Vasculopathic Injury and Plasma as Endothelial Rescue in Septic Shock (SHOCK) Trial (VIPER-SHOCK)

Efficacy and Safety of OctaplasLG® Administration vs. Crystalloids (Standard) in Patients With Septic Shock - a Randomized, Controlled, Open-label Investigator-initiated Pilot Trial

Efficacy and safety of OctaplasLG® administration vs. crystalloids (standard) in patients with septic shock - a randomized, controlled, open-label investigator-initiated pilot trial

Study Overview

• Status: Completed
• Conditions: Septic Shock
• Intervention / Treatment: Drug: OctaplasLG; Drug: Ringer-Acetate

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.

• Study Type: Interventional
• Enrollment (Actual): 44
• Phase: Phase 2

Contacts and Locations

Study Locations

• Denmark
  • Copenhagen, Denmark, 2200
    • ICU Bispebjerg Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Factorial Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: OctaplasLG; OctaplasLG® is an industrial donor plasma product pooled from 630 -1520 single donor units. It possesses unique features when compared to standard FFP, such as having a standardized concentration of natural pro- and anti-coagulation factors, a standardized volume as well as being pathogen-free.12 Most importantly, the manufacturing method of OctaplasLG® removes immune complexes and cells in several steps of microfiltration. The manufacturing process also inactivates viral, bacterial and prion pathogen by immune neutralization, solvent-detergent treatment and a prion specific ligand affinity chromatography step.	Drug: OctaplasLG; OctaplasLG is given as an infusion when resuscitation fluids are required.; Other Names: Octaplas
Placebo Comparator: Ringer-Acetate; standard of care resuscitation fluid Ringer-acetate is a mixture of electrolytes in water to a slightly hypotonic solution.	Drug: Ringer-Acetate; Ringer-acetate is given as an infusion when resuscitation fluids are required.; Other Names: Ringer's Acetate

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Microscan at 24 hours	Change in microvascular perfusion from baseline to 24 hours after inclusion as evaluated by sidestream darkfield (SDF; MicroVision Medical, Amsterdam, The Netherlands) imaging technique.	24 hours after baseline
Biomarkers at 24 hours	Change in biomarkers indicative of endothelial activation and damage (sE-selectin, syndecan-1, thrombomodulin, VEGFR1, VEGF, nucleosomes) from baseline to 24 hours after inclusion.	24 hours after baseline

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
24 hour mortality	Difference in 24 hours mortality between patients receiving active treatment (OctaplasLG®) and standard of care (crystalloids such as Ringer-Acetate).	24 hours after inclusion
7 day mortality	Difference in 7 day mortality between patients receiving active treatment (OctaplasLG®) and standard of care (crystalloids such as Ringer-Acetate).	7 days after inclusion
30 day mortality	Difference in 30 day mortality between patients receiving active treatment (OctaplasLG®) and standard of care (crystalloids such as Ringer-Acetate).	30 days after inclusion
90 day mortality	Difference in 90 day mortality between patients receiving active treatment (OctaplasLG®) and standard of care (crystalloids such as Ringer-Acetate).	90 days after inclusion
Length of stay in the ICU	The number of days in the ICU after inclusion	Days, assessed at 30-days and 90-days
Days on vasopressors	The number of days on vasopressors after inclusion	Days, assessed at 30-days and 90-days
Days on ventilator	The number of days on vasopressors after inclusion	Days, assessed at 30-days and 90-days
Transfusion requirements	Bleeding requiring > 2 RBC / day	For the first 7 days after inclusion
Serious Adverse Reactions at 72 hours	Severe adverse reactions, defined as symptomatic thromboembolism and TACO/TRALI	For the first 72 hours after inclusion
Serious Adverse Reactions at day 30	Severe adverse reactions, defined as symptomatic thromboembolism and TACO/TRALI	At day 30 after inclusion
Oxygenation	As evaluated by the PaO2/FiO2-ratio during the ICU stay	At 24 hours, 48 hours, 72 hours and at day 7 after baseline
RIFLE criteria: Risk, Injury, and Failure, Loss and End-stage kidney disease	Acute Kidney Injury according to RIFLE criteria	For the first 7 days in the ICU
Renal Replacement Therapy	recording whether the patient is receiving dialysis or not	For the first 7 days after inclusion

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Sepsis-related organ failure assessment (SOFA)	Worst score in a 24 hour period	At 24 hours, 48 hours, 72 hours and at day 7 after baseline
Thrombelastograph (TEG) maximum amplitude at 24 hours	Measuring the maximum amplitude (MA) in mm with TEG	At 24 hours after baseline
Thrombelastograph (TEG) maximum amplitude at 48 hours	Measuring the maximum amplitude (MA) in mm with TEG	At 48 hours after baseline
Thrombelastograph (TEG) maximum amplitude at 72 hours	Measuring the maximum amplitude (MA) in mm with TEG	At 72 hours after baseline
Thrombelastograph (TEG) Functional Fibrinogen maximum amplitude at 24 hours	Measuring the maximum amplitude (MA) in mm with TEG Functional Fibrinogen (FF)	At 24 hours after baseline
Thrombelastograph (TEG) Functional Fibrinogen maximum amplitude at 48 hours	Measuring the maximum amplitude (MA) in mm with TEG Functional Fibrinogen (FF)	At 48 hours after baseline
Thrombelastograph (TEG) Functional Fibrinogen maximum amplitude at 72 hours	Measuring the maximum amplitude (MA) in mm with TEG Functional Fibrinogen (FF)	At 72 hours after baseline
Disseminated Intravascular Coagulation (DIC) score	Total score in a 24 hour period based upon platelets, INR, Fibrinogen and D-dimer lab results.	At 24 hours, 48 hours, 72 hours and at day 7 after baseline

Collaborators and Investigators

• Sponsor: Rigshospitalet, Denmark
• Collaborators: University of Iceland; Octapharma
• Investigators: Principal Investigator: Niels E Clausen, Bispebjerg and Frederiksberg Hospitals, Capitol Region of Copenhagen

Study record dates

Study Major Dates

• Study Start (Actual): April 18, 2017
• Primary Completion (Actual): April 17, 2019
• Study Completion (Actual): April 17, 2019

Study Registration Dates

• First Submitted: February 21, 2017
• First Submitted That Met QC Criteria: March 21, 2017
• First Posted (Actual): March 27, 2017

Study Record Updates

• Last Update Posted (Estimate): January 19, 2023
• Last Update Submitted That Met QC Criteria: January 18, 2023
• Last Verified: January 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Sepsis; Shock, Septic; Shock
• Other Study ID Numbers: VIPER-SHOCK; 2017-000427-27 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No