.044² / 5.000² = 363.0, rounded up to 364 participants per arm for 80% power.

The smaller-effect rows in the table above repeat the same calculation with the effect multiplied by 0.75 and 0.5 (for ratios, applied to the logarithm of the ratio).

R code

alpha <- 0.05
z_a   <- qnorm(1 - alpha / 2)          # two-sided
delta <- 5                      # observed difference in means
sigma <- 24.0441844739543                     # pooled standard deviation
n_per_arm <- function(power, frac = 1) {
  ceiling(round(2 * (z_a + qnorm(power))^2 * sigma^2 / (delta * frac)^2, 6))
}
for (f in c(1, 0.75, 0.5))
  cat(sprintf("%3.0f%% of observed effect: n per arm = %s (80%% power), %s (90%% power)\n", 100 * f,
              format(n_per_arm(0.80, f), big.mark = ","), format(n_per_arm(0.90, f), big.mark = ",")))

# Check against R's built-in function (t-based, so very slightly larger)
cat("power.t.test:", round(power.t.test(delta = delta, sd = sigma, power = 0.80)$n, 1), "\n")

# Simulation: exact two-sample t-test using simulated means and variances
set.seed(2837328)
n    <- n_per_arm(0.80)
reps <- 20000
m_diff <- rnorm(reps, delta, sigma * sqrt(2 / n))             # difference in sample means
s2     <- sigma^2 * rchisq(reps, 2 * (n - 1)) / (2 * (n - 1))   # pooled sample variance
tstat  <- m_diff / sqrt(s2 * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(tstat) > qt(0.975, 2 * (n - 1))), reps))

Output from running the code

100% of observed effect: n per arm = 364 (80% power), 486 (90% power)
 75% of observed effect: n per arm = 646 (80% power), 864 (90% power)
 50% of observed effect: n per arm = 1,453 (80% power), 1,944 (90% power)
power.t.test: 364 
Simulated power at n = 364 per arm: 0.799 (20000 replicates)

The simulation draws many sets of group means and variances at the planned sample size and counts how often the two-sample t-test rejects the null. It should land close to the target power; at very small required sample sizes it can fall below it, because the normal approximation is rough there.

14. Multiplicity, Missing Data and Analysis Populations

The registry lists a primary PAC endpoint and a secondary magnesium-concentration outcome, for two outcome measures overall. It does not report a multiplicity strategy, such as an adjustment across outcomes or a prespecified hierarchy that would determine how to interpret multiple tests. The posted secondary comparison is unadjusted. Without a stated plan, the chance of obtaining a small p-value across multiple outcomes cannot be assessed from the record.

The registry record also does not report how missing endpoint measurements were handled. It does not state whether all randomized participants were included in the analysis, whether any participants were excluded after assignment, or whether analyses followed an intention-to-treat approach. The reported arm counts are 29 and 30, but those counts alone do not establish how many participants had complete measurements at the endpoint or how missing values were treated.

Further details that would help evaluate the analysis are not reported in the registry record, including the planned statistical model, covariate adjustment, handling of unusual observations, and whether the analysis population was defined before results were examined. There are no reported formal analyses in the registry record. The posted arm summaries and the unadjusted comparisons allow a basic statistical reading, but they do not answer these design and analysis questions.

General statistical context: missing-data methods can affect estimates when the probability of missingness is related to participant characteristics or outcomes. Likewise, multiple testing can make an isolated small p-value less persuasive if many outcomes or analyses were considered. These are general concerns; the record does not establish that either problem occurred in this trial. The absence of reporting means that readers cannot determine how these issues were addressed, rather than proving that they were handled incorrectly.

15. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 0% reporting threshold.

Most frequent non-serious adverse event terms

The posted serious adverse-event figures list zero affected participants among 29 at risk in the oral magnesium group and zero among 30 at risk in the placebo group. The death counts are also zero in both groups. These figures describe what is recorded for the trial; they do not show that the risk of serious events is absent, particularly because the groups are small and the observation period is limited to the trial record.

The registry also reports other adverse events affecting 15 participants in the magnesium group and 2 in the placebo group. These are counts of participants affected, not necessarily counts of individual event episodes. The record does not report the specific terms for these other events in the information, their severity, or whether investigators considered them related to treatment. No serious adverse-event terms are listed.

Safety counts require context about how events were collected, the time at risk, and which participants contributed data. Further details about those procedures are not reported in the registry record. The counts are descriptive and should not be used alone to establish comparative safety.

16. What the Result Does, and Does Not, Mean

The registry results describe a randomized comparison of oral magnesium supplementation and placebo in 59 enrolled participants. The primary outcome was change in PAC burden at 10 weeks. The posted unadjusted mean difference is 5.0 episodes/hour, with a 95% confidence interval from -7.08 to 17.08 and an unadjusted p-value of 0.417. The interval includes no difference and a range of contrasts in both directions, so the primary estimate is uncertain.

That uncertainty is not the same as proof that the groups are equivalent. Equivalence requires a defined margin and an analysis designed to assess whether plausible differences stay within that margin. Neither an equivalence margin nor such an analysis is reported in the registry record. Likewise, the result does not establish that magnesium changes PAC burden in one direction or another. It describes the observed group summaries and their unadjusted comparison.

The trial's size, the spread in the posted primary outcome, and the breadth of the interval matter when considering how precisely the result applies beyond the participants enrolled. The record does not provide baseline characteristics, participant-level outcomes, or enough information about measurement and missing data to evaluate representativeness or the robustness of the estimate. The enrolled group is described generally as healthy, community-living individuals, but more specific population details are not reported.

The secondary magnesium-concentration measure provides a separate kind of information; it cannot establish the primary PAC result. Nor can the adverse-event counts alone settle broader questions about safety. The registry record does not report a full statistical analysis plan, multiplicity handling, or formal adjusted analyses. The most defensible reading is therefore limited: the posted summaries show an imprecise primary comparison and a distinct secondary measure, with important analytical details not reported in the registry record.

These results are not medical advice and should not be used to decide whether an individual should take magnesium. They are a description of one completed trial's posted outcomes, not a definitive statement about treatment effects in other people or settings.

17. Why This Trial Matters Statistically

This trial illustrates why an estimate should be read alongside its uncertainty. The primary comparison is reported as a difference between means, but its confidence interval spans zero and extends in both directions. A single point estimate cannot communicate that uncertainty. The interval makes clear that the data do not precisely establish the direction or magnitude of the group contrast.

The summaries also illustrate the importance of variability. The standard deviations for the primary endpoint differ notably between arms, while the total enrollment was 59. Mean-based summaries remain informative, but variability and distribution shape influence how stable a mean comparison may be. With only arm-level summaries, readers cannot inspect individual observations, evaluate outliers, or test alternative distributional assumptions.

The registry record also shows why outcome roles matter. A secondary biochemical measure can add context, but it is not equivalent to the primary rhythm-burden endpoint. If several outcomes are examined, a prespecified multiplicity approach helps distinguish planned confirmatory testing from exploratory findings. The record does not report such an approach, limiting the weight that can be placed on an isolated secondary result.

Finally, a randomized label does not supply every detail needed to assess the analysis. Sample-size justification, allocation procedures, missing-data handling, analysis populations, and a formal statistical plan are not reported in the registry record. These details influence how confidently a reader can interpret posted estimates. The trial is statistically informative as an example of a small randomized comparison with continuous outcomes, but its public summary leaves material questions about precision and analysis unanswered.

18. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

The principal limitation of the posted evidence is the imprecision of the primary comparison. The confidence interval ranges from -7.08 to 17.08 episodes/hour, which leaves uncertainty about both direction and magnitude. The primary arm summaries also show different standard deviations. Without participant-level data or a reported model, it is not possible to evaluate whether the mean comparison is sensitive to distributional features or unusual observations.

The enrolled sample was 59, with 29 participants in the magnesium arm and 30 in the placebo arm. The registry does not report the trial's original sample-size justification, so it is not possible to determine the intended target effect or planned power from the record. Planning illustrations based on the observed effect are not a substitute for that original justification.

Important trial details are not reported in the registry record, including baseline characteristics, participant flow, endpoint completion, adherence, allocation procedures, who was masked, and the method used to measure PACs. The record also does not report an analysis population, missing-data method, formal primary statistical model, or multiplicity plan. These omissions limit assessment of bias, generalizability, and robustness.

Finally, the posted summaries do not provide a threshold for a clinically important change in PAC burden. This prevents interpretation of the interval in terms of a stated clinical benchmark. The secondary result and adverse-event counts add context, but neither resolves the uncertainty in the primary endpoint. These are limitations of what can be assessed from the registry record; they do not establish that the underlying trial procedures were inadequate.

19. Related Tutorials

20. Related Statistical Calculators

21. Sources

• ClinicalTrials.gov: Magnesium Supplementation for the Prevention of Supraventricular Arrhythmias — NCT02837328.
• Registry record last updated 2019-11-01; status last verified 2019-10.
• Results first posted 2019-04-30.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

22. Record Summary

NCT02837328 is a completed phase 2 randomized, triple-masked, parallel-group trial sponsored by the University of Minnesota. It enrolled 59 participants and compared oral magnesium supplementation with placebo. The supplement was 400 mg magnesium citrate once daily for 12 weeks; the placebo pill was described as resembling the supplement.

The primary endpoint was change in PAC burden from baseline at 10 weeks, measured in episodes per hour. The unadjusted mean difference was 5.0, with a 95% confidence interval from -7.08 to 17.08 and an unadjusted p-value of 0.417. One secondary outcome measured change in magnesium concentration. Serious adverse events and deaths were recorded as zero in both groups; other adverse events affected 15 participants in the magnesium group and 2 in the placebo group.

The registry record does not report the original sample-size justification, a full analysis plan, multiplicity handling, or missing-data methods. The posted primary comparison is therefore best read as an imprecise, unadjusted summary of the trial results.