Infectious Disease · Clinical trials
Sepsis Clinical Trials
Approved therapies, the pivotal-trial endpoints they were judged on, the magnitude of benefit — and the drugs that failed their endpoints, and why.
Indication overview
About sepsis — and why its trials are hard
Sepsis is life-threatening organ dysfunction caused by a dysregulated host response to infection; septic shock is its most severe form, marked by profound circulatory and metabolic derangement. It is a leading cause of hospital death worldwide and a syndrome rather than a single disease, which has profoundly shaped its therapeutics. There is no approved sepsis-specific drug that treats the underlying dysregulated response. Management rests entirely on supportive care: prompt source control, early broad-spectrum antibiotics, intravenous fluids, vasopressors, and organ support, guided by frameworks such as the Surviving Sepsis Campaign. The field is notorious for a graveyard of failed targeted therapies. Drotrecogin alfa (Xigris), an activated protein C approved in 2001, was withdrawn in 2011 after the PROWESS-SHOCK trial showed no survival benefit. Numerous anti-inflammatory, anticoagulant, and immunomodulatory agents targeting endotoxin, cytokines, and Toll-like receptors have failed in large trials, reflecting sepsis heterogeneity. Current research emphasizes patient subphenotyping and precision-medicine enrichment to succeed where broad approaches failed.
Where trials have failed
Drugs that missed their endpoint — and what contributed
The most instructive lessons in sepsis development come from programmes that failed the endpoint that mattered.
| Drug / trial | Endpoint outcome | What contributed |
|---|---|---|
| Drotrecogin alfa (activated protein C) — PROWESS-SHOCK (confirmatory) | No mortality benefit in septic shock; drug voluntarily withdrawn worldwide in 2011 | Initial PROWESS approval (2001) not confirmed; bleeding risk without survival gain led to withdrawal |
| Eritoran (TLR4 antagonist) — ACCESS | Failed to reduce 28-day mortality in severe sepsis | Targeting endotoxin/TLR4 signaling did not improve survival across a heterogeneous population |
| Selepressin (selective vasopressin V1a agonist) — SEPSIS-ACT | Failed to improve ventilator- and vasopressor-free days in septic shock | Did not meet primary or key secondary endpoints; trial stopped for futility |
| High-dose vitamin C (with thiamine/hydrocortisone) — VITAMINS / CITRIS-ALI | No improvement in resolution of organ dysfunction or key clinical outcomes | Metabolic resuscitation hypothesis not confirmed in rigorous randomized trials |
| Anti-TNF agents (e.g., afelimomab) — Multiple anti-cytokine sepsis trials | Little to no consistent mortality benefit | Blocking single mediators failed given the redundant, heterogeneous host response |
Choosing the right endpoint
Primary endpoints that matter in sepsis trials
- 28-day (or 90-day) all-cause mortality — The definitive and most common primary endpoint in sepsis interventional trials
- Vasopressor-free days — Reflects reversal of shock; used as a shorter-term efficacy signal
- Ventilator-free days — Captures respiratory organ support burden and recovery
- Resolution of organ dysfunction (SOFA) — Change in Sequential Organ Failure Assessment score tracks organ recovery
How iNGENū runs sepsis trials
Physician-led design, built for FDA submission
Endpoint & biomarker strategy
Board-certified specialists design endpoints and patient selection aligned to current FDA guidance for this indication.
FDA-ready data
Built to ICH-GCP and 21 CFR 312.120, with direct FDA submission — data accepted by the FDA, EMA and MHRA.
Faster, lower-cost delivery
~4-week ethics via the TGA CTN scheme, up to 43.5% R&D rebate, and 80–90% below US CRO cost.
Request a fixed-milestone proposal and a tailored endpoint & feasibility summary for this indication.
Frequently asked questions
Sepsis clinical trials — FAQs
Is there a drug that treats sepsis itself?
What happened to Xigris (drotrecogin alfa)?
Why have so many sepsis drugs failed?
Ready to discuss your sepsis trial?
Talk to our physician-led team about an FDA-ready, cost-efficient trial design.
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