This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for Safety Study of Intranasal Etripamil for the Termination of Spontaneous Episodes of Paroxysmal Supraventricular Tachycardia (PSVT). NODE-302 (NCT03635996), a na phase 3 study. The primary outcome is Time to Conversion of an Episode of PSVT to Sinus Rhythm (SR) After Study Drug Administration..
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT03635996 |
| Phase | Phase 3 |
| Condition | Paroxysmal Supraventricular Tachycardia |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 169 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Milestone Pharmaceuticals Inc. |
| Results posted | Yes |
2. Clinical Question
Population
People with paroxysmal supraventricular tachycardia (PSVT) who experienced a spontaneous episode. The study enrolled 169 participants. For the primary efficacy analysis, the registry record identifies 92 patients whose PSVT episode was confirmed by adjudication and treated with etripamil nasal spray 70 mg. These figures describe different aspects of the study record and should not be treated as interchangeable analysis populations.
Intervention
Etripamil nasal spray 70 mg, self-administered by patients during a PSVT episode in an outpatient setting without medical supervision. The listed intervention also includes the Aptar Pharma Nasal Spray Bidose System. The record describes the dose to be evaluated as 70 mg.
Comparator
There was no randomized comparator group: the study is recorded as single-group, with allocation marked NA and no masking. The record therefore does not describe a like-for-like control arm for estimating a comparative treatment effect.
Primary question
The listed primary endpoint concerns time, in minutes, from study-drug administration to conversion of a PSVT episode to sinus rhythm (SR). The study description states that its primary objective was to evaluate safety when etripamil was self-administered in an outpatient setting. The endpoint description also calls the time-to-conversion measure the primary efficacy variable. The numerical endpoint result is not reported in the registry record, so the record does not establish the observed time to conversion or its precision.
3. Trial Design
NCT03635996, titled NODE-302, is recorded as a Phase 3, multicentre, open-label safety study of etripamil nasal spray in spontaneous PSVT episodes. Its official title describes it as an extension of NODE-301. The registry classifies the model as single-group, allocation as NA, and masking as none. Thus, the record describes treatment and outcome observation without a randomized comparison arm or masking.
The study intervention was etripamil nasal spray 70 mg. The listed device was the Aptar Pharma Nasal Spray Bidose System. The brief study description says patients would self-administer the spray during an episode in an outpatient setting, without medical supervision. The enrollment figure is 169. The record gives a study start date of 2018-12-10, a primary completion date of 2020-11-13, and a status of terminated. A reason for termination is not reported in the registry record.
The primary endpoint entry is time to conversion of a PSVT episode to SR after study-drug administration, measured in minutes over a timeframe of 18 months. The endpoint description refers to an efficacy population and specifies the first PSVT episode for each patient that was confirmed by adjudication and treated with etripamil 70 mg. It states that 92 patients met that description and were included in the primary analysis. The brief summary, however, describes the primary objective as evaluation of safety. The record does not explain this difference between the stated study objective and the listed primary efficacy endpoint.
Because the study has no randomized control group, its design can describe observed outcomes among treated participants but does not support a randomized between-group estimate. The record does not report a protocol rationale for the design, an explanation for the termination, or additional details about the conduct of the study.
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: Of the 169 patients enrolled, 64 (37.9%) of 169 patients did not treat an episode with etripamil in this study.
Overall Study
| Stage | Etripamil NS 70 mg |
|---|---|
| STARTED | 169 |
| Patients Not Treated With Etripamil | 64 |
| Safety Population | 105 |
| Efficacy Population | 92 |
| COMPLETED | 2 |
| NOT COMPLETED | 167 |
Reasons for not completing this period:
| Reason | Etripamil NS 70 mg |
|---|---|
| Study terminated by Sponsor | 94 |
| Withdrawal by Subject | 20 |
| Ablation | 26 |
| Adverse Event | 7 |
| Physician Decision | 3 |
| Prohibited medication | 5 |
| Did not meet eligibility criteria | 5 |
| Site closure (2), compliance with IP, directed by sponsor and site termination. | 5 |
| Protocol Violation | 1 |
| Lost to Follow-up | 1 |
Analysis population for the primary outcome, as defined in the registry: Primary analysis of the primary efficacy endpoint for each patient's first episode of PSVT confirmed by adjudication and treated with etripamil NS 70 mg. There were 92 patients who had a PSVT episode that was confirmed by adjudication and were included in the primary analysis.
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.
Population: Safety population
| Characteristic | Unit | Etripamil NS 70 mg |
|---|---|---|
| Participants analysed | 105 | |
| Age, Continuous: Age at informed consent signed | years | 58 (SD 13.75) |
| Age, Continuous: Age at confirmation of PSVT | years | 57.2 (SD 13.79) |
| Sex: Female, Male: Female | Participants | 65 |
| Sex: Female, Male: Male | Participants | 40 |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | 1 |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | 100 |
| Ethnicity (NIH/OMB): Unknown or Not Reported | Participants | 4 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 |
| Race (NIH/OMB): Asian | Participants | 3 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 2 |
| Race (NIH/OMB): Black or African American | Participants | 8 |
| Race (NIH/OMB): White | Participants | 87 |
| Race (NIH/OMB): More than one race | Participants | 5 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 0 |
| PSVT confirmation duration (years) | years | 1.3 (SD 1.73) |
| Number of patient-reported PSVT episodes in the year prior to NODE-301 | episodes | 9.7 (SD 11.79) |
| Number of patient-reported emergency department visits for PSVT in lifetime | emergency department visits | 2.7 (SD 2.74) |
6. Primary Endpoint
The registry lists the primary outcome as Time to Conversion of an Episode of PSVT to Sinus Rhythm (SR) After Study Drug Administration., measured over 18 months.
| Element | Registry entry |
|---|---|
| Result type | Median |
| Measure of spread | 95% Confidence Interval |
| Unit | minutes |
| Endpoint classification | not reduced to a single comparison |
The listed primary endpoint is the time from study-drug administration to conversion of a PSVT episode to sinus rhythm. Time is expressed in minutes, and the registry identifies the summary measure as a median with a 95% confidence interval. The timeframe is 18 months. The endpoint description specifies the first episode for each patient that was confirmed by adjudication and treated with etripamil nasal spray 70 mg; 92 patients are reported as included in this primary analysis.
In general, a time-to-event endpoint captures how long it takes for a defined event to occur, rather than only whether it occurred. Here, the event is conversion to SR. A median can describe the midpoint of the observed time distribution, while a confidence interval conveys uncertainty around the estimated median. These summaries address the timing of conversion in the analysis population; they do not, on their own, compare that timing with an untreated or alternative-treatment group.
The numerical median and its confidence interval are not reported in the registry record. The record therefore identifies what was to be measured and how it was to be summarized, but does not report the estimated time to conversion or the precision of that estimate.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record describes a single-group study of etripamil nasal spray 70 mg for spontaneous PSVT episodes. Its listed primary endpoint is the time from drug administration to conversion to SR, summarized by a median and 95% confidence interval. The endpoint analysis is described as involving 92 patients whose first treated episode was confirmed by adjudication. Although the record provides this definition and analysis population, it does not report the median, confidence interval, or another numerical result for the endpoint.
That omission limits interpretation of efficacy. Without the estimate, readers cannot determine the observed time-to-conversion distribution from the registry record or assess the precision of the median. Without a reported confidence interval, the uncertainty around the endpoint estimate also cannot be evaluated. These are absences in the registry record, not evidence that conversion did or did not occur within a particular time.
The design also sets a boundary on what can be concluded. A single-group, open-label study without a randomized comparator can report outcomes observed after use of the intervention, but it cannot provide a randomized contrast against another treatment or a control condition. Even if an outcome estimate were reported, an observed time-to-conversion result alone would not establish how that timing compares with what would have happened under another condition.
The record includes safety counts for the etripamil group: 8 serious adverse events among 105 at risk, 67 other adverse events among 105 at risk, and 0 deaths. It also lists serious adverse event terms with percentages, including supraventricular tachycardia at 2.9%, and bradycardia, ataxia, syncope, pancreatitis, and troponin increased at 1.0% each. These entries describe the posted safety data. They do not by themselves establish that the study drug caused an event, nor do they provide a randomized comparison for judging differences in risk.
The record states that the study was terminated, but the reason is not reported in the registry record. Termination alone does not reveal whether the study stopped for safety, operational, recruitment, efficacy, or another reason. No inference about the reason or its consequences should be made from status alone. In particular, the missing endpoint estimate and the absence of a control group leave the primary efficacy question unresolved by the registry information.
Overall, the record offers design details, the endpoint definition, an analysis population, and selected safety counts. It does not report the primary endpoint result, a comparative estimate, or the reason for termination. Interpretation should remain confined to those documented features.
9. Statistical Methods Explained
The statistical methods that can be described from the registry record are limited. It identifies a median and 95% confidence interval as the summary for the primary time-to-conversion endpoint, and defines an analysis population based on patients’ first adjudication-confirmed, treated PSVT episode. It does not report a detailed statistical analysis plan, a numerical endpoint estimate, or the interval limits. General statistical explanations below describe what these methods mean; they are not claims about additional procedures used in this trial.
What does a median time represent?
In general, the median is the middle of an ordered distribution. For a time-to-event outcome, it describes the time by which half of the relevant observations have reached the defined event, subject to the analysis method and the available follow-up. Here, the defined event is conversion from PSVT to SR after study-drug administration. A median focuses on the central part of the time distribution and is less influenced by unusually long or short observations than an arithmetic mean can be.
The registry record does not state the estimated median. It also does not report the number of episodes with observed conversion, whether any observations were censored, or the specific calculation method. Therefore, the endpoint definition should not be mistaken for a reported result.
What does a confidence interval add?
In general, a confidence interval expresses uncertainty in an estimate under the assumptions of the statistical method used. A narrower interval indicates greater precision than a wider interval, while neither width nor location can be judged without the interval itself. The record names a 95% confidence interval for the median but does not report its numerical limits. No conclusion about precision or compatibility with particular values can be drawn from the confidence level alone.
A confidence interval is not a guarantee that the true value lies within the reported bounds, nor does its confidence level describe the chance that an individual patient will experience a particular time. It is a statistical summary of uncertainty around an estimated quantity. Since the estimate and interval are absent from the registry record, that uncertainty cannot be assessed for this endpoint.
Why does the analysis population matter?
The primary endpoint population is defined as each patient’s first PSVT episode that was confirmed by adjudication and treated with etripamil 70 mg. The record states that 92 patients were included. Restricting an analysis to episodes confirmed by adjudication can make the outcome definition more consistent, because the classification of PSVT is subject to confirmation. It also means the endpoint result would describe the specified analysis population, rather than automatically describing every enrolled participant or every episode.
The registry record does not provide further detail about adjudication procedures, episode eligibility, or how missing endpoint observations were handled. It does not identify an intention-to-treat analysis for this endpoint. Those details are important when judging how the analyzed population relates to enrollment and whether exclusions or missing observations could affect the estimate.
What can a single-group estimate show?
In general, a single-group study can estimate outcomes observed among participants who receive the study intervention. It cannot create the randomized counterfactual comparison that would show how outcomes differ under an alternative assigned condition. In this study, the record lists no randomized comparator, and the design is open-label. Consequently, an observed time-to-conversion estimate, if reported, would be descriptive of the analyzed treated episodes rather than a randomized estimate of comparative effect.
Open-label conduct means masking is recorded as none. In general, knowledge of treatment can influence reporting, assessment, or other aspects of outcome collection, although the endpoint uses adjudication confirmation. The record does not provide details that would establish how these possibilities were addressed. No claim about the size or direction of any such influence can be made from the design label alone.
How should the planning assumptions be read?
The registry record describes a planning illustration based on an observed effect, with two-sided significance level 0.05, equal allocation between two arms, and a normal approximation. The effect to detect is described as a stated fraction of the observed effect. For time-to-event planning, the stated output is a total number of events using the Schoenfeld method; other planning outputs are participants per arm. These are hypothetical planning assumptions, not evidence that this single-group trial used a two-arm design or those assumptions in its own protocol.
In general, sample-size planning asks how much information a future comparison might need under chosen assumptions about effect size, error rate, allocation, and analysis. Such calculations are conditional on those assumptions. They are not observed power, and they do not demonstrate that a study was adequately powered after the fact. The planning values themselves are not reported in the registry record, and the record does not report a protocol-based sample-size justification. The observed effect used for the illustration is also not stated in the registry record, so the planning assumptions cannot be independently interpreted from the posted information.
More broadly, statistical significance, effect magnitude, and precision are distinct concepts. A significance level is a rule used in a testing procedure; an effect estimate describes the observed magnitude; and a confidence interval conveys uncertainty. The registry record does not provide the numerical primary endpoint result or a hypothesis-test result. Accordingly, no statistical significance claim for the endpoint can be made from the information recorded.
10. Multiplicity, Missing Data and Analysis Populations
The registry record identifies one outcome measure and no analyses. It names the time to conversion of a PSVT episode to SR as the primary endpoint, but does not report a numerical estimate or a statistical test. The analysis plan, including any prespecified hypothesis tests or adjustment for multiple comparisons, is not reported in the registry record. It is therefore not possible to determine whether multiplicity was addressed or whether additional analyses were planned.
Multiplicity arises in general when several outcomes, time points, subgroups, or statistical tests are examined. Without an analysis plan, readers cannot assess how the study distinguished confirmatory analyses from exploratory ones or whether repeated testing affected interpretation. The fact that one outcome measure is listed does not establish that no other analyses were conducted; the record reports zero analyses in its analysis listing, and further analytical detail is not reported in the registry record.
The primary endpoint population is described as 92 patients with a first episode confirmed by adjudication and treated with etripamil 70 mg. The registry does not report how missing outcome data were handled, whether any participants or episodes lacked evaluable endpoint information, or whether sensitivity analyses were used. These omissions matter because missingness and eligibility decisions can affect which observations contribute to an estimate and how broadly that estimate applies.
The record also does not describe additional analysis populations beyond the efficacy population named for the primary endpoint. It does not report whether analyses included all enrolled participants, how safety populations were defined, or how deviations from the intended treatment procedure were handled. Those details are not reported in the registry record and should not be inferred from the endpoint population description.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| Etripamil NS 70 mg | 8 | 105 | 7.6% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Etripamil NS 70 mg | 0 of 105 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 1% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Etripamil NS 70 mg | 67 of 105 |
Most frequent serious adverse event terms
| Event term | Organ system | Etripamil NS 70 mg |
|---|---|---|
| Supraventricular tachycardia | Cardiac disorders | 3 of 105 |
| Bradycardia | Cardiac disorders | 1 of 105 |
| Ataxia | Nervous system disorders | 1 of 105 |
| Syncope | Nervous system disorders | 1 of 105 |
| Pancreatitis | Gastrointestinal disorders | 1 of 105 |
| Troponin increased | Investigations | 1 of 105 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Etripamil NS 70 mg |
|---|---|---|
| Nasal discomfort | Respiratory, thoracic and mediastinal disorders | 23 of 105 |
| Nasal congestion | Respiratory, thoracic and mediastinal disorders | 17 of 105 |
| Rhinorrhea | Respiratory, thoracic and mediastinal disorders | 16 of 105 |
| Epistaxis | Respiratory, thoracic and mediastinal disorders | 5 of 105 |
| Sneezing | Respiratory, thoracic and mediastinal disorders | 5 of 105 |
| Headache | Nervous system disorders | 5 of 105 |
| Mucosal hypertrophy | General disorders | 5 of 105 |
| Dizziness | Nervous system disorders | 4 of 105 |
| Throat irritation | Respiratory, thoracic and mediastinal disorders | 4 of 105 |
| Lacrimation increased | Eye disorders | 3 of 105 |
Serious events with the highest arm-level rate: supraventricular tachycardia (2.9%), bradycardia (1.0%), ataxia (1.0%), syncope (1.0%), pancreatitis (1.0%).
The safety record lists 8 serious adverse events among 105 at risk in the etripamil nasal spray 70 mg group. It lists 67 other adverse events among 105 at risk and 0 deaths. The serious adverse event terms with the highest listed percentages are supraventricular tachycardia at 2.9%, bradycardia at 1.0%, ataxia at 1.0%, syncope at 1.0%, pancreatitis at 1.0%, and troponin increased at 1.0%.
These counts and term percentages are descriptive registry entries. They should not be read as a comparison with an untreated group, since the study is recorded as single-group and has no randomized comparator. The record does not provide further information about event timing, duration, severity beyond the serious-event classification, or individual-level overlap between event categories. The listed percentages should therefore be interpreted as reported, without deriving additional rates or totals.
An adverse event occurring during a study does not, by itself, establish that the intervention caused it. A causal assessment would require information beyond these counts, including suitable comparative evidence and clinical evaluation. The registry record does not report a causal attribution analysis for these events.
12. What the Result Does, and Does Not, Mean
The record establishes that NODE-302 was a Phase 3, open-label, single-group study of etripamil nasal spray 70 mg for spontaneous PSVT episodes. It also identifies the intended outpatient, self-administration setting and defines the primary time-to-conversion endpoint. For the primary efficacy analysis, it reports 92 patients with a first adjudication-confirmed episode treated with etripamil 70 mg. These registry entries clarify the study question and the population to which the stated endpoint analysis pertains.
What the record does not establish is the observed median time to conversion or its 95% confidence interval. Although those are the named summary measure and dispersion, the numerical estimate is not reported in the registry record. As a result, the posted information does not establish the magnitude or precision of the endpoint result. It also does not provide a randomized comparison that could estimate how outcomes differ from another treatment or a control condition.
The stated safety objective and the listed primary efficacy endpoint describe different facets of the record. The brief summary says the primary objective was to evaluate safety during outpatient self-administration, while the endpoint entry identifies time to conversion as the primary efficacy variable. The registry does not explain this distinction. The available serious and other adverse event counts describe reported safety data, but do not establish that etripamil caused or prevented any listed event.
The study status is terminated, but the reason is not reported in the registry record. Status alone does not show why the study ended or what bearing termination had on the analyses. The record also does not report a protocol-based sample-size justification, detailed analysis plan, missing-data approach, or multiplicity strategy. Those omissions limit assessment of the planned statistical framework.
Accordingly, the record supports a description of design, endpoint definition, analysis population, and selected safety entries. It does not support a conclusion about the numerical time-to-conversion result, comparative efficacy, or causal interpretation of adverse events. Those boundaries reflect the information recorded and the single-group design, rather than a judgment about the intervention.
13. Why This Trial Matters Statistically
This study raises a useful statistical distinction between defining an endpoint and reporting its result. The registry record specifies a clinically interpretable event—conversion of PSVT to SR—and a time scale in minutes. It also identifies a median and 95% confidence interval as the intended summary. Yet the numerical estimate and interval are not reported in the registry record. A precise endpoint definition is valuable, but without the result it cannot answer how long conversion took in the analyzed population or how uncertain that estimate was.
The study also illustrates how design determines the scope of inference. A single-group, open-label study can document outcomes and safety events observed after use of an intervention. It does not provide a randomized comparison for estimating a difference against another assigned condition. This distinction is especially important when interpreting a time-to-event endpoint: an observed time distribution and a comparative treatment effect are different statistical quantities.
Population definition is another key issue. The registry reports 169 enrolled participants and identifies 92 patients in the primary efficacy analysis based on a first episode confirmed by adjudication and treated with etripamil 70 mg. These figures refer to enrollment and a specified endpoint population, respectively. Clear reporting of how participants move from enrollment into each analysis population helps readers assess whom a result describes. Further detail about exclusions and missing outcomes is not reported in the registry record.
Finally, the safety entries show why counts need context. The record reports serious and other adverse events in a single-group study, alongside selected serious-event terms. These observations can describe what was recorded, but without a comparator they cannot by themselves establish excess risk or causation. Statistical interpretation depends not only on the numbers, but also on the design, population, endpoint definition, and completeness of reporting.
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 primary limitation for interpreting the efficacy endpoint is that its numerical median and 95% confidence interval are not reported in the registry record. The endpoint is defined, and the analysis population is described, but the observed estimate and its precision cannot be assessed from the record.
The single-group, open-label design provides no randomized control comparison. Therefore, the record cannot support a randomized estimate of the difference in time to conversion between etripamil and another condition. Masking is recorded as none, and allocation is recorded as NA. The registry does not describe additional procedures that might address potential measurement or reporting influences.
The record reports 169 enrolled participants and 92 patients included in the primary efficacy analysis, but does not explain the full transition between those figures. Details about exclusions, missing endpoint data, and the handling of episodes not confirmed by adjudication are not reported in the registry record. The method used to calculate the median and confidence interval is also not described beyond naming those summaries.
The stated primary objective concerns safety, while the listed primary endpoint is described as a primary efficacy variable. The record does not explain the relationship between those descriptions. Although selected adverse event counts and terms are reported, details on event timing, attribution, and overlap between categories are not provided in the registry record.
The study is marked terminated, but its reason for termination is not reported in the registry record. The statistical analysis plan, missing-data approach, multiplicity strategy, and protocol-based sample-size justification are also not reported. These limitations do not determine what the missing information would show; they mark the boundaries of what can be concluded from the registry record.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Safety Study of Intranasal Etripamil for the Termination of Spontaneous Episodes of Paroxysmal Supraventricular Tachycardia (PSVT). NODE-302 — NCT03635996.
- Registry record last updated 2024-11-05; status last verified 2021-03.
- Results first posted 2023-04-24.
- 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.
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18. Record Summary
NCT03635996, NODE-302, is recorded as a Phase 3, multicentre, open-label, single-group study of etripamil nasal spray 70 mg for spontaneous PSVT episodes. The official title describes it as an extension of NODE-301. The study was intended to evaluate safety during outpatient self-administration without medical supervision. The record lists the Aptar Pharma Nasal Spray Bidose System as a device intervention.
Enrollment was 169. The registry lists a start date of 2018-12-10, primary completion on 2020-11-13, and status as terminated. The primary endpoint is time to conversion to SR, summarized as a median with a 95% confidence interval over 18 months. The primary analysis population is described as 92 patients with a first adjudication-confirmed, treated episode. The endpoint estimate and confidence interval, reason for termination, and detailed analysis plan are not reported in the registry record.
The safety listing reports 8 serious adverse events and 67 other adverse events among 105 at risk, with 0 deaths. The design has no randomized comparator, so these entries are descriptive rather than comparative.