Study Assessing Efficacy of Plasmatherapy in Septic Shock-induced Coagulopathy: Feasibility Study (PlasmaFaisa)

Prospective Randomized Versus Placebo Study Assessing Efficacy of Plasmatherapy in Septic Shock-induced Coagulopathy: Feasibility Study

No randomized controlled trial (RCT) has investigated the effect of prophylactic fresh frozen plasma (FFP) transfusion in septic or critically ill patients with coagulation abnormalities. The last Surviving Sepsis Campaign therefore suggests with a very low quality of evidence "against the use of fresh frozen plasma during septic shock to correct clotting abnormalities in the absence of bleeding or planned invasive procedures". However, expert opinion highlights that FFP should be transfused "when there is a documented deficiency of coagulation factors (increased prothrombin time, international normalized ratio - INR, or partial thromboplastin time) and the presence of active bleeding or before surgical or invasive procedures". Disseminated intravascular coagulation (DIC) is responsible for such a severe deficiency of coagulation factors. Supplementing the intense deficit of coagulation factors with plasma containing non-activated coagulation factors is therefore a rational therapy in DIC patients.

OctaplasLG® is a donor plasma product, with unique features compared to standard fresh frozen plasma: standardized concentrations of natural pro-/anti-coagulation factors; a standardized volume; pathogen free. OctaplasLG® should reduce the "inflammatory hit" on the endothelium, including the glycocalyx, by having standardized levels of coagulation proteins, which can give more sustainable support to the endothelial regeneration as compared to standard fresh frozen plasma.

Study Overview

• Status: Completed
• Conditions: Septic Shock; Coagulopathy; Disseminated Intravascular Coagulation
• Intervention / Treatment: Drug: OctaplasLG®; Drug: 0.9% NaCl

Detailed Description

The present RCT is an open-label faisability study. OctaplasLG® or a placebo (0.9% NaCl) will be allocated to patients with a septic shock-induced coagulopathy defined by decreased platelets (<150,000/mm3 or >30% decrease within 24 hours) and an INR>1.40, and started within the 6 hours following coagulopathy diagnosis.

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Julie Helms, MD; Phone Number: 0033 03 69 55 04 34; Email: julie.helms@chru-strasbourg.fr

Study Locations

• France
  • Strasbourg, France, 67000
    • Hopitaux Universitaires de Strasbourg

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:

• Patient with:

  • a septic shock defined by Sepsis-3 criteria (Singer, JAMA 2016)
  • and a coagulopathy assessed by decreased platelets (<150,000/mm3 or >30% decrease within 24 hours) and an INR>1.40 (Vincent, Crit Care Med 2013) without other etiology
• Randomization within a timeframe of 6 hours after coagulopathy diagnosis
• Age strictly over 18 years old
• Subject affiliated to a social health insurance
• Free and informed consent dated and signed.

Exclusion Criteria:

• Contraindication to OctaplasLG®
• Contraindication to preventive anticoagulation by heparin
• Any disorder with a requirement for full anticoagulation on the day of randomization
• PT prolongation or thrombocytopenia that is not due to sepsis
• History of congenital bleeding disorder predisposing to hemorrhage
• Medical condition associated with a hypercoagulable state
• Patient moribund on the day of randomization
• Do not resuscitate limitation at inclusion in the study
• Law protection: guardianship or curatorship
• Pregnancy/breastfeeding

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Experimental group; The experimental group will receive 12 ml/kg of OctaplasLG® at day 1, within the 2 hours after randomization (i.e. within the 8 hours after coagulopathy diagnosis). A new identical dose will be infused at day 2 according to coagulation parameters. OctaplasLG® is a donor plasma product, with unique features compared to standard fresh frozen plasma: standardized concentrations of natural pro-/anti-coagulation factors; a standardized volume; pathogen free. OctaplasLG® should reduce the "inflammatory hit" on the endothelium, including the glycocalyx, by having standardized levels of coagulation proteins, which can give more sustainable support to the endothelial regeneration as compared to standard fresh frozen plasma.	Drug: OctaplasLG®; Patient receive 12 ml/kg of OctaplasLG® at day 1, within the 2 hours after randomization (i.e. within the 8 hours after coagulopathy diagnosis). A new identical dose will be infused at day 2 according to coagulation parameters.
Placebo Comparator: Control group; The control group will receive 12 ml/kg of placebo (0.9% NaCl) at day 1, within the 2 hours after randomization (i.e. within the 8 hours after coagulopathy diagnosis). A new identical dose will be infused at day 2 according to coagulation parameters.	Drug: 0.9% NaCl; Patient receive 12 ml/kg of placebo (0.9% NaCl) at day 1, within the 2 hours after randomization (i.e. within the 8 hours after coagulopathy diagnosis). A new identical dose will be infused at day 2 according to coagulation parameters.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
delays between the diagnosis of coagulopathy and the administration of treatment	Day 2

Secondary Outcome Measures

Outcome Measure	Time Frame
Mortality	Day 7
SOFA	Day 7

Collaborators and Investigators

• Sponsor: University Hospital, Strasbourg, France
• Investigators: Principal Investigator: Julie HELMS, MD, Hopitaux Universitaires de Strasbourg

Study record dates

Study Major Dates

• Study Start (Actual): October 22, 2020
• Primary Completion (Actual): December 9, 2022
• Study Completion (Actual): January 3, 2023

Study Registration Dates

• First Submitted: September 24, 2020
• First Submitted That Met QC Criteria: October 7, 2020
• First Posted (Actual): October 8, 2020

Study Record Updates

• Last Update Posted (Actual): January 5, 2023
• Last Update Submitted That Met QC Criteria: January 4, 2023
• Last Verified: January 1, 2023

More Information

Terms related to this study

• Keywords: septic shock; coagulopathy; disseminated intravascular coagulation; - plasmatherapy
• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Hematologic Diseases; Hemorrhagic Disorders; Sepsis; Thrombophilia; Hemostatic Disorders; Blood Coagulation Disorders; Shock, Septic; Shock; Disseminated Intravascular Coagulation
• Other Study ID Numbers: 7572

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