Clinical trial NCT02875236: Vasculopathic Injury and Plasma as Endothelial Rescue in Septic Shock Trial. VIPER-Sepsis (EudraCT no. 2016-000707-81)
Official title: Efficacy and Safety of OctaplasLG Administration vs. Crystalloids (Standard) in Patients With Septic Shock - a Randomized, Controlled, Open-label Investigator-initiated Pilot Trial
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE4
Conditions: Septic Shock
Lead sponsor: Rigshospitalet, Denmark
Sponsor class: OTHER
Collaborators: name: Octapharma
First posted: 2016-08-23
Enrollment: 5
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: FACTORIAL
Primary purpose: TREATMENT

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.

Eligibility criteria: Inclusion Criteria:

* 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)

Exclusion Criteria:

* 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

Primary outcomes:
measure: Microvascular perfusion
timeFrame: 6 hours after inclusion
measure: Endothelial activation and damage
timeFrame: 6 hours after inclusion
Secondary outcomes:
measure: Mortality
timeFrame: From 6 hours until 90 days
measure: Length of stay in Intensive Care Unit
timeFrame: through study completion, an average of 1 month
measure: Vasopressors
timeFrame: through study completion, an average of 1 month
measure: Ventilator
timeFrame: through study completion, an average of 1 month
measure: Bleeding
timeFrame: 1 week
measure: SAR
timeFrame: 30 days
measure: TACO
timeFrame: 30 days
measure: TRALI
timeFrame: 30 days
Other outcomes:
measure: SOFA score
timeFrame: 7 days
measure: AKI
timeFrame: 7 days
measure: CRRT
timeFrame: 7 days
measure: TEG
timeFrame: 72 hours
measure: DIC
timeFrame: 7 days
Locations:
city: Copenhagen
country: Denmark
facility: Intensive Care Unit Bispebjerg Hospital
Study officials:
affiliation: University of Copenhagen, Rigshospitalet, Denmark
name: Per I Johansson, MD
role: STUDY_DIRECTOR
References: