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 RAS and Coagulopathy in COVID19 (NCT04419610), a randomized early/phase 1 study. The primary outcome is Coagulopathy Associated With COVID-19.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT04419610 |
| Phase | EARLY/Phase 1 |
| Condition | COVID |
| Allocation | Randomized |
| Design model | Single Group |
| Masking | Double |
| Enrollment | 28 |
| Arms in the primary outcome | 2 |
| Lead sponsor | Imperial College London |
| Results posted | Yes |
2. Clinical Question
Population
Patients with confirmed or suspected COVID-19. The registry record gives an enrollment of 28, while the primary outcome is identified as using an incomplete analysis set.
Intervention
The intervention description names TRV027, infused intravenously at 12mg/hr, with treatment continuing until discharge or for 7 days, whichever is sooner. The description also says patients would receive either placebo or TRV027.
Comparator
The other listed group is described as receiving a saline infusion. Sodium chloride 0.9% is named as an intervention in the registry record.
Primary question
The trial aimed to determine whether COVID-19-associated coagulopathy is driven by overactivation of the renin angiotensin system. The posted primary measure is change in D-dimer from Day 1 baseline to Day 3.
This is a mechanistic research question: it concerns a possible relationship between a biological system and changes in a marker associated with coagulation. The primary outcome is not a direct measure of the proposed mechanism itself. It is change in D-dimer, reported in ng/mL FEU, and the registry describes the outcome parameter as a median with a full range. The posted summaries therefore describe the observed distribution of changes in each listed group rather than establishing why those changes occurred.
The registry record identifies the trial as randomized and double-masked, but also labels its model as single-group while listing an intervention group and a no-intervention group. Those design descriptions do not fit together cleanly, and the record does not explain the discrepancy. The clinical question can be stated from the aim and endpoint, but the precise design structure and analysis plan cannot be reconstructed from these labels alone.
3. Trial Design
RAS and Coagulopathy in COVID19, registered as NCT04419610, was sponsored by Imperial College London. The registry record lists an early phase 1 phase, randomized allocation, double masking, and a single-group model. At the same time, it describes two groups: patients given intervention and patients given no intervention. The relationship among these design labels is not explained in the registry record, so they should be read as recorded rather than treated as a fully reconciled design description.
The intervention description specifies an intravenous infusion of either placebo or TRV027 at 12mg/hr, continued until discharge or for 7 days, whichever came sooner. The other group is described as receiving saline infusion, and sodium chloride 0.9% is listed among the interventions. These descriptions do not clarify whether the saline group is the placebo condition referenced in the intervention description. Further details about allocation procedures, masking roles, or treatment administration are not reported in the registry record.
The record lists enrollment as 28. The primary outcome results use an incomplete analysis set and report 11 participants for the intervention group and 10 for the no-intervention group. Safety records separately list 15 participants at risk in the intervention group and 13 in the no-intervention group. The registry record does not explain the differences among the enrollment, outcome, and safety counts, or describe the reasons participants were absent from the primary analysis.
The trial is marked completed. Its recorded start date is 2020-10-09, and its primary completion date is 2021-05-12. The registry lists 15 outcome measures, including secondary outcomes concerning coagulation, RAS, haemolysis, and inflammation. Fourteen secondary outcomes are posted. No analysis entries are listed in the registry record, and details of the protocol, sample-size justification, allocation implementation, or analysis procedures are not reported there.
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.
Overall Study
| Stage | Patients With Confirmed/Suspected C19 Given Intervention | Patients With Confirmed/Suspected C19 Given no Intervention |
|---|---|---|
| STARTED | 15 | 13 |
| COMPLETED | 10 | 11 |
| NOT COMPLETED | 5 | 2 |
Reasons for not completing this period:
| Reason | Patients With Confirmed/Suspected C19 Given Intervention | Patients With Confirmed/Suspected C19 Given no Intervention |
|---|---|---|
| Withdrawal by Subject | 3 | 1 |
| Adverse Event | 1 | 0 |
| discharged early | 1 | 1 |
Analysis population for the primary outcome, as defined in the registry: Incomplete analysis set
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.
| Characteristic | Unit | Patients With Confirmed/Suspected C19 Given Intervention | Patients With Confirmed/Suspected C19 Given no Intervention | Total |
|---|---|---|---|---|
| Participants analysed | 15 | 13 | 28 | |
| Age, Continuous | years | 67 (47 to 89) | 70 (43 to 79) | 68.5 (43 to 89) |
| Sex: Female, Male: Female | Participants | 7 | 9 | 16 |
| Sex: Female, Male: Male | Participants | 8 | 4 | 12 |
| Race/Ethnicity, Customized: white | Participants | 5 | 2 | 7 |
| Race/Ethnicity, Customized: Mixed | Participants | 1 | 0 | 1 |
| Race/Ethnicity, Customized: Asian | Participants | 0 | 3 | 3 |
| Race/Ethnicity, Customized: Black | Participants | 0 | 2 | 2 |
| Race/Ethnicity, Customized: Other | Participants | 7 | 5 | 12 |
| Race/Ethnicity, Customized: Not reported | Participants | 2 | 1 | 3 |
| Region of Enrollment: United Kingdom | Participants | 15 | 13 | 28 |
6. Primary Endpoint
The registry lists the primary outcome as Coagulopathy Associated With COVID-19, measured over Day 1 (baseline) and Day 3)..
| Element | Registry entry |
|---|---|
| Result type | Median |
| Measure of spread | Full Range |
| Unit | ng/mL FEU |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint is change in D-dimer levels from Day 1 baseline to Day 3, with results expressed in ng/mL FEU. D-dimer is a marker related to the formation and breakdown of blood clots. In this trial, it was selected as a measurable indicator relevant to the stated question about COVID-19-associated coagulopathy. The registry record does not report why this specific measure or time point was selected, nor does it provide a threshold defining a clinically important change.
The outcome is reported as a median and full range for each listed group. The posted median change is -313.0 for the intervention group, with a full range from -1253.0 to 822.0. For the no-intervention group, the posted median change is -129.5, with a full range from -365.0 to 710.0. Negative values indicate decreases in D-dimer from baseline under the outcome’s change convention; the full ranges also include positive values in both groups. These summaries describe the recorded changes, but do not by themselves establish a between-group effect.
The record identifies the analysis population as incomplete. It does not provide a confidence interval, a test statistic, or a p-value for the primary outcome. The endpoint therefore offers descriptive information about the observed changes in the analyzed participants, while leaving the precision and inferential comparison between groups unreported in the registry record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The primary outcome is presented as a median change from baseline to Day 3, not as a mean change or a modeled treatment contrast. The intervention group’s median change is -313.0 ng/mL FEU, with a full range from -1253.0 to 822.0. The no-intervention group’s median change is -129.5 ng/mL FEU, with a full range from -365.0 to 710.0. Both full ranges extend across negative and positive changes. Thus, the posted summaries show variation in direction and magnitude among participants in each group.
A median describes the central position of the observed values and is less influenced by extreme values than a mean. It does not convey the entire distribution. The full range reports the smallest and largest recorded values, but does not show how frequently values occurred between those limits. The broad ranges and the incomplete analysis set are important context when reading the medians. They do not, on their own, establish why participants’ values changed or whether any difference between the groups is reliably distinguishable from chance variation.
The registry record gives no inferential result for the primary outcome: no confidence interval, p-value, or formal between-group estimate is posted. Without such information, the degree of statistical precision around the group summaries is not quantified. It is also not possible to determine from these summaries alone whether the observed contrast is compatible with a wide range of underlying effects. The registry record does not report an analysis plan that would clarify whether the primary comparison was intended to be adjusted, unadjusted, or based on another approach.
The outcome counts differ from the enrollment count, and the record explicitly characterizes the primary analysis population as incomplete. It does not explain which participants contributed to the primary endpoint, why other enrolled participants were not included, or how missing Day 3 measurements were handled. These omissions limit assessment of possible selection effects and of how closely the analyzed participants represent those enrolled.
The stated purpose was to investigate whether coagulopathy associated with COVID-19 is driven by overactivation of the renin angiotensin system. The endpoint is a coagulation-related marker, not a direct measurement of the complete proposed causal pathway. The record lists additional outcomes involving RAS and other biological markers, but does not post their analysis results in the registry record. The primary D-dimer summaries therefore address one part of the research question and should not be read as a demonstration of the underlying mechanism.
Overall, the registry record gives descriptive group medians and ranges for Day 3 D-dimer change. It does not provide enough inferential or analysis detail to quantify a treatment contrast or its uncertainty. The reported values are observations from an incomplete analysis set, not a stand-alone basis for a causal conclusion.
9. Statistical Methods Explained
The primary outcome uses a change score: the Day 3 D-dimer value is compared with the Day 1 baseline value for each participant. A change score is intended to express how a measure moved over time within participants. Its interpretation depends on the direction convention used in the analysis; the registry describes the measure as change from baseline and reports negative and positive values. The record does not give further computational details for the change score.
Why report a median?
A median is the middle value after observations are ordered. It describes the center of the observed values without requiring the distribution to be symmetric. In general, medians can be useful when data are skewed or include extreme observations. The registry explicitly identifies the primary outcome parameter as a median, but does not state why that summary was selected or describe the distribution of individual values. The median is a summary of the analyzed participants; it is not an estimate of every participant’s response.
What does the full range add?
The full range gives the lowest and highest observed values. Here, the intervention group’s range runs from -1253.0 to 822.0, and the no-intervention group’s range runs from -365.0 to 710.0. In general, a range can make the extent of observed variation visible, but it is sensitive to the most extreme observations and does not describe the density or shape of the values between endpoints. A range is not a confidence interval. It does not quantify uncertainty about the population median or a between-group effect.
What would a confidence interval contribute?
In general, a confidence interval gives a range of estimates compatible with a statistical procedure applied to the observed data. It helps communicate precision around an estimate; narrower intervals indicate greater precision under the method’s assumptions, while wider intervals indicate less. No confidence interval for the primary outcome is reported in the registry record. Consequently, the precision of the medians or of a contrast between groups cannot be assessed from an interval estimate.
What can be concluded from comparing these summaries?
Comparing medians can describe how the central observed changes differ, but a difference between two descriptive summaries is not automatically a formal treatment-effect estimate. A formal comparison would need a defined estimand and an analysis method, along with information about uncertainty. The registry record does not post a primary-outcome test, a model, or a contrast estimate. No recalculated comparison is reported in the registry record. The displayed group summaries should therefore be read descriptively, not as a substitute for an inferential analysis.
Why do analysis populations matter?
The primary outcome is labeled as using an incomplete analysis set. In general, an analysis population defines which participants are included in a particular result. Different choices can affect the interpretation, especially when participants lack outcome measurements or do not follow the assigned treatment. The registry record does not explain the incomplete-set definition, the number excluded from the primary analysis, or the handling of missing measurements. The result cannot therefore be interpreted as an analysis of all enrolled participants without additional information.
How should the design labels be understood?
The registry record identifies randomized allocation and double masking, while also labeling the model single-group and listing two groups with different infusion descriptions. Randomization generally aims to make treatment groups comparable in expectation, and masking generally limits the influence of knowledge about assignment. These are general design concepts, not evidence about how well those procedures were implemented in this trial. The record does not describe the randomization sequence, allocation concealment, who was masked, or whether masking was maintained. The inconsistent model and group descriptions also prevent a confident reconstruction of the intended design from registry labels alone.
What does over-dispersion mean in general?
For count outcomes, over-dispersion means that observed variability exceeds what a particular simple statistical model assumes. A model that ignores over-dispersion can produce uncertainty estimates that are too small. This is a general concept and is not a reported finding about the D-dimer endpoint. The primary endpoint is summarized as a median and full range, and the registry record does not report a model or a dispersion assessment. It would therefore be inappropriate to infer that over-dispersion was present or that a specific adjustment was used.
Were sample-size and testing choices documented?
The registry record does not report the trial’s sample-size justification, planned statistical tests, interim analyses, or multiplicity procedure. The record lists 15 outcome measures and 14 posted secondary outcomes, but does not explain how those outcomes were prioritized or how multiple comparisons were addressed. In general, a prespecified analysis plan helps distinguish confirmatory analyses from exploratory ones and clarifies how uncertainty and multiple testing are handled. Without that information, the primary result can be described, but the intended inferential framework cannot be verified.
10. Multiplicity, Missing Data and Analysis Populations
The registry record lists 15 outcome measures and 14 posted secondary outcomes. These include outcomes concerning coagulation-system markers, changes in such markers, RAS markers, and haemolysis or inflammation. The primary endpoint is change in D-dimer from baseline to Day 3. The record does not report a multiplicity procedure or explain how the primary and secondary outcomes were prioritized for statistical testing. In general, examining multiple outcomes can increase the chance of at least one apparently unusual result when many tests are conducted. Whether and how that issue was handled is not reported in the registry record.
No analysis entries are listed. The record does not report an analysis plan, interim analyses, a sample-size justification, or statistical tests for the primary outcome. These omissions mean that the intended inferential procedures and any prespecified hierarchy of outcomes cannot be checked against the posted summaries. The record’s sample-size assumptions for planning illustrations are not a substitute for a trial-specific sample-size justification or an account of the trial’s planned analysis.
The primary analysis population is explicitly described as incomplete. The outcome groups report 11 and 10 participants, while enrollment is listed as 28 and the safety groups list 15 and 13 participants at risk. The record does not explain these differences, define the incomplete analysis set, or say how missing baseline or Day 3 measurements were handled. It also does not report whether missing data were imputed, excluded, or handled by another method. These details matter because missingness can affect which participants are represented in the endpoint summaries and can influence the interpretation of group comparisons.
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 |
|---|---|---|---|
| Patients With Confirmed/Suspected C19 Given Intervention | 5 | 15 | 33.3% |
| Patients With Confirmed/Suspected C19 Given no Intervention | 3 | 13 | 23.1% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Patients With Confirmed/Suspected C19 Given Intervention | 2 of 15 |
| Patients With Confirmed/Suspected C19 Given no Intervention | 1 of 13 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 0% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Patients With Confirmed/Suspected C19 Given Intervention | 3 of 15 |
| Patients With Confirmed/Suspected C19 Given no Intervention | 1 of 13 |
Most frequent serious adverse event terms
| Event term | Organ system | Patients With Confirmed/Suspected C19 Given Intervention | Patients With Confirmed/Suspected C19 Given no Intervention |
|---|---|---|---|
| severe COVID 19 pneumonia | Respiratory, thoracic and mediastinal disorders | 2 of 15 | 1 of 13 |
| pulmonary embolism | Respiratory, thoracic and mediastinal disorders | 1 of 15 | 1 of 13 |
| confusion | Nervous system disorders | 1 of 15 | 0 of 13 |
| Bacterial Sepsis | Infections and infestations | 0 of 15 | 1 of 13 |
| Hypotension | Vascular disorders | 1 of 15 | 0 of 13 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Patients With Confirmed/Suspected C19 Given Intervention | Patients With Confirmed/Suspected C19 Given no Intervention |
|---|---|---|---|
| Infection | Infections and infestations | 2 of 15 | 1 of 13 |
| Epistaxis | Blood and lymphatic system disorders | 1 of 15 | 0 of 13 |
| injection site reaction | Surgical and medical procedures | 0 of 15 | 1 of 13 |
Serious events with the highest arm-level rate: severe covid 19 pneumonia (13.3%), pulmonary embolism (7.7%), bacterial sepsis (7.7%), confusion (6.7%), hypotension (6.7%).
The safety record lists participants at risk and participants affected for serious and other adverse events, along with deaths. For the intervention group, 15 participants were at risk for serious adverse events and 5 were affected; 15 were at risk for other adverse events and 3 were affected; deaths are listed as 2. For the no-intervention group, 13 participants were at risk for serious adverse events and 3 were affected; 13 were at risk for other adverse events and 1 was affected; deaths are listed as 1. These are the posted counts, and they should be kept distinct from the primary outcome analysis counts.
The record also lists serious adverse event terms with percentages: severe COVID 19 pneumonia at 13.3%, pulmonary embolism at 7.7%, Bacterial Sepsis at 7.7%, confusion at 6.7%, and Hypotension at 6.7%. The registry record does not specify in this listing which group or denominator corresponds to each percentage, or whether the terms represent unique participants or event occurrences. The percentages should therefore be read as posted descriptors, not as a directly comparable group-specific risk estimate.
Counts and percentages alone do not establish that an intervention caused or prevented an event. The registry record does not provide event timing, severity details beyond the serious-event classification, or an adjusted safety comparison. These figures describe recorded safety information and should not be interpreted as a causal estimate.
12. What the Result Does, and Does Not, Mean
The result establishes what the registry record reports for the primary endpoint: median D-dimer change from Day 1 baseline to Day 3 was -313.0 ng/mL FEU in the intervention group and -129.5 ng/mL FEU in the no-intervention group. The full ranges were -1253.0 to 822.0 and -365.0 to 710.0, respectively. These are descriptive summaries for the incomplete analysis set identified in the record. They show that participant-level changes varied, including both negative and positive values in each group.
The result does not, by itself, establish a statistically precise difference between groups. The registry record does not report a confidence interval, p-value, or formal primary-outcome contrast. It also does not document how missing outcome measurements were handled or explain the incomplete analysis population. Thus, the summaries cannot establish how much uncertainty surrounds the observed group values or how sensitive they might be to the participants included.
The endpoint is relevant to coagulopathy, but it is not a direct demonstration that renin angiotensin system overactivation caused the coagulopathy. The trial’s stated objective concerns a possible mechanism, while the posted primary result is a change in D-dimer. A marker’s movement alone does not verify a causal pathway. The registry record lists other biological outcomes, but their analyses and results are not reported in the registry record.
The trial is recorded as randomized and double-masked, but also as single-group despite having two group descriptions. The record does not resolve that inconsistency or provide operational details of randomization and masking. Accordingly, those design labels should not be used to infer more about implementation than the record documents.
The most defensible reading is narrow: the record reports two group medians and full ranges for Day 3 change in D-dimer, along with incomplete analysis and safety counts. It does not provide the statistical uncertainty or analysis detail needed to make a firm comparative or mechanistic interpretation. These results are not a basis for medical advice.
13. Why This Trial Matters Statistically
This trial is statistically informative as an example of why the estimand, analysis population, and uncertainty estimate matter alongside a numeric endpoint summary. The primary outcome has a clearly named marker and measurement interval: change in D-dimer from Day 1 baseline to Day 3. Yet the record reports medians and ranges without a confidence interval or formal comparison. Readers can describe the posted distributions, but cannot infer the precision of a treatment contrast from the medians alone.
The record also illustrates how registry design fields and arm descriptions need to be read together. Randomized allocation and double masking are listed, but the model is labeled single-group while the results and descriptions identify two groups. Since the record does not reconcile these entries, interpretation requires acknowledging that design uncertainty rather than silently choosing one field as definitive.
Counts from different parts of a record can refer to different analysis contexts. Here, enrollment, primary outcome group counts, and safety denominators are all reported, but their relationship is not explained. The primary outcome is labeled as based on an incomplete analysis set. That makes transparent reporting of participant flow and missing-data handling particularly important for interpreting whether the analyzed sample represents the intended trial population.
Finally, the trial’s mechanistic aim and its endpoint are related but not identical. A coagulation marker can contribute evidence about the stated question, yet a marker summary does not establish a causal biological mechanism. Clear reporting of planned analyses, uncertainty, and the connection between mechanistic outcomes would be needed to support stronger interpretation. The record offers a useful descriptive starting point while leaving these statistical questions unresolved.
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 result is based on an incomplete analysis set, but the registry record does not define that set or explain why the outcome group counts are smaller than the enrollment count. It does not describe participant flow, exclusions, missing Day 3 measurements, or the approach used for missing data. These gaps make it difficult to judge the representativeness of the analyzed participants.
The design is not fully clear from the registry fields. Randomized allocation and double masking are listed, but the model is labeled single-group and the record contains two group descriptions. It does not report the randomization method, allocation concealment, masking roles, or whether masking was maintained. The relation between the placebo language, TRV027 infusion, and saline group is also not fully specified.
The primary endpoint is described as median change with a full range, but no confidence interval, p-value, formal group contrast, or statistical model is reported. The registry record does not state why the median was selected, define a clinically important change, or document a sample-size justification. It also does not describe interim analyses, multiplicity control, or a prespecified statistical analysis plan.
Although 15 outcomes are listed and 14 secondary outcomes are posted, their results and analyses are not included in the registry record. The record also does not clarify the denominator or group attribution for the listed serious-event percentages. These specific reporting gaps limit both comparative interpretation and assessment of the proposed biological pathway.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: RAS and Coagulopathy in COVID19 — NCT04419610.
- Registry record last updated 2024-05-03; status last verified 2024-05.
- Results first posted 2024-05-01.
- 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
NCT04419610, titled RAS and Coagulopathy in COVID19, is sponsored by Imperial College London and is marked completed. The registry lists an early phase 1 study, randomized allocation, double masking, and a single-group model. Its enrollment is 28, with a recorded start date of 2020-10-09 and primary completion date of 2021-05-12.
The stated objective was to determine whether COVID-19-associated coagulopathy is driven by overactivation of the renin angiotensin system. The primary endpoint is change in D-dimer from Day 1 baseline to Day 3, reported as median and full range in ng/mL FEU. The intervention group median is -313.0, with a range from -1253.0 to 822.0; the no-intervention group median is -129.5, with a range from -365.0 to 710.0. The primary analysis population is described as incomplete.
The record lists 15 outcome measures, 14 posted secondary outcomes, and no analysis entries. It does not report a primary-outcome confidence interval or formal comparison, or explain the incomplete analysis set. Its group and model descriptions are not fully consistent, and that discrepancy is not resolved in the registry record.