Septic Shock
Conditions
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.
Interventions
DRUGOctaplasLG
OctaplasLG is given as an infusion when resuscitation fluids are required.
DRUGRinger-Acetate
Ringer-acetate is given as an infusion when resuscitation fluids are required.
Sponsors
Octapharma
University of Iceland
Rigshospitalet, Denmark
Study design
Allocation
RANDOMIZED
Intervention model
FACTORIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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). |
| 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). |
| Days on vasopressors | 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 |
| Days on ventilator | Days, assessed at 30-days and 90-days | The number of days on vasopressors after inclusion |
| 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 |
| 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). |
Other
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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 |
Countries
Denmark
Outcome results
None listed