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

• ClinicalTrials.gov Identifier: NCT04580563
• Recruitment Status: Active, not recruiting
• First Posted: October 8, 2020
• Last Update Posted: October 8, 2020
• Sponsor: University Hospital, Strasbourg, France
• Information provided by (Responsible Party): University Hospital, Strasbourg, France

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Septic Shock; Coagulopathy; Disseminated Intravascular Coagulation	Drug: OctaplasLG®; Drug: 0.9% NaCl	Not Applicable

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 Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 60 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Prospective Randomized Versus Placebo Study Assessing Efficacy of Plasmatherapy in Septic Shock-induced Coagulopathy: Feasibility Study
• Actual Study Start Date: September 4, 2020
• Estimated Primary Completion Date: June 2022
• Estimated Study Completion Date: June 2022

Arms and Interventions

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 if prothrombin time is below 50%. 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 if prothrombin time is below 50%.
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 if prothrombin time is below 50%.	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 if prothrombin time is below 50%.

Outcome Measures

Primary Outcome Measures :

1. delays between the diagnosis of coagulopathy and the administration of treatment [ Time Frame: Day 2 ]

Secondary Outcome Measures :

1. Mortality [ Time Frame: Day 7 ]
2. SOFA [ Time Frame: Day 7 ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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

Contacts and Locations

Locations

France

Hôpitaux Universitaires de Strasbourg

Strasbourg, France, 67000

Sponsors and Collaborators

University Hospital, Strasbourg, France

Investigators

• Principal Investigator: Julie HELMS, MD; Hôpitaux Universitaires de Strasbourg

More Information

• Responsible Party: University Hospital, Strasbourg, France
• ClinicalTrials.gov Identifier: NCT04580563
• Other Study ID Numbers: 7572
• First Posted: October 8, 2020
• Last Update Posted: October 8, 2020
• Last Verified: September 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by University Hospital, Strasbourg, France:

septic shock; coagulopathy; disseminated intravascular coagulation; - plasmatherapy

Additional relevant MeSH terms:

Shock, Septic; Hemostatic Disorders; Blood Coagulation Disorders; Disseminated Intravascular Coagulation; Shock; Pathologic Processes; Sepsis; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Hematologic Diseases; Vascular Diseases; Cardiovascular Diseases; Hemorrhagic Disorders; Thrombophilia