The incidence of serious bleeding events in a global, single-arm, open-label trial of Drotrecogin alfa (activated) in adult patients with severe sepsis (ENHANCE): comparisons with PROWESS
Bibliographic record
Abstract
A global, single-arm, open-label trial of Drotrecogin alfa (activated) (DrotAA) in adult patients with severe sepsis was subsequently conducted at 361 sites in 25 countries (ENHANCE, n = 2378). Reported here are 28-day all-cause mortality and safety data. Inclusion/exclusion criteria and the definition of serious adverse events (SAE) were similar to PROWESS. Patients at high risk of bleding were excluded from participation. SAE bleeding rates, including intracranial hemorrhage (ICH), during the study drug infusion period (infusion period + 1 day) were determined and the all-cause mortality was assessed at day 28. Serious bleeding rates and fatal event rates for PROWESS and ENHANCE are presented in Table 1 . Overall 28-day mortality: PROWESS placebo = 30.8%, PROWESS DrotAA = 24.7%, ENHANCE DrotAA = 25.3%. As in PROWESS, bleeding was the most common drug-related complication associated with DrotAA. A total 48.9% of SAE bleeding events were adjudicated as procedure-related. In ENHANCE, the ICH rate during infusion was 0.6% ( n = 15), of which five (0.2%) were fatal. ICH rates for placebo vs DrotAA in PROWESS were 0% and 0.2% ( n = 2, both fatal), respectively. A higher postinfusion rate of serious bleeding was observed in ENHANCE, suggesting a higher overall background bleeding rate, relative to PROWESS. Twenty-eight-day survival was similar in PROWESS and ENHANCE. Serious bleeding events during infusion of DrotAA were slightly more frequent in ENHANCE than in PROWESS; the proportion of fatal bleeding events was the same. However, the background bleeding rate in ENHANCE may have been higher. The ENHANCE safety and efficacy data are highly consistent with PROWESS, and reinforce the favorable benefit–risk profile of DrotAA in patients with severe sepsis.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.005 | 0.003 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.002 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.000 | 0.001 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".