Septic shock
Conditions
Interventions
Trade Name: OctaplasLG
Pharmaceutical Form: Solution for infusion
Pharmaceutical form of the placebo: Solution for injection
Route of administration of the placebo: Intravenous use
Sponsors
Hôpitaux Universitaires de Strasbourg
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Patient (male or female) with it: o Sepsis-3 septic shock (Singer, JAMA 2016): a patient with life-threatening acute organic dysfunction caused by an abnormal body response to infection (sepsis), requiring a vasopressor to maintain an average blood pressure of 65 mmHg or more, and a serum lactate level greater than 2 mmol / L (> 18 mg / dL) in the absence of hypovolemia o and coagulopathy defined by a decrease in the number of platelets ( 30% within 24 hours) and an INR> 1.40 (Vincent et al., JAMA 2019). - Randomization within 6 hours after diagnosis of coagulopathy - Age = 18 years at the time of signing the consent - Subject affiliated to a social health insurance - Free and informed consent dated and signed: o by the patient o or by a relative in the event that the patient is unable to express his or her consent o or inclusion in emergency procedure if the patient is not in a position to express consent and if no family member is available Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 50 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 10
Exclusion criteria
Exclusion criteria: - Contraindication to OctaplasLG®: o IgA deficiency with anti-IgA antibodies o Hypersensitivity to the active substance or to any of the excipients mentioned in section 6.1 or to residues from the manufacturing process o severe protein S deficiency - Contraindication to preventive anticoagulation with heparin (e. g. heparin-induced thrombocytopenia) - Any disorder requiring curative anticoagulation on the day of randomization - Prolongation of PD or thrombocytopenia not due to sepsis (e.g., AML or LAL induction therapy, myeloablative therapy within 4 weeks of enrolment, acute M3 leukemia, Child-Pugh class C cirrhosis) - History of congenital bleeding predisposing to bleeding (e.g., hemophilia) - Any known state of hypercoagulability, including: o Resistance to activated protein C or known Leiden factor V o Inherited protein C or protein S deficiency o Presence of anticardiolipin antibodies, antiphospholipid antibodies or mutation of the prothrombin gene - Cardiogenic shock - Acute left ventricular failure with pulmonary edema - Dying patient on the day of randomization - Limitation of active therapies at the time of inclusion in the study - Guardianship or guardianship or protection of justice - Pregnancy / breastfeeding.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary end point(s): Evaluation of the time between the diagnosis of coagulopathy and randomization (allocation of the "experimental" or "control" group) and the time between randomization and initiation of treatment. These time frames will allow the estimation of the rate of patients who have had randomization within 6 hours of the diagnosis of coagulopathy and the administration of treatment within 2 hours of randomization;Timepoint(s) of evaluation of this end point: Day 1;Main Objective: Assess the feasibility of randomizing the patient and administering treatment within the predefined time frame (randomization within 6 hours of the diagnosis of coagulopathy and administration of treatment within 2 hours of randomization).;Secondary Objective: - Evaluate refusals to participate - Estimate occurrence of the criteria of interest (below) in the experimental group receiving OctaplasLG® plasma therapy and in the control group receiving placebo infusion: 1. resolution of coagulopathy and inflammation during first 7d 2. mortality at 7, 28, 90d 3. duration of vasopressor treatment during first 28d 4. duration of mechanical ventilation during first 28d of the intensive care unit stay 5. duration of the stay in intensive care and hospital 6. occurrence of thrombotic complications within first 28d after inclusion 7. major bleeding during first 28da 8. organ failure during first 7d of the intensive care unit stay. - Estimate efficacy of OctaplasLG® as an adjuvant treatment for coagulopathy induced by septic shock compared to placebo on all criteria of interest. - Evaluate safety of OctaplasLG® in patients with complicated septic shock due to coagulopathy - Assess risk of hydrosodium overload in both groups. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): -Rates of patients for whom a refusal to participate has been notified (by the patient directly or by a relative in the event that the patient is unable to express consent) 1. resolution of coagulopathy and inflammation within the first 7 days: A D1, D2, D3, D4 and D7 after inclusion: a. Coagulation parameters: antithrombin, platelet count, prothrombin time, D-dimers, fibrinogen, coagulation factors (II, V, VII, X), PAI-1, TAFI, tissue thromboplastin b. Endothelial activation, inflammation and immune markers: circulating endothelial cells, leukocyte count, CD105+ endothelial microvesicles, CD66+ neutrophilic microvesicles, NEUT-SLF, HLA-DR. c. Endothelial integrity, glycocalyx markers, syndecan-1 level, ADAMTS-13. Mortality rates: assessed on days 7, 28 and 90 Duration of vasopressor treatment: number of days of vasopressors on day 28 after inclusion. 4. duration of mechanical ventilation: number of days of invasive and non-invasive ventilation on day 28 after inclusion Duration of stay in intensive care unit and hospital: number of days in intensive care unit and hospital 90 days after inclusion 6. occurrence of thrombotic complications (deep vein thrombosis, pulmonary embolism, post-thrombotic syndrome, superficial thrombophlebitis, stroke and myocardial infarction)[during the first 28 days after inclusion] : clinical data, laboratory results, ECG data and medical imaging results (CT, Doppler, coronary angiography, etc.) Occurrence of major bleeding[during the first 28 days after inclusion]: intracranial bleeding, life-threatening bleeding, any bleeding episode classified as severe by the investigator and administration of at least 6 units of red blood cells for 2 consecutive days. a. Transfusion requirements[for the first 7 days after inclusion] : concentrated red blood cell pellets, platelet concentrates, fresh frozen plasma, fibrinogen for the first 28 days b. Embolization / endoscopic treatment / surgical treatment of a bl | — |
Countries
France
Contacts
Public ContactEric DEMONSANT
Hôpitaux Universiatires de Strasbourg
Outcome results
None listed