This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record.
1. Trial at a Glance
ARISE was a phase 3 randomized controlled trial evaluating Early Goal Directed Therapy (EGDT) as a treatment strategy for severe sepsis.
| Feature | ARISE |
|---|---|
| Condition | Severe Sepsis |
| Phase | Phase 3 |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | None |
| Primary purpose | Treatment |
| Enrollment | 1600 |
| Study start | 2008-10 |
| Primary completion date | 2014-07 |
2. Clinical Question
The central clinical question was whether Early Goal Directed Therapy should be used as a treatment strategy for patients with severe sepsis compared with the alternative management approach used in the randomized comparator arm.
Population
Patients with severe sepsis.
Intervention
Early Goal Directed Therapy (EGDT).
Comparator
The randomized comparator treatment approach.
Primary question
Does EGDT affect death from all causes at 90 days?
3. Trial Design
1600 participants
Two parallel arms
90 days
All-cause death
Early Goal Directed Therapy
Participants received the intervention of Early Goal Directed Therapy.
Comparator
Participants were assigned to the parallel comparator group.
4. Endpoints
| Endpoint | Registry definition | Time frame |
|---|---|---|
| Primary outcome measure | Death from all causes | 90 days |
5. Planned Analysis
The registry identifies death from all causes at 90 days as the primary outcome measure. ClinicalTrials.gov does not report posted statistical analyses or outcome results for the primary endpoint.
A mortality endpoint measured over a defined follow-up period is typically analyzed using methods appropriate for binary or time-to-event outcomes. Common approaches include comparing mortality proportions between randomized groups, estimating relative measures of effect, and using survival methods when timing of death events is incorporated.
When follow-up times differ among participants, survival analysis methods can incorporate censoring and estimate the probability of survival over time.
6. Statistical Methodology
Randomization
Randomization is the foundation of the treatment comparison. By assigning participants to intervention groups rather than allowing treatment choice, randomized trials aim to balance measured and unmeasured factors between groups at baseline.
Intention-to-treat analysis
For a randomized treatment comparison, the intention-to-treat principle analyzes participants according to their randomized assignment. This preserves the comparability created by randomization.
Mortality analysis
All-cause mortality is a clinically direct endpoint because the event definition does not depend on investigator attribution of cause of death.
7. Statistical Methods Explained
Why is randomization important?
Randomization reduces systematic differences between treatment groups and supports causal interpretation of comparisons.
Why measure death from all causes?
All-cause mortality avoids uncertainty caused by assigning specific causes of death.
Why does the 90-day time frame matter?
A prespecified follow-up window defines when the primary outcome is evaluated.
Why use survival methods?
Survival methods account for both whether an event occurs and when it occurs.
What does randomization not guarantee?
Randomization improves balance on average but does not make groups numerically identical in every characteristic.
Why is the analysis population important?
The population included in analysis affects interpretation of treatment comparisons.
8. Limitations
- Registry reporting: ClinicalTrials.gov does not report posted statistical analyses or outcome estimates for the primary endpoint.
- Interpretation of mortality: A mortality endpoint summarizes outcomes for the randomized population but does not describe individual patient trajectories.
- Follow-up definition: The primary endpoint is limited to the prespecified 90-day time frame.
- Unreported analysis details: Statistical details such as model specifications, missing data handling, interim analysis procedures, and multiplicity adjustments are not reported in the registry record.
9. Why This Trial Matters Statistically
ARISE is an important example for understanding how large randomized clinical trials evaluate treatment strategies using clinically meaningful endpoints.
| Concept | How it appears in ARISE |
|---|---|
| Randomization | Randomized parallel-group phase 3 design |
| Clinical endpoint | Death from all causes at 90 days |
| Treatment comparison | Early Goal Directed Therapy versus comparator |
| Sample size | 1600 participants |
| Follow-up | 90-day primary outcome assessment |
10. Sources
- ClinicalTrials.gov: NCT00975793
- PubMed: Publication record
- PubMed: Publication record
- PubMed: Publication record
- PubMed: Publication record
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11. Record Summary
ARISE provides a framework for understanding randomized evaluation of treatment strategies in severe sepsis. The trial design includes random allocation, a phase 3 parallel comparison, and a prespecified 90-day all-cause mortality endpoint.