RECOVER-AUTONOMIC Platform Protocol: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for RECOVER-AUTONOMIC Platform Protocol (NCT06305780), a randomized phase 2 study. The primary outcome is Total Number of Participants Enrolled in Each Appendix.

2. Clinical Question

3. Trial Design

RECOVER-AUTONOMIC is a prospective, multicenter, randomized, controlled platform protocol. The registry identifies it as phase 2, with a parallel-group model and triple masking. It is designed to evaluate more than one intervention for autonomic dysfunction symptoms in PASC, rather than to report a single conventional two-arm clinical comparison. The interventions listed include IVIG and ivabradine, with placebo and coordinated-care or usual-care combinations.

The IVIG appendix is described as using 1:1:1:1 allocation among combinations of IVIG or placebo and coordinated or usual non-pharmacologic care. Its treatment period is described as 9 months (36 weeks), followed by an additional 3 months. The ivabradine appendix is also described as using 1:1:1:1 allocation across medication or placebo and coordinated or usual care. Its treatment period is 3 months (12 weeks), followed by an additional 3 months. The detailed protocol, including how platform-level allocation and any comparisons were operationalized, is not reported in the registry record.

The registry reports enrollment of 381 and lists the status as completed. The dates recorded are a study start of 2024-03-11 and primary completion of 2025-07-09. These design and status details describe the study framework, but they do not establish the effectiveness or safety of any intervention. The one posted primary outcome is enrollment by appendix. No clinical efficacy outcome analysis is posted in the registry record.

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 were excluded prior to assignment due to failure to meet eligibility criteria, safety or medical considerations identified during screening, inability to complete required assessments, or withdrawal of consent before randomization.

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 Total Number of Participants Enrolled in Each Appendix, measured over During the enrollment period, approximately 16 months.

The primary endpoint is the total number of participants enrolled in each appendix during the enrollment period, described as approximately 16 months. The posted counts are 200 for the IVIG appendix and 181 for the ivabradine appendix. This is an enrollment or study-conduct measure: it describes how many participants entered each appendix, rather than what happened to participants’ symptoms or health after treatment.

Enrollment counts can be useful for understanding recruitment and the scale of activity in different parts of a platform protocol. They do not estimate a treatment effect. In particular, a count cannot establish whether IVIG, ivabradine, placebo, coordinated care, or usual care changed autonomic dysfunction symptoms. Nor does enrollment by itself tell whether groups were comparable at baseline, whether participants completed treatment, or whether outcomes were measured consistently.

The endpoint description does not specify a symptom scale, clinical threshold, assessment schedule, or definition of a response. Those details are not reported in the registry record. The posted primary result should therefore be interpreted narrowly as appendix-level enrollment counts, not as evidence about clinical benefit, harm, or the course of PASC.

7. Results Posted in the Registry

• Ivabradine: 100.0% (181/181) versus 100.0% (200/200) on control; risk difference 0.0 percentage points (95% CI 0.0 to 0.0), risk ratio 1.00 (1.00–1.00); unadjusted two-proportion z-test p = n/a.

8. Statistical Interpretation

9. Statistical Methods Explained

What does randomization mean in this record?

Randomization assigns participants to study groups using a chance-based process. In general, this can reduce systematic differences between groups at the time of assignment, supporting a fair comparison when outcomes and analyses are appropriately defined. The registry identifies this study as randomized, but its posted primary measure is enrollment by appendix. Randomization does not turn a recruitment count into an outcome comparison, and the registry record does not report an analysis of clinical outcomes by randomized treatment group.

The appendices are each described as having 1:1:1:1 allocation among combinations of medication or placebo and coordinated or usual care. The record lists the corresponding intervention combinations. Details of sequence generation, concealment, implementation, and any adaptation of the platform are not reported in the registry record.

What does masking mean?

The registry records triple masking. In general, masking is intended to limit the influence of knowledge about treatment assignment on participant experience, care, outcome assessment, or analysis. The identity of the masked groups or roles is not reported in the registry record, so the specific implementation cannot be described further. A masking label alone does not establish that masking was maintained or that it affected any particular outcome.

What does the posted comparison represent?

The primary measure is a count of participants enrolled in each appendix. For a clinical binary outcome, an analysis might compare the proportion of participants experiencing an event in each treatment group. The registry comparison fields are labeled as a risk difference and show proportions of 1.0 for both appendices, alongside counts equal to their listed denominators. In this context, those fields appear tied to the enrollment-count outcome rather than a clinical event outcome. The record does not explain the calculation. They should not be read as evidence that clinical risk was identical across treatments.

A risk difference is generally the difference between two event proportions. Its meaning depends on the outcome, the populations being compared, and the analysis definition. Here, the posted endpoint is enrollment count, and no clinical event outcome is identified for the comparison. The confidence interval reported with that comparison therefore does not convey precision for a treatment effect on symptoms or safety.

Why are confidence intervals useful?

In general, a confidence interval expresses the uncertainty associated with an estimate under a statistical model and analysis procedure. A narrow interval can indicate that an estimate is statistically precise for the quantity being estimated; it cannot make an inappropriate or unclear quantity clinically meaningful. The registry reports an interval from 0.0 to 0.0 for the stated risk difference. Because the comparison is associated with the enrollment counts, that interval should not be interpreted as precise evidence of no difference in clinical outcomes.

The record does not report the statistical model, interval method, assumptions, or a p-value for a clinical outcome analysis. It also does not report adjustment for covariates, handling of repeated measures, or subgroup analyses. Those methods cannot be inferred from the general description of a randomized platform trial.

What can planning calculations tell readers?

In general, sample-size planning uses assumptions about the outcome, target effect, variability, allocation, and statistical error rates to illustrate the size of a future study needed for a specified design. The planning assumptions recorded for this study describe illustrations based on an observed effect, a two-sided significance level of 0.05, equal allocation, and a normal approximation. Such calculations are planning illustrations, not observed power and not evidence about treatment efficacy.

The registry record does not report a trial-specific sample-size justification or an analysis that links a planned target to the posted enrollment counts. It is therefore not possible to determine from the record whether recruitment met a prespecified target, whether the trial was adequately powered for a clinical outcome, or whether any planning assumptions were satisfied. A sample-size illustration cannot fill the gap left by unreported clinical results.

Likewise, the fact that the overall status is completed does not describe the completeness of outcome data or the conduct of analyses. The registry lists zero analyses and no secondary posted outcomes. No protocol-level statistical analysis plan is reported in the registry record. Readers should separate the trial’s design labels from the analyses actually posted.

10. Confidence Intervals and Precision

The only displayed interval associated with a comparison is 0.0 to 0.0 for the stated risk difference. The corresponding proportions are both 1.0, derived in the posted record from the enrollment counts and their denominators. This interval has no apparent width at the displayed precision, but the meaning of that precision depends on what was estimated. The registry does not explain the comparison’s derivation, and its primary endpoint is enrollment count rather than a clinical event. It therefore does not quantify uncertainty about a clinical treatment effect.

For a clinically interpretable interval, the endpoint and comparison would need to describe a defined clinical outcome, such as a prespecified symptom measure or event, evaluated in relevant treatment groups. The registry record does not post such an estimate or its interval. It also does not report details such as outcome-specific denominators, missingness, or the analysis method that would allow readers to assess the precision of a clinical result.

Confidence intervals are useful in general because they show a range of values compatible with the data and method, rather than giving only a single estimate. Their interpretation is conditional on the validity of the underlying analysis. An interval for enrollment proportions cannot be repurposed as an interval for symptom improvement, and an interval’s apparent narrowness does not establish clinical certainty. The posted results permit description of recruitment counts, but not an assessment of the precision of comparative efficacy or safety estimates.

11. Multiplicity, Missing Data and Analysis Populations

The protocol is a platform trial with multiple interventions and care combinations. In general, testing several treatments, outcomes, or comparisons can increase the chance of finding an apparently notable result by chance unless the analysis plan accounts for the multiple tests. The registry record does not report a multiplicity strategy, a hierarchy of comparisons, or which comparisons were designated primary for clinical efficacy. No clinical outcome analyses are posted, so multiplicity adjustment cannot be assessed from the results.

The registry lists one primary outcome measure, enrollment by appendix, and no secondary outcomes or analyses. It does not report a statistical analysis plan that would clarify intended estimands, analysis populations, covariate adjustment, or decision rules. These omissions do not establish that such plans were absent from study materials; they mean that the relevant information is not reported in the registry record.

Missing data are also not characterized for clinical outcomes. The record does not report outcome-specific follow-up, withdrawals, exclusions, adherence, or how missing observations were handled. The intervention descriptions mention follow-up after treatment, but they do not provide completion rates or outcome-data completeness. Without these details, readers cannot judge whether missingness could affect an efficacy estimate.

The analysis population is not defined in the posted results. It is not stated whether any clinical analysis followed assigned treatment, included participants who received treatment, or used another population definition. The comparison entries for enrollment counts do not answer these questions. They should not be treated as a substitute for an intention-to-treat or other clinical analysis.

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

The result means that the registry records 200 participants enrolled in the IVIG appendix and 181 in the ivabradine appendix. These counts provide information about recruitment activity within the platform. The overall enrollment is listed as 381. The record identifies the study as completed, but that status does not change what the primary endpoint measures.

The result does not show whether IVIG or ivabradine improved autonomic dysfunction symptoms, cardiovascular complications, or POTS. It does not compare medication with placebo for a clinical outcome, nor does it establish whether coordinated care differed from usual care. The posted risk-difference comparison is tied to proportions of enrolled participants and is not a clinical efficacy estimate. No clinical outcome analysis is reported in the registry record.

The record also does not establish that either intervention is safe or unsafe. The adverse-event entries record zero participants at risk, so they cannot be interpreted as evidence that zero participants experienced adverse events. The absence of usable safety counts in the registry record is different from a finding of no harm.

More broadly, a randomized design can support causal comparisons when treatment groups, outcomes, follow-up, and statistical analyses are clearly specified and reported. The design label alone is not a result. To understand clinical effects, readers would need outcome definitions, group-specific clinical results, uncertainty estimates, and information about analysis populations and missing data. Those results are not reported in the registry record. The defensible interpretation is therefore limited to the study framework and appendix enrollment counts.

13. Why This Trial Matters Statistically

This record is statistically notable because it describes a randomized platform protocol while posting an enrollment count as its primary outcome. The distinction between a trial’s design and the information its results actually estimate is important. Randomization is a feature of assignment; it does not by itself make every reported comparison a treatment-effect estimate.

Platform protocols can evaluate multiple interventions and care strategies within a shared research framework. That structure raises statistical questions about which comparisons are intended, how results are compared across appendices, and how multiplicity is addressed. Those details are not reported in the registry record. The record’s sparse results make it especially important not to infer a clinical conclusion from the study’s completed status or from a numerical comparison whose endpoint is enrollment.

For biostatisticians and clinical researchers, the example underscores the need to align endpoint labels, estimands, denominators, and analyses. A count of participants enrolled is useful for describing recruitment. A risk difference for a clinical outcome requires a clinical event definition and a suitable analysis population. When those elements are absent, even an exact-looking estimate and interval can be misread if the quantity is not clinically relevant.

The registry record supports a limited account of study design and recruitment, while leaving clinical efficacy and safety questions unanswered. Recognizing that boundary is an essential part of interpreting trial results responsibly.

14. 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 main limitation of the posted record is that its primary measure is enrollment by appendix rather than a clinical endpoint. Although the protocol description concerns autonomic dysfunction symptoms and related conditions in PASC, no symptom, function, or clinical event result is reported. The registry does not provide clinical comparisons by medication, placebo, or care strategy.

The comparison displayed alongside the enrollment counts is not explained in enough detail to establish its intended statistical interpretation. Its risk-difference label and zero-width interval do not transform enrollment proportions into clinical outcome estimates. No clinical p-value or outcome-specific confidence interval is reported.

Further limitations include the absence of posted secondary outcomes and analyses, and the lack of information about outcome definitions, participant characteristics, follow-up completeness, missing data, adherence, analysis populations, and multiplicity. The record does not report the detailed statistical analysis plan or sample-size justification. The listed adverse-event groups have zero participants at risk, which prevents a meaningful safety interpretation from those entries.

The intervention descriptions are incomplete in the registry record, and the specific roles covered by triple masking are not described. The protocol’s platform structure is apparent, but the details needed to evaluate how treatment comparisons were planned and conducted are not available in the posted results. These limitations constrain interpretation; they do not establish that relevant information was never collected or that the trial lacked additional analyses outside the registry record.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: RECOVER-AUTONOMIC Platform Protocol — NCT06305780.
• Registry record last updated 2026-08-03; status last verified 2026-07.
• Results first posted 2026-08-03.
• 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.

18. Record Summary

RECOVER-AUTONOMIC (NCT06305780) is a completed, randomized, triple-masked, parallel, phase 2 platform protocol for interventions targeting autonomic dysfunction symptoms in PASC. It lists IVIG and ivabradine with placebo and coordinated-care or usual-care combinations. The registry records enrollment of 381 and a primary endpoint of total enrollment by appendix during an enrollment period described as approximately 16 months.

The posted appendix counts are 200 for IVIG and 181 for ivabradine. No clinical outcome analyses or secondary results are posted. The comparison fields associated with the enrollment counts should not be interpreted as clinical treatment effects, and the adverse-event entries do not provide usable safety findings. The registry record therefore describes study design and recruitment but does not report comparative clinical efficacy or safety results.