VIPER-SHOCK: Vasculopathic Injury and Plasma as Endothelial Rescue in Septic Shock (SHOCK) Trial
Study Details
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
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 2 |
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:
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Patients in the active treatment group (n = 20 patients) will receive OctaplasLG® as volume support according to trial algorithm.
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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 Design
Arms and Interventions
| 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:
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| 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:
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Outcome Measures
Primary Outcome Measures
- Microscan at 24 hours [24 hours after baseline]
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 [24 hours after baseline]
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 [24 hours after inclusion]
Difference in 24 hours mortality between patients receiving active treatment (OctaplasLG®) and standard of care (crystalloids such as Ringer-Acetate).
- 7 day mortality [7 days after inclusion]
Difference in 7 day mortality between patients receiving active treatment (OctaplasLG®) and standard of care (crystalloids such as Ringer-Acetate).
- 30 day mortality [30 days after inclusion]
Difference in 30 day mortality between patients receiving active treatment (OctaplasLG®) and standard of care (crystalloids such as Ringer-Acetate).
- 90 day mortality [90 days after inclusion]
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 [Days, assessed at 30-days and 90-days]
The number of days in the ICU after inclusion
- Days on vasopressors [Days, assessed at 30-days and 90-days]
The number of days on vasopressors after inclusion
- Days on ventilator [Days, assessed at 30-days and 90-days]
The number of days on vasopressors after inclusion
- Transfusion requirements [For the first 7 days after inclusion]
Bleeding requiring > 2 RBC / day
- Serious Adverse Reactions at 72 hours [For the first 72 hours after inclusion]
Severe adverse reactions, defined as symptomatic thromboembolism and TACO/TRALI
- Serious Adverse Reactions at day 30 [At day 30 after inclusion]
Severe adverse reactions, defined as symptomatic thromboembolism and TACO/TRALI
- Oxygenation [At 24 hours, 48 hours, 72 hours and at day 7 after baseline]
As evaluated by the PaO2/FiO2-ratio during the ICU stay
- RIFLE criteria: Risk, Injury, and Failure, Loss and End-stage kidney disease [For the first 7 days in the ICU]
Acute Kidney Injury according to RIFLE criteria
- Renal Replacement Therapy [For the first 7 days after inclusion]
recording whether the patient is receiving dialysis or not
Other Outcome Measures
- Sepsis-related organ failure assessment (SOFA) [At 24 hours, 48 hours, 72 hours and at day 7 after baseline]
Worst score in a 24 hour period
- Thrombelastograph (TEG) maximum amplitude at 24 hours [At 24 hours after baseline]
Measuring the maximum amplitude (MA) in mm with TEG
- Thrombelastograph (TEG) maximum amplitude at 48 hours [At 48 hours after baseline]
Measuring the maximum amplitude (MA) in mm with TEG
- Thrombelastograph (TEG) maximum amplitude at 72 hours [At 72 hours after baseline]
Measuring the maximum amplitude (MA) in mm with TEG
- Thrombelastograph (TEG) Functional Fibrinogen maximum amplitude at 24 hours [At 24 hours after baseline]
Measuring the maximum amplitude (MA) in mm with TEG Functional Fibrinogen (FF)
- Thrombelastograph (TEG) Functional Fibrinogen maximum amplitude at 48 hours [At 48 hours after baseline]
Measuring the maximum amplitude (MA) in mm with TEG Functional Fibrinogen (FF)
- Thrombelastograph (TEG) Functional Fibrinogen maximum amplitude at 72 hours [At 72 hours after baseline]
Measuring the maximum amplitude (MA) in mm with TEG Functional Fibrinogen (FF)
- Disseminated Intravascular Coagulation (DIC) score [At 24 hours, 48 hours, 72 hours and at day 7 after baseline]
Total score in a 24 hour period based upon platelets, INR, Fibrinogen and D-dimer lab results.
Eligibility Criteria
Criteria
Inclusion Criteria:
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Adult intensive care patients (age ≥ 18 years) AND
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Sepsis, defined as life-threatening organ dysfunction caused by a dysregulated host response to infection AND
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Quick SOFA (qSOFA) with two or more of
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Respiratory rate ≥ 22/min
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Altered mentation (Glasgow Coma Scale score < 15)
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Systolic blood pressure ≤ 100mmHg AND
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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
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Requiring infusion of noradrenalin 0.10 mcg/kg/min or more to maintain blood pressure AND
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Respiratory failure requiring intubation and mechanical ventilation
Exclusion Criteria:
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Documented refusal of blood transfusion OR
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Treatment with GPIIb/IIIa inhibitors < 24h from screening OR
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Withdrawal from active therapy OR
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Previously within 30 days included in an interventional trial OR
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Known IgA deficiency with documented antibodies against IgA OR
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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
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Known severe deficiencies of protein S OR
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Pregnancy (non-pregnancy confirmed by patient being postmenopausal or having a negative urine-hCG) OR
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Severe cirrhotic hepatic failure with expected need for treatment with terlipressin
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | ICU Bispebjerg Hospital | Copenhagen | Denmark | 2200 |
Sponsors and Collaborators
- Rigshospitalet, Denmark
- Octapharma
- University of Iceland
Investigators
- Principal Investigator: Niels E Clausen, Bispebjerg and Frederiksberg Hospitals, Capitol Region of Copenhagen
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- VIPER-SHOCK
- 2017-000427-27