The Membrane-Activated Chelator Stroke Intervention (MACSI) Trial of DP-b99 in Acute Ischemic Stroke: A Randomized, Double-Blind, Placebo-Controlled, Multinational Pivotal Phase III Study
Bibliographic record
Abstract
RATIONALE: Zinc is both a direct neurotoxin and a signaling mediator in multiple early and late detrimental processes following ischemia. DP-b99, a lipophilic moderate-affinity chelator of zinc, is a first-in-class multitargeted neuroprotective agent for ischemic stroke. DP-b99 has completed several Phase I studies and two double-blind placebo-controlled Phase II trials, which supported the safety of DP-b99 and were consistent with a beneficial effect on poststroke recuperation. AIM: Membrane-Activated Chelator Stroke Intervention is a Phase III study. The primary objective is to evaluate the safety and therapeutic effects of intravenous 1.0 mg/kg/day DP-b99, initiated within nine-hours of stroke onset in patients with moderately severe hemispheric acute ischemic stroke, through the analysis across the whole distribution of scores of the primary efficacy endpoint of the modified Rankin Scale, 90 days after the stroke. METHODS: The Membrane-Activated Chelator Stroke Intervention study is a randomized, double-blind, placebo-controlled, multicenter, multinational, parallel-arm trial comparing a placebo group to a group treated with intravenous DP-b99 for four consecutive days. Non-rtPA-treated acute ischemic stroke patients--with a baseline NIHSS score of 10-16 and a clinical syndrome that includes language dysfunction, visual field defect and/or neglect--will be stratified on a 1:1 basis to one of the two treatments. Half will be randomized within 0-4.5 h of stroke onset. Follow-up after the four treatment days will occur on days 12, 30 and 90. An interim futility analysis will be performed after primary endpoint data have been collected for 50% of 770 subjects planned to be enrolled. A data and safety monitoring board will assess safety data and will oversee the interim analysis. CONCLUSION: This Phase III Membrane-Activated Chelator Stroke Intervention trial is based on promising data derived from previous Phase I and II DP-b99 trials and capitalizes on lessons learned from failures of past stroke studies in relation to neuroprotection, patient selection and data analysis.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.004 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.002 | 0.001 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.000 | 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 teacher head, 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".