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

Primary Purpose

Septic Shock

Status

Completed

Phase

Phase 2

Locations

Denmark

Study Type

Interventional

Intervention

OctaplasLG

Ringer-Acetate

About this trial

This is an interventional treatment trial for Septic Shock

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Adult intensive care patients (age ≥ 18 years) AND
Sepsis, defined as life-threatening organ dysfunction caused by a dysregulated host response to infection AND
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
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
Requiring infusion of noradrenalin 0.10 mcg/kg/min or more to maintain blood pressure AND
Respiratory failure requiring intubation and mechanical ventilation

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 an interventional trial OR
Known IgA deficiency with documented antibodies against IgA 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

Sites / Locations

ICU Bispebjerg Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

OctaplasLG

Ringer-Acetate

Arm Description

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.

standard of care resuscitation fluid Ringer-acetate is a mixture of electrolytes in water to a slightly hypotonic solution.

Outcomes

Primary Outcome Measures

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.

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.

Secondary Outcome Measures

24 hour mortality

Difference in 24 hours mortality between patients receiving active treatment (OctaplasLG®) and standard of care (crystalloids such as Ringer-Acetate).

7 day mortality

Difference in 7 day mortality between patients receiving active treatment (OctaplasLG®) and standard of care (crystalloids such as Ringer-Acetate).

30 day mortality

Difference in 30 day mortality between patients receiving active treatment (OctaplasLG®) and standard of care (crystalloids such as Ringer-Acetate).

90 day mortality

Difference in 90 day mortality between patients receiving active treatment (OctaplasLG®) and standard of care (crystalloids such as Ringer-Acetate).

Length of stay in the ICU

The number of days in the ICU after inclusion

Days on vasopressors

The number of days on vasopressors after inclusion

Days on ventilator

The number of days on vasopressors after inclusion

Transfusion requirements

Bleeding requiring > 2 RBC / day

Serious Adverse Reactions at 72 hours

Severe adverse reactions, defined as symptomatic thromboembolism and TACO/TRALI

Serious Adverse Reactions at day 30

Severe adverse reactions, defined as symptomatic thromboembolism and TACO/TRALI

Oxygenation

As evaluated by the PaO2/FiO2-ratio during the ICU stay

RIFLE criteria: Risk, Injury, and Failure, Loss and End-stage kidney disease

Acute Kidney Injury according to RIFLE criteria

Renal Replacement Therapy

recording whether the patient is receiving dialysis or not

Full Information

NCT ID

NCT03092245

First Posted

February 21, 2017

Last Updated

January 18, 2023

Sponsor

Rigshospitalet, Denmark

Collaborators

Octapharma, University of Iceland

1. Study Identification

Unique Protocol Identification Number

NCT03092245

Brief Title

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

Acronym

VIPER-SHOCK

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

2. Study Status

Record Verification Date

January 2023

Overall Recruitment Status

Completed

Study Start Date

April 18, 2017 (Actual)

Primary Completion Date

April 17, 2019 (Actual)

Study Completion Date

April 17, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Rigshospitalet, Denmark

Collaborators

Octapharma, University of Iceland

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Septic Shock

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Factorial Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

44 (Actual)

8. Arms, Groups, and Interventions

Arm Title

OctaplasLG

Arm Type

Active Comparator

Arm Description

Arm Title

Ringer-Acetate

Arm Type

Placebo Comparator

Arm Description

standard of care resuscitation fluid Ringer-acetate is a mixture of electrolytes in water to a slightly hypotonic solution.

Intervention Type

Drug

Intervention Name(s)

OctaplasLG

Other Intervention Name(s)

Octaplas

Intervention Description

OctaplasLG is given as an infusion when resuscitation fluids are required.

Intervention Type

Drug

Intervention Name(s)

Ringer-Acetate

Other Intervention Name(s)

Ringer's Acetate

Intervention Description

Ringer-acetate is given as an infusion when resuscitation fluids are required.

Primary Outcome Measure Information:

Title

Microscan at 24 hours

Description

Change in microvascular perfusion from baseline to 24 hours after inclusion as evaluated by sidestream darkfield (SDF; MicroVision Medical, Amsterdam, The Netherlands) imaging technique.

Time Frame

24 hours after baseline

Title

Biomarkers at 24 hours

Description

Change in biomarkers indicative of endothelial activation and damage (sE-selectin, syndecan-1, thrombomodulin, VEGFR1, VEGF, nucleosomes) from baseline to 24 hours after inclusion.

Time Frame

24 hours after baseline

Secondary Outcome Measure Information:

Title

24 hour mortality

Description

Difference in 24 hours mortality between patients receiving active treatment (OctaplasLG®) and standard of care (crystalloids such as Ringer-Acetate).

Time Frame

24 hours after inclusion

Title

7 day mortality

Description

Difference in 7 day mortality between patients receiving active treatment (OctaplasLG®) and standard of care (crystalloids such as Ringer-Acetate).

Time Frame

7 days after inclusion

Title

30 day mortality

Description

Difference in 30 day mortality between patients receiving active treatment (OctaplasLG®) and standard of care (crystalloids such as Ringer-Acetate).

Time Frame

30 days after inclusion

Title

90 day mortality

Description

Difference in 90 day mortality between patients receiving active treatment (OctaplasLG®) and standard of care (crystalloids such as Ringer-Acetate).

Time Frame

90 days after inclusion

Title

Length of stay in the ICU

Description

The number of days in the ICU after inclusion

Time Frame

Days, assessed at 30-days and 90-days

Title

Days on vasopressors

Description

The number of days on vasopressors after inclusion

Time Frame

Days, assessed at 30-days and 90-days

Title

Days on ventilator

Description

The number of days on vasopressors after inclusion

Time Frame

Days, assessed at 30-days and 90-days

Title

Transfusion requirements

Description

Bleeding requiring > 2 RBC / day

Time Frame

For the first 7 days after inclusion

Title

Serious Adverse Reactions at 72 hours

Description

Severe adverse reactions, defined as symptomatic thromboembolism and TACO/TRALI

Time Frame

For the first 72 hours after inclusion

Title

Serious Adverse Reactions at day 30

Description

Severe adverse reactions, defined as symptomatic thromboembolism and TACO/TRALI

Time Frame

At day 30 after inclusion

Title

Oxygenation

Description

As evaluated by the PaO2/FiO2-ratio during the ICU stay

Time Frame

At 24 hours, 48 hours, 72 hours and at day 7 after baseline

Title

RIFLE criteria: Risk, Injury, and Failure, Loss and End-stage kidney disease

Description

Acute Kidney Injury according to RIFLE criteria

Time Frame

For the first 7 days in the ICU

Title

Renal Replacement Therapy

Description

recording whether the patient is receiving dialysis or not

Time Frame

For the first 7 days after inclusion

Other Pre-specified Outcome Measures:

Title

Sepsis-related organ failure assessment (SOFA)

Description

Worst score in a 24 hour period

Time Frame

At 24 hours, 48 hours, 72 hours and at day 7 after baseline

Title

Thrombelastograph (TEG) maximum amplitude at 24 hours

Description

Measuring the maximum amplitude (MA) in mm with TEG

Time Frame

At 24 hours after baseline

Title

Thrombelastograph (TEG) maximum amplitude at 48 hours

Description

Measuring the maximum amplitude (MA) in mm with TEG

Time Frame

At 48 hours after baseline

Title

Thrombelastograph (TEG) maximum amplitude at 72 hours

Description

Measuring the maximum amplitude (MA) in mm with TEG

Time Frame

At 72 hours after baseline

Title

Thrombelastograph (TEG) Functional Fibrinogen maximum amplitude at 24 hours

Description

Measuring the maximum amplitude (MA) in mm with TEG Functional Fibrinogen (FF)

Time Frame

At 24 hours after baseline

Title

Thrombelastograph (TEG) Functional Fibrinogen maximum amplitude at 48 hours

Description

Measuring the maximum amplitude (MA) in mm with TEG Functional Fibrinogen (FF)

Time Frame

At 48 hours after baseline

Title

Thrombelastograph (TEG) Functional Fibrinogen maximum amplitude at 72 hours

Description

Measuring the maximum amplitude (MA) in mm with TEG Functional Fibrinogen (FF)

Time Frame

At 72 hours after baseline

Title

Disseminated Intravascular Coagulation (DIC) score

Description

Total score in a 24 hour period based upon platelets, INR, Fibrinogen and D-dimer lab results.

Time Frame

At 24 hours, 48 hours, 72 hours and at day 7 after baseline

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Adult intensive care patients (age ≥ 18 years) AND Sepsis, defined as life-threatening organ dysfunction caused by a dysregulated host response to infection AND Quick SOFA (qSOFA) with two or more of Respiratory rate ≥ 22/min Altered mentation (Glasgow Coma Scale score < 15) Systolic blood pressure ≤ 100mmHg AND 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 Requiring infusion of noradrenalin 0.10 mcg/kg/min or more to maintain blood pressure AND Respiratory failure requiring intubation and mechanical ventilation 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 an interventional trial OR Known IgA deficiency with documented antibodies against IgA 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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Niels E Clausen

Organizational Affiliation

Bispebjerg and Frederiksberg Hospitals, Capitol Region of Copenhagen

Official's Role

Principal Investigator

Facility Information:

Facility Name

ICU Bispebjerg Hospital

City

Copenhagen

ZIP/Postal Code

2200

Country

Denmark

12. IPD Sharing Statement

Plan to Share IPD

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

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