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 Double Blind Combination of Rituximab by Intravenous and Intrathecal Injection Versus Placebo in Patients With Low-Inflammatory Secondary Progressive Multiple Sclerosis (RIVITaLISe) (NCT01212094), a randomized phase 1, phase 2 study. The primary outcome is Analysis of Changes in CSF CXCL13 Induced by Active Treatment (Rituximab) Measured 3 Months After 1st Drug Administration.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01212094 |
| Phase | Phase 1, Phase 2 |
| Condition | Multiple Sclerosis |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Triple |
| Enrollment | 44 |
| Arms in the primary outcome | 2 |
| Lead sponsor | National Institute of Neurological Disorders and Stroke (NINDS) |
| Results posted | Yes |
2. Clinical Question
Population
People with secondary-progressive multiple sclerosis were the intended population. The registry description specifies an age range of 18 to 65 years and at least 3 months off immunosuppressive therapy. The trial title further describes low-inflammatory secondary-progressive multiple sclerosis.
Intervention
Rituximab was administered by both intravenous and intrathecal routes. The active-treatment description specifies rituximab into cerebrospinal fluid (CSF) and intravenously at Month 0, another intravenous administration at Month 0.5, and further CSF administrations at months 1.5 and 12.
Comparator
The placebo group received normal saline into the CSF and intravenously, following the same administration schedule described for the active group.
Primary question
The registry describes an interim assessment of whether active treatment changed CSF CXCL13 by 3 months after the first drug administration. The stated trial-continuation threshold was at least a 25% decrease in CSF CXCL13 induced by active treatment, with significance level p=0.025.
The clinical question concerns a biological measurement in CSF, rather than a direct comparison of disability or everyday function as the primary outcome. The registry describes CXCL13 as a chemokine released by activated B cells, T cells, and follicular dendritic cells, and notes its previous link with MS inflammation in the brain and spinal cord. The outcome description says pretreatment measurements were taken at month -12 and month 0 and averaged, then compared with the measurement at month 3.
The trial also listed clinical and biological secondary outcomes, including CSF B cell numbers, disability measures, walking, hand function, and a composite functional measure. Those outcomes broaden the questions considered by the study, but the posted primary result addressed the early CSF CXCL13 assessment. The registry record does not report whether the continuation threshold was met as a formal decision, or how that decision related to the trial's terminated status.
3. Trial Design
RIVITaLISe was registered as a randomized, parallel-group, triple-masked Phase 1 and Phase 2 trial. Its recorded enrollment was 44. The registry lists multiple sclerosis as the condition and the National Institute of Neurological Disorders and Stroke (NINDS) as sponsor. The record gives a start date of 2010-09, a primary completion date of 2015-12, and a status of terminated. The reason for termination is not reported in the registry record.
The active treatment combined rituximab delivered intravenously and intrathecally, meaning into the CSF through lumbar puncture. The placebo group received normal saline by both routes. The treatment descriptions specify administrations at Month 0, Month 0.5, months 1.5, and 12. The registry also describes a 1-year pretreatment baseline period followed by a 2-year treatment period. Participants were to provide blood samples during treatment; additional studies could be performed if participants consented.
The registry lists a baseline group as well as the placebo and rituximab groups in some results. Baseline is described as participants in their first year before the study-drug phase. It should not be treated as another randomized treatment arm based on the information in the registry record.
The posted primary outcome reports results for 9.0 participants in the placebo group and 14.0 in the rituximab group. The primary outcome description says the continuation decision analyzed change from baseline to 3 months after treatment in patients who received active drug; the posted results nevertheless include a placebo value. The reasons for the different group sizes and the relationship between this description and the displayed groups are not reported in the registry record. Further detail on the randomization procedure, allocation concealment, masking roles, and any changes to the planned design is not reported 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: One subject received an open label study drug under a compassionate use amendment of the protocol. This subject is not reflected in the data analysis for the primary or secondary outcome measures.
Year 1: Baseline Monitoring
| Stage | Baseline | Placebo | Rituximab |
|---|---|---|---|
| STARTED | 43 | 0 | 0 |
| COMPLETED | 27 | 0 | 0 |
| NOT COMPLETED | 16 | 0 | 0 |
Reasons for not completing this period:
| Reason | Baseline | Placebo | Rituximab |
|---|---|---|---|
| Study terminated | 7 | 0 | 0 |
| Withdrawal by Subject | 7 | 0 | 0 |
| Started on DMT | 2 | 0 | 0 |
Years 2 & 3: Treatment Randomization
| Stage | Baseline | Placebo | Rituximab |
|---|---|---|---|
| STARTED | 0 | 9 | 18 |
| COMPLETED | 0 | 5 | 7 |
| NOT COMPLETED | 0 | 4 | 11 |
Reasons for not completing this period:
| Reason | Baseline | Placebo | Rituximab |
|---|---|---|---|
| Study terminated | 0 | 4 | 7 |
| Withdrawal by Subject | 0 | 0 | 3 |
| Adverse Event | 0 | 0 | 1 |
Analysis population for the primary outcome, as defined in the registry: For the decision to continue trial, only change from baseline to 3 months post-treatment was analyzed in patients who received active drug
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 | Placebo | Rituximab | Baseline | Total |
|---|---|---|---|---|---|
| Participants analysed | 9 | 18 | 16 | 43 | |
| Age, Categorical: <=18 years | Participants | 0 | 0 | 0 | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 9 | 18 | 16 | 43 |
| Age, Categorical: >=65 years | Participants | 0 | 0 | 0 | 0 |
| Sex: Female, Male: Female | Participants | 2 | 9 | 11 | 22 |
| Sex: Female, Male: Male | Participants | 7 | 9 | 5 | 21 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 | 0 | 0 | 0 |
| Race (NIH/OMB): Asian | Participants | 0 | 0 | 0 | 0 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 | 0 | 0 | 0 |
| Race (NIH/OMB): Black or African American | Participants | 3 | 0 | 1 | 4 |
| Race (NIH/OMB): White | Participants | 6 | 18 | 13 | 37 |
| Race (NIH/OMB): More than one race | Participants | 0 | 0 | 1 | 1 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 0 | 0 | 1 | 1 |
6. Primary Endpoint
The registry lists the primary outcome as Analysis of Changes in CSF CXCL13 Induced by Active Treatment (Rituximab) Measured 3 Months After 1st Drug Administration, measured over 3 months.
| Element | Registry entry |
|---|---|
| Result type | Median |
| Measure of spread | Inter-Quartile Range |
| Unit | percentage of b cell depletion |
| Endpoint classification | not reduced to a single comparison |
The primary outcome is described as the analysis of changes in CSF CXCL13 induced by active treatment, measured 3 months after the first drug administration. The registry says that two pretreatment CSF measurements, collected at month -12 and month 0, were averaged and compared with the month 3 measurement. This makes the endpoint an early change from a pretreatment reference, rather than a measurement of long-term clinical progression.
The registry identifies CXCL13 as a chemokine released by activated B cells, T cells, and follicular dendritic cells, and describes its prior association with MS inflammation in the brain and spinal cord. A CSF measurement was used to assess a biological response in the fluid surrounding the brain and spinal cord. The registry's continuation criterion was at least a 25% decrease in CSF CXCL13 with significance level p=0.025.
There is a labeling inconsistency in the record: the primary outcome title and description concern CXCL13, while its unit is listed as “percentage of b cell depletion.” The result is reported as a median, with inter-quartile range specified as the dispersion measure, but no inter-quartile range values are posted. The registry does not report further details that resolve this difference in labeling or explain the intended interpretation of the unit.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The posted primary result gives a median value of 0 for placebo and -11.9 for rituximab. The registry lists the outcome unit as percentage of b cell depletion, although the outcome title and description refer to change in CSF CXCL13. The rituximab result is therefore best read with that labeling inconsistency in mind. The reported bounds are 0 to 0 for placebo and -100.0 to 0 for rituximab; the record does not identify what those bounds represent. Although inter-quartile range is named as the dispersion measure, corresponding spread values are not posted.
The protocol-stipulated continuation threshold was at least a 25% decrease in CSF CXCL13 following active treatment, with significance level p=0.025. The posted median for rituximab is -11.9, which is smaller in magnitude than that stated decrease threshold. However, the record does not provide an analysis p-value or a formal decision about whether the criterion was met. A median alone does not show the full distribution of individual results, and the inconsistent unit makes it especially important not to treat the displayed value as a fully clarified estimate of the CXCL13 change.
The registry labels the primary assessment an interim analysis and describes it as an assessment for the decision to continue the trial. The trial status is terminated, but the reason for termination and whether this particular endpoint determined that status are not reported in the registry record. The posted result cannot establish the reason the study stopped.
The primary outcome is a biological measure at 3 months. It does not itself show whether disability, walking, hand function, or other clinical outcomes changed. The registry lists such measures among secondary outcomes, but the record summarized for this analysis does not provide numerical results for them. It also does not provide a comparative effect estimate with a confidence interval or a p-value for the primary result. Consequently, the precision and statistical evidence for a between-group difference cannot be judged from the posted primary summary alone.
The groups also have different posted primary-result sample sizes: 9.0 for placebo and 14.0 for rituximab. The outcome description's decision population refers to patients who received active drug, while results are displayed for both groups. The registry does not explain these details or report how missing observations were handled. They limit interpretation of how representative the summaries are of all randomized participants.
These results describe what the registry reports, not a conclusion about treatment benefit or lack of benefit. They indicate a median of -11.9 in the rituximab group under the posted outcome labeling, alongside a stated continuation criterion and incomplete information about the analysis. The data in this record are not sufficient to reconstruct the trial's decision process or to assess the clinical meaning of the endpoint by themselves.
9. Statistical Methods Explained
What does a median report?
The primary outcome uses a median. In general, the median is the middle of an ordered set of observations, so it describes a central value without requiring extreme observations to have the same influence they would have on an arithmetic mean. A median is useful when the distribution may be skewed or when a few values are unusually high or low. It does not describe how tightly observations cluster, nor does it show how many participants had a particular response.
The registry names the inter-quartile range as the dispersion measure. In general, an inter-quartile range describes the spread of the middle half of a distribution. Here, the record does not post the inter-quartile range values, despite naming that measure. The bounds shown with the arm summaries are -100.0 to 0 for rituximab and 0 to 0 for placebo, but the record does not state whether these are observed ranges, confidence limits, or another kind of bound. They should not be interpreted as confidence intervals without clarification.
How should a treatment contrast be assessed?
In general, a randomized comparison is most informative when it estimates the difference between groups, with uncertainty around that estimate. A group-specific median is not itself a between-group treatment effect, and subtracting the two medians would not necessarily estimate the difference in group medians or an adjusted treatment effect. The registry summary does not report a formal comparative estimate, its uncertainty, or a primary-outcome p-value. It therefore does not permit a complete assessment of the size or precision of a treatment contrast.
The protocol description sets a continuation threshold of at least a 25% decrease in CSF CXCL13 induced by active treatment and significance level p=0.025. This is a decision rule described in the record, not a result. In general, a prespecified threshold helps define what evidence would be considered sufficient for a particular trial decision. The record does not report the analysis p-value or state whether the threshold was met. Moreover, the result's unit refers to percentage of B cell depletion while the endpoint narrative concerns CXCL13; this complicates direct comparison of the posted median with the stated CXCL13 criterion.
Why does the analysis population matter?
The primary outcome description says that, for the decision to continue the trial, change from baseline to 3 months post-treatment was analyzed in patients who received active drug. That wording identifies a population for the continuation assessment, but does not fully define it. The posted primary results include a placebo group as well as an active-treatment group. The registry does not explain the relationship between the stated decision population and the reported group summaries, or describe whether an intention-to-treat population, a per-protocol population, or another analysis population was used for other analyses.
In general, analysis populations answer different questions. Including everyone as randomized can preserve the benefits of randomization, while restricting analysis to people who received treatment may describe outcomes among those treated but can introduce differences related to treatment receipt. This is general statistical context; the registry record does not say which approach was used beyond its description of the continuation assessment. The reasons for the posted group sizes and the number of participants with missing endpoint measurements are also not reported.
What does masking contribute?
The design is described as triple-masked. In general, masking can reduce the influence of expectations on treatment delivery, participant reports, or outcome assessment, depending on who is masked. The registry record does not identify which roles were masked or describe how masking was maintained, so the specific protections cannot be evaluated. Randomized allocation and masking are design features; neither replaces transparent reporting of outcome definitions, analysis methods, estimates, and uncertainty.
How should a continuation threshold be read?
The endpoint is characterized as an interim analysis, and the record states a significance level of p=0.025 for the continuation criterion. In general, interim assessments can support decisions before all planned follow-up is complete, but the statistical interpretation depends on the planned analysis and how repeated looks at data were handled. The record does not report the number or timing of interim analyses, any adjustment for repeated testing, or a full statistical analysis plan. It is not possible to infer those details from the stated threshold alone.
The trial is recorded as terminated, but that status is not itself a statistical result. The registry does not report whether termination followed the primary endpoint assessment, a safety concern, recruitment difficulty, a funding decision, or another reason. No cause should be inferred from the status or from the posted median.
What can sample-size planning illustrations establish?
In general, a sample-size calculation describes the number of participants that might be needed under specified assumptions to detect an effect with a chosen statistical procedure. A planning illustration based on an observed effect is not observed power, and it does not show that the completed trial had adequate power. Its output depends on assumptions about the target effect, variability, allocation, significance level, and analysis method. The registry record does not report the trial's original sample-size justification or enough information to independently evaluate its design assumptions. Any planning illustration should therefore be understood as hypothetical rather than as evidence about the precision of the completed trial.
For this endpoint, the record specifies a median and inter-quartile range, but does not provide the inter-quartile range values or a comparative analysis. In general, planning based on a median-based outcome may require assumptions suited to the outcome's distribution and chosen test; a simple normal approximation may not reflect every feature of such an analysis. No inference about the original design can be drawn from a planning scenario alone.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists 13 outcome measures and 11 posted secondary outcomes. It also lists several related measures, including repeated entries for EDSS and Scripps Neurological Rating Scale. A set of outcomes creates the general possibility of multiple statistical tests, in which the chance of at least one apparently unusual finding can increase when many tests are conducted. The registry record does not report whether or how multiplicity was addressed, or identify a hierarchy among secondary outcomes.
The primary endpoint description gives a continuation criterion with significance level p=0.025. That is useful information about the stated decision threshold, but it does not by itself describe a multiplicity strategy or explain how the threshold relates to other analyses. The number and timing of interim analyses, any adjustment for repeated looks, and the broader statistical analysis plan are not reported in the registry record.
The record gives a specific primary-outcome analysis population description for the continuation decision: patients who received active drug, with change from baseline to 3 months considered. It also posts placebo and rituximab summaries. The record does not clarify which population underlies each posted summary or report a broader primary analysis population definition.
Missing-data counts, reasons for missing measurements, and methods for handling missing data are not reported in the registry record. The record does not state whether analyses used imputation, complete cases, or another approach. These omissions matter because missing outcomes can affect both the estimate and its precision, especially if missingness differs between groups or is related to participants' outcomes. The available summaries do not establish whether that occurred.
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 |
|---|---|---|---|
| Placebo | 4 | 9 | 44.4% |
| Rituximab | 4 | 18 | 22.2% |
| Baseline | 0 | 43 | 0.0% |
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 |
|---|---|
| Placebo | 9 of 9 |
| Rituximab | 18 of 18 |
| Baseline | 8 of 43 |
Most frequent serious adverse event terms
| Event term | Organ system | Placebo | Rituximab | Baseline |
|---|---|---|---|---|
| Post LP Headache | Injury, poisoning and procedural complications | 1 of 9 | 1 of 18 | 0 of 43 |
| Mass | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | 1 of 9 | 1 of 18 | 0 of 43 |
| Elevated Blood Sugar | Endocrine disorders | 1 of 9 | 0 of 18 | 0 of 43 |
| urinary tract infection | Renal and urinary disorders | 0 of 9 | 1 of 18 | 0 of 43 |
| Neck and Back Pain | Musculoskeletal and connective tissue disorders | 1 of 9 | 0 of 18 | 0 of 43 |
| Cognitive Decline | Nervous system disorders | 1 of 9 | 0 of 18 | 0 of 43 |
| Paresthesia | Nervous system disorders | 0 of 9 | 1 of 18 | 0 of 43 |
| Gallstones | Hepatobiliary disorders | 1 of 9 | 0 of 18 | 0 of 43 |
| Cellulitis | Skin and subcutaneous tissue disorders | 0 of 9 | 1 of 18 | 0 of 43 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Placebo | Rituximab | Baseline |
|---|---|---|---|---|
| UTI | Renal and urinary disorders | 5 of 9 | 5 of 18 | 0 of 43 |
| Paresthesia | Nervous system disorders | 0 of 9 | 7 of 18 | 0 of 43 |
| Tachycardia | Cardiac disorders | 2 of 9 | 4 of 18 | 0 of 43 |
| headache | Nervous system disorders | 0 of 9 | 5 of 18 | 0 of 43 |
| rash | Skin and subcutaneous tissue disorders | 0 of 9 | 4 of 18 | 0 of 43 |
| anemia | Blood and lymphatic system disorders | 2 of 9 | 1 of 18 | 0 of 43 |
| Nausea/Vomitting | Gastrointestinal disorders | 1 of 9 | 1 of 18 | 0 of 43 |
| Enhancing brain lesion | Nervous system disorders | 0 of 9 | 0 of 18 | 2 of 43 |
| Upper Respiratory Infection | Respiratory, thoracic and mediastinal disorders | 1 of 9 | 1 of 18 | 0 of 43 |
| Fall | Musculoskeletal and connective tissue disorders | 0 of 9 | 2 of 18 | 0 of 43 |
Serious events with the highest arm-level rate: elevated blood sugar (11.1%), post lp headache (11.1%), neck and back pain (11.1%), cognitive decline (11.1%), mass (11.1%).
The registry reports serious adverse events for the placebo and rituximab groups, as well as a baseline group. In the placebo group, 4 participants were recorded as affected among 9 at risk; in the rituximab group, 4 were affected among 18 at risk. For the baseline group, no serious adverse events were recorded among 43 at risk. These are the registry's group-specific figures; the record does not explain why the at-risk counts differ across groups or how the baseline period relates to treatment-period safety.
For other, non-serious adverse events, the registry records 9 affected among 9 at risk in placebo, 18 among 18 in rituximab, and 8 among 43 in the baseline group. These figures indicate whether participants were recorded as affected, not the total number of individual events or their duration. They do not establish that all events were equally severe or related to treatment.
The serious-event terms listed include elevated blood sugar, post LP headache, neck and back pain, cognitive decline, mass, and gallstones, each shown as 11.1%. The denominator and counting method for these term percentages are not reported in the registry record. Death counts are not reported in the registry record. The figures should be read as descriptive registry reporting, not as a comparative safety analysis establishing causation or differences in risk.
12. What the Result Does, and Does Not, Mean
The registry result is a descriptive summary of a primary biological endpoint: the median posted value is 0 for placebo and -11.9 for rituximab at the stated 3-month assessment. The endpoint narrative concerns change in CSF CXCL13, while the unit is recorded as percentage of b cell depletion. That mismatch, the absence of inter-quartile range values, and the lack of a stated meaning for the displayed bounds make the numerical result difficult to interpret precisely.
The record states a continuation criterion of at least a 25% decrease in CSF CXCL13 and significance level p=0.025. It does not report a primary p-value or whether the criterion was formally met. Nor does it explain whether the study's terminated status was related to this assessment. The posted results therefore do not establish the trial's decision process.
The trial also listed clinical secondary outcomes, including disability ratings, walking, hand function, and a functional composite, but numerical findings for these are not included in the record. The primary result cannot be used as a substitute for those clinical outcomes. It describes an early biological measurement, not a direct measurement of long-term disability or function.
In general, treatment effects are most clearly assessed through a prespecified comparison between groups accompanied by an estimate of uncertainty and transparent analysis details. Those elements are not reported for the primary outcome in this record. The summaries also have different posted group sizes, and the registry does not describe missing-data handling or fully clarify the analysis populations. These limits prevent a robust assessment of comparative magnitude and precision from the posted figures alone.
Accordingly, the result should be read narrowly: it records a median value in each group for an endpoint whose labeling needs clarification. It does not, on its own, show whether rituximab changed clinically meaningful outcomes, whether a treatment effect was statistically established, or why the trial ended.
13. Why This Trial Matters Statistically
This trial is statistically notable because its primary endpoint was an early biological measure linked in the registry narrative to MS inflammation, while the listed secondary outcomes included clinical measures of disability and function. That distinction matters: a change in a laboratory marker and a change in how participants function are different types of evidence and answer different questions.
The record also illustrates why precise outcome definitions are essential. The primary title and description refer to CSF CXCL13, but the unit is labeled percentage of B cell depletion. When the outcome's biological target and reported unit do not align clearly, readers cannot confidently map a numerical summary to the stated continuation criterion. The absence of the inter-quartile range and of a reported comparative estimate further limits understanding of variability and precision.
The stated continuation threshold and significance level provide some information about the intended decision framework. Yet an interim endpoint cannot be fully interpreted without knowing how repeated analyses were handled, what population was analyzed, and whether the stated criterion was met. Those details are not reported in the registry record. The terminated status adds context about the study's course, but without a reported reason it cannot explain the statistical outcome.
The safety summaries also demonstrate the importance of clear denominators and analysis periods. The registry presents at-risk and affected counts for treatment groups and a baseline group, but does not explain the differing denominators or the basis for the listed event-term percentages. Descriptive counts are informative as registry entries, but they are not by themselves a controlled comparison of treatment-related risk.
Overall, the record shows how randomized design features and posted outcome values can coexist with important gaps in interpretation. Clear reporting of endpoint units, analysis populations, missing data, uncertainty, and decision rules is necessary to connect statistical results with the question a trial set out to answer.
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.
Several trial-specific reporting limitations constrain interpretation. The most immediate is the mismatch between the primary outcome's CXCL13 title and description and its unit, “percentage of b cell depletion.” The record does not clarify whether the unit is mislabeled or how the reported median should be mapped to the stated continuation criterion. The endpoint description identifies inter-quartile range as the dispersion measure, but no inter-quartile range values are posted. The displayed bounds are not defined, so they cannot safely be treated as confidence limits or observed ranges.
The primary result includes different posted group sizes, and the record does not explain why. Its description says the continuation decision used active-drug recipients, while the posted results include both placebo and rituximab. The analysis population for each summary, the number with missing endpoint data, and methods for handling missingness are not reported. The registry also does not report a comparative effect estimate, confidence interval, or p-value for the primary endpoint.
The record does not give a full statistical analysis plan, a sample-size justification, or details on any multiplicity adjustment or repeated interim analyses. Although a significance level is stated for the continuation criterion, the number and timing of assessments and the resulting decision are not reported. The reason the trial was terminated is also not reported in the registry record.
Finally, safety figures include different at-risk counts across treatment and baseline groups, without an explanation of their relationship or the relevant observation periods. The denominator for the listed serious-event term percentages is not reported. These limitations are specific reporting gaps; they do not establish that a particular bias or problem occurred.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Double Blind Combination of Rituximab by Intravenous and Intrathecal Injection Versus Placebo in Patients With Low-Inflammatory Secondary Progressive Multiple Sclerosis (RIVITaLISe) — NCT01212094.
- Registry record last updated 2016-03-28; status last verified 2016-03.
- Results first posted 2016-03-28.
- 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
RIVITaLISe was a randomized, parallel-group, triple-masked Phase 1 and Phase 2 trial of intravenous and intrathecal rituximab versus normal saline in secondary-progressive multiple sclerosis. Recorded enrollment was 44, and the trial status is terminated. The registry describes a 1-year pretreatment baseline period followed by a 2-year treatment period.
The primary outcome was an interim assessment of CSF CXCL13 change 3 months after the first administration. The posted median was 0 for placebo and -11.9 for rituximab. The outcome description and recorded unit do not align clearly, and the record does not report the primary analysis p-value, a comparative uncertainty estimate, or whether the continuation criterion was met. The record also lists clinical secondary outcomes and adverse-event summaries, but does not provide a reason for termination or several analysis details needed to interpret the results fully.