Sepsis
Conditions
Keywords
Sepsis, Fresh Frozen Plasma, Endothelium, glycocalyx
Brief summary
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.
Detailed description
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.
Interventions
BIOLOGICALFresh Frozen Plasma (blood product)
Fresh Frozen Plasma
DRUGMVI and lactated ringers
placebo
Sponsors
Beth Israel Deaconess Medical Center
University of Colorado Health
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Median Syndecan-1 Concentration | baseline to study days 1,3,5 | Change in Median Syndecan-1 Concentration |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| All-cause mortality to Day 28 | 28 days | All-cause mortality to Day 28 |
| Organ failure-free days | 28 days | Organ failure-free days to Day 28 (alive and without assisted ventilation, new RRT, or vasopressors). |
| Sequential Organ Failure Assessment (SOFA) Score | change over days 1, 3, 5 | Sequential Organ Failure Assessment (SOFA) Score is an established score for quantifying organ dysfunction in sepsis with a range of 0-24 points, with higher numbers indicating greater organ dysfunction and higher severity. |
Contacts
CONTACTNathan I. Shapiro, MD, MPH
Outcome results
None listed