Study of Protection And Repair of Endothelial-glycocalyx in Sepsis
- Conditions
- Sepsis
- Interventions
- Biological: Fresh Frozen Plasma (blood product)Drug: MVI and lactated ringers
- Registration Number
- NCT07160426
- Lead Sponsor
- Beth Israel Deaconess Medical Center
- 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) FFP bolus regimen; (2) FFP continuous infusion; and (3) placebo (LR with multivitamins, administered as bolus or 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 (SOFA ≥2) within ICU or ED settings.
Recruitment & Eligibility
- Status
- NOT_YET_RECRUITING
- Sex
- All
- Target Recruitment
- 45
- Age ≥18 years
- Confirmed or suspected infection (pathogen detected or antimicrobial administered)
- SOFA score ≥2
- ICU patient or ED patient with anticipated ICU admission
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Experimental: FFP Bolus Fresh Frozen Plasma (blood product) Two-unit initial FFP bolus, then one unit every 12 hours for 48 hours (total 5 units). Experimental: FFP Continuous Infusion Fresh Frozen Plasma (blood product) 5 units FFP infused continuously at \~42 mL/hr over 48 hours. Placebo Comparator: Lactated Ringer's + Multivitamins MVI and lactated ringers Placebo given as either (a) 500 mL LR bolus, then 250 mL q12h for 48h (total 1,250 mL), or (b) 500 mL over 12h, repeated to total 2,000 mL over 48h; prepared by pharmacy to match plasma appearance.
- Primary Outcome Measures
Name Time Method Syndecan-1 baseline to study days 1,3,5 Syndecan-1 measurement
- Secondary Outcome Measures
Name Time Method 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).
SOFA Score change over days 1, 3, 5 SOFA score