Vasculopathic Injury and Plasma as Endothelial Rescue in Septic Shock Trial. VIPER-Sepsis (EudraCT no. 2016-000707-81)
- Conditions
- Septic Shock
- Interventions
- Drug: Ringer-acetatDrug: OctaplasLG®
- Registration Number
- NCT02875236
- Lead Sponsor
- Rigshospitalet, Denmark
- Brief Summary
Efficacy and safety of octaplasLG® administration vs. crystalloids (standard) in patients with septic shock - a randomized, controlled, open-label investigator-initiated pilot trial.
- Detailed Description
Recently a great interest in the role of the endothelium in the pathophysiology of sepsis has been introduced. The endothelium is coated by a "thick" endothelial glycocalyx protecting it from becoming activated and prevents capillary leakage. The glycocalyx binds approximately 1-1.5 litres of the plasma portion of the circulating blood and regulates the dynamic exchange between the intra -and extravascular space, therefore, functioning both as a barrier and as a mechano transducer. Damage to the glycocalyx is caused by major trauma, major surgery, or ischemia and reperfusion injury, and resulting in vascular leakage. Damage to the endothelium is further augmented by resuscitation of crystalloids and colloids as well as related to bleeding. Thawed fresh frozen plasma may cause a further "inflammatory hit" towards the glycocalyx and endothelium. The degradation of the glycocalyx increases endothelial permeability with edema formation entitled 'the endothelial leakage syndrome', and resulting in the development of hypotension, pulmonary complications, abdominal compartment syndrome, multi-organ failure and death.
The current strategy for maintaining the intravascular volume in patients with acute critical illness focuses on the administration of crystalloids, such as Ringer-Acetate, and natural colloids. Crystalloids, especially, are known to extravasate and cause edema, which is associated with hypoperfusion and compromised vital organ function by the increased tissue pressure that limits oxygen delivery, and ultimately leading to the complications described above. Until recently, synthetic colloids were the preferred choice of fluids for these patients, but a Scandinavian study in patients with severe sepsis and septic shock (6S trial) demonstrated an increased mortality in patients receiving synthetic colloids, thereby, establishing the adverse effect of such a strategy. Consequently, new resuscitation fluids are needed, preferably not only to support the intravascular volume, but also to support and restore the endothelial integrity.
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 5
- Adult intensive care patients AND
- Septic shock requiring infusion of vasopressor/inotropic agents to maintain blood pressure as defined in international guidelines AND
- Consent obtainable from patient or by proxy (independent physicians and/or next of kin)
- Documented refusal of blood transfusion OR
- Treatment with GPIIb/IIIa inhibitors < 24h from screening OR
- Withdrawal from active therapy OR
- Previously within 30 days included in a randomised trial, if known at the time of enrolment OR
- Known Immunoglobulin A deficiency with documented antibodies against Immunoglobulin A OR
- Known hypersensitivity to OctaplasLG: the active substance, any of the excipients (Sodium citrate dihydrate, Sodium dihydrogenphosphate dihydrate or Glycine) or residues from the manufacturing process (Tri (N-Butyl) Phosphate (TNBP) and Octoxynol (Triton X-100)) OR
- Known severe deficiencies of protein S OR
- Pregnancy (non-pregnancy confirmed by patient being postmenopausal or having a negative urine-hCG) OR
- Severe cirrhotic hepatic failure with expected need for treatment with terlipressin
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- FACTORIAL
- Arm && Interventions
Group Intervention Description Intervention Ringer-acetat OctaplasLG® Control OctaplasLG® Ringer-acetat
- Primary Outcome Measures
Name Time Method Microvascular perfusion 6 hours after inclusion Change in microvascular perfusion as evaluated by sidestream darkfield (SDF; MicroVision Medical, Amsterdam, The Netherlands) imaging technique.
Endothelial activation and damage 6 hours after inclusion Change in biomarkers indicative of endothelial activation and damage (soluble E-selectin, syndecan-1, thrombomodulin, soluble VE-cadherin, nucleosomes)
- Secondary Outcome Measures
Name Time Method Bleeding 1 week Bleeding requiring \> 2 RBC / day
TRALI 30 days Transfusion Related Acute Lung Injury
Mortality From 6 hours until 90 days Difference in mortality between patients receiving active treatment (OctaplasLG®) and standard of care (crystalloids)
Ventilator through study completion, an average of 1 month Days on ventilator
Length of stay in Intensive Care Unit through study completion, an average of 1 month Length of stay in the Intensive Care Unit
Vasopressors through study completion, an average of 1 month Days on vasopressors
SAR 30 days Severe adverse reactions, defined as symptomatic thromboembolism
TACO 30 days Transfusion associated circulatory overload
Trial Locations
- Locations (1)
Intensive Care Unit Bispebjerg Hospital
🇩🇰Copenhagen, Denmark