Sepsis damages the blood vessel lining and its protective "glycocalyx," contributing to organ failure and death. This pilot, randomized, blinded study will test whether giving fresh frozen plasma (FFP)-either as intermittent boluses or as a continuous infusion-protects or repairs the glycocalyx compared with look-alike placebo fluid (lactated Ringer's with multivitamins), and whether this leads to better clinical outcomes. We will measure blood and urine biomarkers of glycocalyx injury and track organ support needs, ICU/hospital-free days, and survival through 28-90 days.

Multicenter, blinded, placebo-controlled randomized pilot trial comparing: (1) Fresh Frozen Plasma bolus regimen; (2) FFP continuous infusion; and (3) placebo (Lactated Ringers with multivitamins, administered as bolus or semi-continuous to maintain blinding). Primary biologic readout is change in syndecan-1 (glycocalyx degradation) with additional endothelial activation and inflammation markers; key clinical endpoints include mortality and organ failure-free days. Target enrollment is 45 adults with sepsis (Sequential Organ Failure Assessment (SOFA) ≥2) within Intensive Care Unit or Emergency Department settings.

Inclusion Criteria:

• Age ≥18 years
• Confirmed or suspected infection (pathogen detected or antimicrobial administered)
• SOFA score ≥2
• ICU patient or ED patient with anticipated ICU admission

Exclusion Criteria:

• Unable to randomize within 24h of meeting inclusion criteria
• Current hospitalization >2 days
• Decision to withhold life-sustaining treatment (exception for DNR only)
• Moribund; not expected to survive 24h
• Life expectancy <28 days from non-sepsis condition
• Any condition where participation isn't in the patient's best interest or limits assessments
• Prisoner
• Pregnancy
• Concurrent interventional trial with overlapping treatments/outcomes
• Inability to obtain patient/LAR consent
• History of Transfusion Related Acute Lung Injury (TRALI) or Transfusion Associated Circulatory Overload (TACO)
• End Stage Renal Disease
• Chronic tracheostomy with ventilator use

Plan Description:

De-identified individual participant data (IPD) collected during the study will be made available. This will include the analyzable dataset underlying the primary and secondary outcomes, along with relevant clinical variables, laboratory data, and derived variables necessary to reproduce the reported findings. Data will be de-identified in accordance with applicable regulatory standards prior to sharing.

Time Frame:

Data will be available beginning 12 months after publication of the primary results and will remain available for at least 5 years thereafter.

Access Criteria:

Data will be made available to qualified investigators for secondary analyses upon reasonable request. Requests must include a brief proposal outlining the intended use of the data and will require execution of a data use agreement (DUA) to ensure appropriate use and protection of participant confidentiality. Data will be shared via a secure institutional or third-party data repository. Access is