Clinical trial NCT03092245: Vasculopathic Injury and Plasma as Endothelial Rescue in Septic Shock (SHOCK) Trial
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: COMPLETED
Phase: PHASE2
Conditions: Septic Shock
Lead sponsor: Rigshospitalet, Denmark
Sponsor class: OTHER
Collaborators: name: Octapharma
name: University of Iceland
First posted: 2017-03-27
Enrollment: 44
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: This is a single center, randomized (1:1, active : standard of care), controlled, open-label, investigator-initiated pilot phase IIa trial in patients with septic shock investigating the efficacy and safety of administrating OctaplasLG® as compared to crystalloids, such as Ringer-Acetate (standard of care) in a total of 40 patients.

40 patients will be enrolled:

* Patients in the active treatment group (n = 20 patients) will receive OctaplasLG® as volume support according to trial algorithm.
* Patients in the standard of care group (n = 20 patients) will receive crystalloids, such as Ringer-Acetate, as volume support according to trial algorithm.

All patients will be treated according to the standard ICU care.

Eligibility criteria: Inclusion Criteria:

1. Adult intensive care patients (age ≥ 18 years) AND
2. Sepsis, defined as life-threatening organ dysfunction caused by a dysregulated host response to infection AND
3. Quick SOFA (qSOFA) with two or more of

   1. Respiratory rate ≥ 22/min
   2. Altered mentation (Glasgow Coma Scale score \< 15)
   3. Systolic blood pressure ≤ 100mmHg AND
4. Septic shock, defined as a clinical construct of sepsis with persisting hypotension requiring vasopressors to maintain MAP ≥65 mm Hg and having a serum lactate level \>2 mmol/L despite adequate volume resuscitation AND
5. Requiring infusion of noradrenalin 0.10 mcg/kg/min or more to maintain blood pressure AND
6. Respiratory failure requiring intubation and mechanical ventilation

Exclusion Criteria:

1. Documented refusal of blood transfusion OR
2. Treatment with GPIIb/IIIa inhibitors \< 24h from screening OR
3. Withdrawal from active therapy OR
4. Previously within 30 days included in an interventional trial OR
5. Known IgA deficiency with documented antibodies against IgA OR
6. 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
7. Known severe deficiencies of protein S OR
8. Pregnancy (non-pregnancy confirmed by patient being postmenopausal or having a negative urine-hCG) OR
9. Severe cirrhotic hepatic failure with expected need for treatment with terlipressin

Primary outcomes:
measure: Microscan at 24 hours
timeFrame: 24 hours after baseline
measure: Biomarkers at 24 hours
timeFrame: 24 hours after baseline
Secondary outcomes:
measure: 24 hour mortality
timeFrame: 24 hours after inclusion
measure: 7 day mortality
timeFrame: 7 days after inclusion
measure: 30 day mortality
timeFrame: 30 days after inclusion
measure: 90 day mortality
timeFrame: 90 days after inclusion
measure: Length of stay in the ICU
timeFrame: Days, assessed at 30-days and 90-days
measure: Days on vasopressors
timeFrame: Days, assessed at 30-days and 90-days
measure: Days on ventilator
timeFrame: Days, assessed at 30-days and 90-days
measure: Transfusion requirements
timeFrame: For the first 7 days after inclusion
measure: Serious Adverse Reactions at 72 hours
timeFrame: For the first 72 hours after inclusion
measure: Serious Adverse Reactions at day 30
timeFrame: At day 30 after inclusion
measure: Oxygenation
timeFrame: At 24 hours, 48 hours, 72 hours and at day 7 after baseline
measure: RIFLE criteria: Risk, Injury, and Failure, Loss and End-stage kidney disease
timeFrame: For the first 7 days in the ICU
measure: Renal Replacement Therapy
timeFrame: For the first 7 days after inclusion
Other outcomes:
measure: Sepsis-related organ failure assessment (SOFA)
timeFrame: At 24 hours, 48 hours, 72 hours and at day 7 after baseline
measure: Thrombelastograph (TEG) maximum amplitude at 24 hours
timeFrame: At 24 hours after baseline
measure: Thrombelastograph (TEG) maximum amplitude at 48 hours
timeFrame: At 48 hours after baseline
measure: Thrombelastograph (TEG) maximum amplitude at 72 hours
timeFrame: At 72 hours after baseline
measure: Thrombelastograph (TEG) Functional Fibrinogen maximum amplitude at 24 hours
timeFrame: At 24 hours after baseline
measure: Thrombelastograph (TEG) Functional Fibrinogen maximum amplitude at 48 hours
timeFrame: At 48 hours after baseline
measure: Thrombelastograph (TEG) Functional Fibrinogen maximum amplitude at 72 hours
timeFrame: At 72 hours after baseline
measure: Disseminated Intravascular Coagulation (DIC) score
timeFrame: At 24 hours, 48 hours, 72 hours and at day 7 after baseline
Locations:
city: Copenhagen
country: Denmark
facility: ICU Bispebjerg Hospital
Study officials:
affiliation: Bispebjerg and Frederiksberg Hospitals, Capitol Region of Copenhagen
name: Niels E Clausen
role: PRINCIPAL_INVESTIGATOR
References: