Abstract 9991: Can Isosorbide Dinitrate Save Lives of Hospitalized COVID Patients with Hypertension and a Defined Cardiac Injury?
Bibliographic record
Abstract
Introduction: As defined by MB-CPK, hsTn-I, MB, or EKG and/or cardiac echo abnormalities, cardiac injury (CI) determines a median survival time (MST) of 10 days for hospitalized COVID patients (HCPs). HCPs without defined CI have an MST beyond 39 days (Huang, et al ., see Figure). Hypertension (HTN) presents in 17-41% of HCPs in various studies, with COVID mortality independent of HTN. Therefore, a randomized clinical trial (RCT) is proposed for HCPs with CI and incidental BP elevation to compare IV isosorbide dinitrate (ISDN) with usual anti-HTN care (UC). Vasodilatory ISDN lowers BP, and has been proposed an an anti-SARS-CoV-2 drug. Others report improved survival of ISDN treated Coxsackie B3 virus-infected mice as evidence for anti-viral activity. The endpoint for this CI RCT pilot of 100 ISDN-treat HCPs and 100 UC controls is mortality. Secondary endpoints are interval biomarkers to dissect ISDN anti-viral action. Methods: Log-rank analysis was performed with 1:1 allocation. Accrual time was 180 days with a 60-day follow-up. Power was 0.8 with a type I error of 0.05. Results: For 200 total subjects, an MST greater than 14.9 days in the ISDN arm was significant if UC stays at 10 days (see Figure). Conclusions: Testing repurposed ISDN as a COVID drug is feasible. A successful pilot with improved MST suggests ISDN has anti-SARS-CoV-2 action, since COVID mortality is independent of HTN. Biomarkers could include viral clearance, oxygenation, D-dimer, IL-6, LDH, as well as platelet and lymphocyte counts. The need to treat HCPs with elevated BP per guidelines permits study entry. Cross-over treatment occurs if a regimen fails. Immunomodulators and remdesivir are administered per COVID treatment guidelines for all HCPs. IV ISDN, bolused and/or infused, avoids 1 st pass hepatic effects. IV IDSN is approved in most countries, but not in the USA or Canada. A successful pilot would permit larger IV ISDN RCTs as IND RCTs, and can serve as a template for other treatments for HCPs with defined CI.
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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 | 0.006 | 0.007 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.002 | 0.002 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.002 | 0.001 |
| Insufficient payload (model declined to judge) | 0.012 | 0.001 |
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".