Condition
Sepsis
6 compounds were checked against sepsis, and every one of them earned a row.
Last updated
Compounds with a graded row
Ordered by rung, strongest first. The rung rates the study design; the chip beside it says what the study measured. Both are needed.
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Bactericidal/Permeability-Increasing Protein (BPI)
human RCT Direct outcome Not approved for this condition
- Who was studied
- children aged 2 weeks to 18 years with severe meningococcal sepsis, n=393 randomised, 22 centres in the UK and USA, outcomes to day 60; enrolment predates Sepsis-3 and used clinical meningococcaemia criteria, not a SIRS or Sepsis-3 definition
The molecule tested was rBPI21, a recombinant 21-kDa amino-terminal fragment of human BPI, not full-length BPI. This randomised placebo-controlled trial measured mortality, amputation and paediatric overall performance category, and it did not meet its primary endpoint: mortality was 7.4% with rBPI21 versus 9.9% with placebo (p=0.48), with the authors attributing the null result partly to placebo mortality far below the 25% assumed in the power calculation. No approval for sepsis exists in any jurisdiction, and the population was paediatric meningococcal sepsis only, not adult sepsis of any cause.
Source PubMed 2 primary sources read for this row
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Thymosin alpha-1
human RCT Direct outcome In registered trials
- Who was studied
- adults aged 18-85 with sepsis, n=1106 (552 thymosin alpha-1, 554 placebo), 22 centres in China, September 2016 to December 2020, 28-day follow-up; the enrolment definition is not established from the record read here
The TESTS trial was a multicentre, double-blind, placebo-controlled phase 3 trial measuring 28-day all-cause mortality, which occurred in 23.4% of the thymosin alpha-1 group and 24.1% of placebo (hazard ratio 0.99, 95% CI 0.77 to 1.27, p=0.93), with no secondary or safety outcome differing significantly. The earlier ETASS trial (six Chinese hospitals, severe sepsis, single-blind, no placebo) reported a mortality signal that the larger blinded trial did not reproduce, and meta-analyses lose the mortality benefit when restricted to multicentre or high-quality studies. No regulator has approved thymosin alpha-1 for sepsis.
Source PubMed 3 primary sources read for this row
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Adrenomedullin
animal in vivo Direct outcome Not approved for this condition
- Who was studied
- BALB/c and C57BL/6 mice, 6-8 weeks old, LPS endotoxaemia and caecal ligation and puncture models; adrenomedullin given intraperitoneally at 0.05-5.0 nmol per mouse (about 6-550 mcg/kg), survival followed 96 hours to 10 days
The only administration-and-mortality evidence on file is in mice: intraperitoneal adrenomedullin reduced lethality in LPS endotoxaemia and caecal ligation and puncture. The large human adrenomedullin literature in sepsis is not interventional - bio-ADM is measured as a prognostic marker of mortality and organ failure in septic patients, which is observational biology about a molecule the body already makes and is not evidence that giving adrenomedullin treats sepsis. The AdrenOSS-2 phase 2a trial (n=301, septic shock) tested adrecizumab, a non-neutralising anti-adrenomedullin antibody, which is a different intervention; it reported no difference in 90-day mortality, and in any case evidence about the antibody is not evidence about the peptide.
Source PubMed Central 3 primary sources read for this row
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Defensins
animal in vivo Direct outcome Not approved for this condition
- Who was studied
- C57BL/6 wild-type mice, caecal ligation and puncture sepsis; human neutrophil peptide 1 (HNP-1) given intraperitoneally at 0.5 or 10 mg/kg six hours after sepsis onset, mortality assessed to 48 hours and beyond
Administered human neutrophil peptide 1 worsened outcome: 80% of mice died at 10 mg/kg versus 20% at 0.5 mg/kg and 10% in controls, with more severe liver injury and disrupted liver interendothelial junctions. Defensins is a family, not one molecule - this result belongs to HNP-1 specifically, and the separate report of improved survival with rhesus theta-defensin RTD-1 concerns a different, non-human molecule. No human trial administering any defensin in sepsis is on file.
Source PubMed Central 2 primary sources read for this row
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LL-37 (Cathelicidin)
animal in vivo Direct outcome Not approved for this condition
- Who was studied
- male BALB/c mice, 7-10 weeks old, caecal ligation and puncture polymicrobial sepsis; LL-37 1 or 2 mcg per mouse intravenously immediately after surgery, survival followed 7 days
Synthetic human LL-37 was administered intravenously to septic mice and survival rose from 6.7% (untreated caecal ligation and puncture) to 36.4% at the 2 mcg dose; bacterial load and IL-1beta fell. This is a mouse mortality result at a microgram-per-mouse dose, and no human trial of administered LL-37 in sepsis is on file.
Source PubMed Central 1 primary source read for this row
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Urocortin
animal in vivo Direct outcome Not approved for this condition
- Who was studied
- BALB/c and C57BL/6 mice, 6-8 weeks old, LPS endotoxaemia and caecal ligation and puncture models; urocortin 1 given intraperitoneally at 0.05-5.0 nmol per mouse (about 6-550 mcg/kg), survival followed 96 hours (LPS) and 8-10 days (CLP)
Urocortin 1 was administered to mice after LPS challenge or caecal ligation and puncture and reduced lethality, alongside falls in TNF-alpha, IL-6, IL-1beta and nitric oxide. Mortality in rodents is the outcome measured; no human study administering urocortin in sepsis is on file, and no regulator has approved it for any condition.
Source PubMed Central 1 primary source read for this row
Every compound checked earned a row
Nothing was checked against sepsis and set aside. That is unusual — most conditions here have a list at the bottom of this page.
What this page does not say
It reports what was measured, in whom, and how directly. It does not say what to take or at what dose, and a row here is a record of a study rather than a reason to use anything. Every rung links to the rubric that assigned it.