Tier 4 — mechanistic

Senolytics To slOw Progression of Sepsis (STOP-Sepsis) in elderly patients: Study protocol for a multicenter, randomized, adaptive allocation clinical trial

Milena Silva, David A. Wacker, Brian E. Driver, Abbey Staugaitis, Laura J. Niedernhofer, Elizabeth L. Schmidt, James L. Kirkland, Tamara Tchkonia, Tamara Evans, Carlos Hines Serrano, Steffen Ventz, Joseph S. Koopmeiners, Michael A. Puskarich, STOP-Sepsis Investigators
Trials 2024 25:698

Bibliography

PubMed
PMID 39434114
PubMed Central
PMC11492760
DOI
10.1186/s13063-024-08474-2
Trial registry
View on ClinicalTrials.gov Registered trial — results not yet published in a peer-reviewed journal.
Funding
National Institute on Aging, NIH, awards U01AG076929 and R33AG61456 through the Translational Geroscience Network.
Competing interests
The protocol reports that James L. Kirkland, Tamara Tchkonia and Mayo Clinic hold patents related to senolytic agents; Tamara Tchkonia holds shares in Unity Biotechnology. Other listed disclosures are described in the full paper.

Study snapshot

DesignMulticenter, randomized, double-blind, placebo-controlled, parallel-group Phase 2 trial using response-adaptive allocation.
ModelHospitalized adults aged 65 years or older with acute infection and sepsis-level organ dysfunction.
SamplePlanned n=220.
InterventionThree arms: fisetin 20 mg/kg as a single oral dose; fisetin 20 mg/kg once daily for two doses 24 hours apart; or placebo. The protocol therefore directly compares one-day versus two-day high-dose fisetin exposure.
DurationAcute 1- or 2-day dosing with outcomes through day 7, day 28 and day 90. Current registry status in September 2026: recruiting; estimated primary completion March 2027 and study completion June 2027.
EndpointsPrimary: change in composite cardiovascular, respiratory and renal SOFA score at day 7; Senescent CD3+ immune-cell abundance and senescence markers; Systemic inflammatory cytokines; Organ failure-free days; ICU days; 28-day mortality; Safety and serious adverse events

What the study showed, in plain terms

STOP-Sepsis is especially important for interpreting fisetin pulse dosing because it does not assume that two consecutive high-dose days are automatically necessary. Adults aged 65 years or older with sepsis are randomized to one 20 mg/kg dose, two 20 mg/kg doses 24 hours apart, or placebo. The trial is designed to determine which acute exposure strategy is more promising while also measuring senescent immune cells, inflammation, organ failure and safety.

Key findings

This is a protocol, not a results paper. Its main dosing significance is that the investigators are directly testing one 20 mg/kg dose against two 20 mg/kg doses 24 hours apart. That makes STOP-Sepsis strong evidence that modern human fisetin research does not treat a fixed two-day monthly schedule as a universally established requirement.

What this study can and cannot tell us

No efficacy results are yet available. The population is acutely ill older adults with sepsis, so the regimen cannot be generalized to healthy-aging or consumer supplementation. Response-adaptive allocation may also change the relative numbers assigned to the two fisetin arms as the trial progresses.

Citation network

Articles citing this research paper

1 article

Biohack Blueprint analyses that reference this study in their evidence base.

Editorial review

Reviewed by the Biohack Blueprint research team

Last verified

Dr. Khaled Mahmoud, MBBChCritical Care Medicine, Longevity Science & Editorial Direction Dr. Amr Yasser, PhDCardiometabolic, Musculoskeletal, Gut & Bioavailability Dr. Abdulla Mostafa, PhDCellular Senescence, Neurological, Mitochondrial & Brain-Ageing Biology