Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Pre-hospital Administration of Lyophilized Plasma for Post-traumatic Coagulopathy Treatment (PREHO-PLYO) (PREHO-PLYO)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02736812
Recruitment Status : Completed
First Posted : April 13, 2016
Last Update Posted : January 7, 2020
Sponsor:
Collaborators:
Bataillon des marins pompiers de Marseille, France
Military Hospital Laveran,Marseille, France
Samu of Marseille, France
Samu of Lyon, France
Lyon-South Hospital, France
Hôpital Edouard Herriot
Fire Brigade Of Paris Emergency Medicine Dept
CH Annecy Genevois
Institut de Recherche Biomedicale des Armees
Marseille North Hospital, France
Samu of Necker, Paris, France
Samu of Annecy, France
Military Hospital Percy , Clamart, France
Military Hospital Begin, Saint-Mandé, France
Centre de transfusion sanguine des Armées, Clamart, France
Henri Mondor University Hospital
Samu of Beaujon, Clichy-La-Garenne, France
Samu of Lariboisière, Paris, France
Samu of Henri Mondor, Créteil, France
Samu of Brest, Brest , France
Samu of Pau , Pau , France
Information provided by (Responsible Party):
Daniel Jost, Fire Brigade Of Paris Emergency Medicine Dept

Tracking Information
First Submitted Date  ICMJE March 27, 2016
First Posted Date  ICMJE April 13, 2016
Last Update Posted Date January 7, 2020
Study Start Date  ICMJE April 1, 2016
Actual Primary Completion Date October 31, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 7, 2019)
the International Normalized Ratio level (international unit IU) at hospital admission [ Time Frame: 1 day ]
Original Primary Outcome Measures  ICMJE
 (submitted: April 12, 2016)
Prothrombin level change (percentage) [ Time Frame: 1 day ]
The change in the level of Prothrombin (PR), between the PR at hospital admission and the PR originally taken in the pre-hospital period
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: August 7, 2019)
  • number of plasma units administered at 24 and 48 hours [ Time Frame: 48 hours ]
  • Number of RBC Concentrates units administered at 24 and 48 hours [ Time Frame: 48 hours ]
  • Number of platelet concentrates units administered at 24 and 48 hours [ Time Frame: 48 hours ]
  • Total Intensive care unit of stay (days) [ Time Frame: 30 days ]
  • Survival [ Time Frame: 30 days ]
  • FLYP prehospital usability in civilian population (questionnaire) [ Time Frame: 30 days ]
    Compilation of technical and logistical difficulties encountered before, during and after administration of FLYP
  • Fibrinogen level (grams) [ Time Frame: 1 day ]
  • Prothrombin level change (percentage) [ Time Frame: 48 hours ]
    The difference in the level of Prothrombin (PT), between prehospital and hospital admission
  • the level of coagulation factors (international unit IU) at hospital admission [ Time Frame: 1 day ]
  • Quantity of fibrinogen administered in grams at 24 and 48 hours [ Time Frame: 48 hours ]
  • quantity of coagulation factors administered (international units IU) [ Time Frame: 48 hours ]
    quantity of coagulation factors administered (international units IU)
  • Thromboelastometry median clotting time (CT) (minutes). [ Time Frame: 1 hour ]
    Time in minutes and secondes for each step coming from rotational elastometry
  • Thromboelastometry median Clot Formation Time (CFT) in minutes and seconds [ Time Frame: 1 hour ]
    Time in minutes and seconds for each step coming from rotational elastometry
  • Thromboelastometry median maximal lysis (ML) time in minutes ans seconds [ Time Frame: 1 hour ]
    Time in minutes and seconds for each step coming from rotational elastometry
  • Thromboelastometry alpha angle (degrees) [ Time Frame: 1 hour ]
    measure unit : degrees
  • Thromboelastometry median Maximal Clot Firmness (MCF) time in minutes and seconds [ Time Frame: 1 hour ]
    Time in minutes and seconds for each step coming from rotational elastometry
Original Secondary Outcome Measures  ICMJE
 (submitted: April 12, 2016)
  • international normalized ratio change (international unit) international normalized ratio level change (international unit IU) [ Time Frame: 1 day ]
    The change in the level of international normalized ratio , between the international normalized ratio at hospital admission and the international normalized ratio originally taken in the pre-hospital period
  • Coagulation factors level change (international unit IU) [ Time Frame: 1 day ]
    The change in the level of coagulation factors, between their level at hospital admission and the level originally taken in the pre-hospital period
  • FLYP prehospital usability in civilian population (questionnaire) [ Time Frame: 30 days ]
    Compilation of technical and logistical difficulties encountered before, during and after administration of FLYP
  • Fibrinogen level variation (grams) [ Time Frame: 1 day ]
    The change in fibrinogen level in grams
  • Total Intensive care unit of stay (days) [ Time Frame: 30 days ]
    Number of days
  • Survival [ Time Frame: 30 days ]
    Number of days
  • Thromboelastometry median clotting time (CT) (minutes). [ Time Frame: 1 hour ]
    Time in minutes and secondes for each step coming from rotational elastometry
  • Thromboelastometry median Clot Formation Time (CFT) in minutes and seconds [ Time Frame: 1 hour ]
    Time in minutes and seconds for each step coming from rotational elastometry
  • Thromboelastometry median Maximal Clot Firmness (MCF) time in minutes and seconds [ Time Frame: 1 hour ]
    Time in minutes and seconds for each step coming from rotational elastometry
  • Thromboelastometry median maximal lysis (ML) time in minutes ans seconds [ Time Frame: 1 hour ]
    Time in minutes and seconds for each step coming from rotational elastometry
  • Thromboelastometry alpha angle (degrees) [ Time Frame: 1 hour ]
    measure unit : degrees
  • Number of RBC Concentrates units administered [ Time Frame: 6 hours ]
    quantity of administration of RBC concentrates
  • Number of RBC Concentrates units administered [ Time Frame: 12 hours ]
    quantity of administration of RBC concentrates
  • Number of RBC Concentrates units administered [ Time Frame: 24 hours ]
    quantity of administration of RBC concentrates
  • Number of RBC Concentrates units administered [ Time Frame: 48 hours ]
    quantity of administration of RBC concentrates administered
  • Number of platelet concentrates units administered [ Time Frame: 6 hours ]
    quantity of administration of platelet concentrates administered
  • Number of platelet concentrates units administered [ Time Frame: 12 hours ]
    quantity of administration of platelet concentrates administered
  • Number of platelet concentrates units administered [ Time Frame: 24 hours ]
    quantity of administration of platelet concentrates administered
  • Number of platelet concentrates units administered [ Time Frame: 48 hours ]
    quantity of administration of platelet concentrates administered
  • Quantity of fibrinogen administered in grams [ Time Frame: 6 hours ]
    quantity of fibrinogen administered in grams
  • Quantity of fibrinogen administered in grams [ Time Frame: 12 hours ]
    quantity of administration of fibrinogen in grams
  • Quantity of fibrinogen administered in grams [ Time Frame: 24 hours ]
    quantity of administration of fibrinogen in grams
  • Quantity of fibrinogen administered in grams [ Time Frame: 48 hours ]
    quantity of administration of fibrinogen in grams
  • quantity of coagulation factors administered (international units IU) [ Time Frame: 6 hours ]
    quantity of coagulation factors administered (international units IU)
  • quantity of coagulation factors administered (international units IU) [ Time Frame: 12 hours ]
    quantity of coagulation factors administered (international units UI)
  • quantity of coagulation factors administered (international units IU) [ Time Frame: 24 hours ]
    quantity of coagulation factors administered (international units IU)
  • quantity of coagulation factors administered (international units IU) [ Time Frame: 48 hours ]
    quantity of coagulation factors administered (international units IU)
  • number of plasma units administered [ Time Frame: 6 hours ]
    number of plasma units administered
  • number of plasma units administered [ Time Frame: 12 hours ]
    number of plasma units administered
  • number of plasma units administered [ Time Frame: 24 hours ]
    number of plasma units administered
  • number of plasma units administered [ Time Frame: 48 hours ]
    number of plasma units administered
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Pre-hospital Administration of Lyophilized Plasma for Post-traumatic Coagulopathy Treatment (PREHO-PLYO)
Official Title  ICMJE Interest of Pre-hospital Administration of Lyophilized Plasma to Prevent or Treat Coagulopathy Associated With Post-traumatic Hemorrhagic Shock (PREHO-PLYO Study )
Brief Summary

In severe bleeding due to trauma, a decrease in coagulation factors maintains and promotes bleeding. The plasma allows, through its contribution of coagulation factors, early prevention or correction of this post-trauma induced coagulopathy. This study aims to measure the effectiveness of pre-hospital FLYP administration in case of traumatic hemorrhagic shock, in the occurrence or the treatment of a post traumatic induced coagulopathy.

Study Design

This is a randomized controlled multicenter open label study in two parallel groups.

Eligibility criteria : adult, victim of a hemorrhagic shock of traumatic origin with [systolic blood pressure <70 mmHg] or Shock Index >1.1 The patients will receive either FLYP either the usual treatment as given in the recommendations for best practice.

The primary endpoint is the International Normalized Ratio (INR) at hospital admission.

The study must confirm the link between causality of early administration of plasma in improving post-traumatic coagulopathy. The study must show safe usage in out-of-hospital situations and the ability of medical staff to meet the requirements of the health authorities in terms of product use as well as in terms of traceability of the victims and the treatment they received.

Detailed Description

In severe bleeding due to trauma, a fall in coagulation factors maintains and promotes bleeding. The plasma allows, through its contribution of coagulation factors, early prevention or correction of this post-traumatic coagulopathy.

This labile blood product has so far only been used in armed conflicts by military medical and surgical units deployed in External Operations (EXOP) to meet the logistical constraints of the operating environment and the need to have, without delay, therapeutic plasma to treat bleeding casualties. Unlike frozen plasma used in hospitals, FLYP is stored at room temperature and is reconstituted in less than 6 mins.

In the civilian world, FLYP could be used by health institutions who have major logistical difficulties which do not allow them to ensure a cold chain of sub-zero temperatures, or in extreme emergency situations with the need for an immediate therapeutic plasma supply. In this second indication, FLYP should be used until the fresh frozen plasma is thawed and available. Its use in pre-hospital situations is also justified due to its immediate availability and storage conditions.

FLYP is sterile and is in powder-form with a residual humidity not exceeding 2%. It is packaged in a sterile and pyrogenic glass vial.

The main objective is to measure the effectiveness of pre-hospital FLYP administration in case of traumatic hemorrhagic shock, in the occurrence or the treatment of a post traumatic coagulopathy.

The secondary objectives consist in assessing the following outcomes :

(1) the need for massive transfusion (3) the ICU length of stay (4) the survival rate on day 30 (5) FLYP prehospital usability in civilian population (the compilation of technical and logistical difficulties encountered with administration of FLYP) (6) the Prothrombin time (PT) at hospital admission. Normal values for PT are 70 - 130%.

(7) the fibrinogen level at hospital admission (8) the variation in the level of PT, between the pre-hospital setting and the hospital admission .

(9) the variation in the level of INR, between the pre-hospital setting and the hospital admission .

(10) the variation in the fibrinogen level between the pre-hospital setting and the hospital admission .

Method

The attribution of the experimental treatment (FLYP or saline), to each patient who will receive a treatment numbered from 1 to 140, was carried out in advance using STATA 14.0 software.

Type of randomisation : randomisation in blocks of 2, stratified by center.

Treatments are allocated to participants in each "pre-hospital" center by ascending number.

Participants and investigators are therefore not blinded to the allocated treatment.However, the statistical analysis is planned to be carried out as a blind study regarding knowledge of the allocated treatment.

The planned experimental design is identical for each pre-hospital investigation centre.

Care of a patient in traumatic hemorrhagic shock is identical from one investigating centre to another: it is based on formalized expert recommendations on hemorrhagic shock resuscitation.

Determination of the number of subjects required

Coagulation factors were measured in a pre-after study in 2010 in the army in severely traumatized patients. The "before" period consisted of an isotonic infusion of saline saline chlorine, the "after" period of FLYP transfusion. In total, the inclusion of 124 patients showed a significant difference between the two groups in terms of PT value. In the absence of any other data available at the time of writing the protocol, we have brought the number of subjects required to 140 (= 2X 70) according to a 10% in the follow-up.

There is no planned interim analysis.

The administration of the treatment in the study is stopped if any adverse event (AE) occurs (abnormal clinical manifestation,...) and the offending experimental treatment is retained. Usual care and corrective actions are continued in the field, during transport and at the receiving hospital. An independent oversight committee meeting is organized to discuss the stopping or the continuation of the study according to the nature of the AE.

Comparability of the 2 groups for the primary endpoint:

The median INR values are compared between the two groups, after adjustment on other variables if necessary.

Comparability of the 2 groups for the secondary endpoints:

  • Transfusion requirement will be judged by the number of units transfused after arrival at the hospital: packed red blood cells (RBC), platelet concentrates, fibrinogen, coagulation factors and plasma. The transfusion requirement will be measured over a period of 24 to 48 hours.
  • The median number of days in the ICU between the two groups will use the medians test
  • Survival analysis up to 30 days will be based on the comparison of Kaplan-Meier curves, by the log-rank test, and a Cox model to estimate the role of administration of FLYP on survival, taking into account potential confounding factors.
  • The usability of administering FLYP will be judged on the grounds of interruption or non-administration of the experimental treatment, depending on the ability to respect the procedure and the use of a Labile Blood Product according to the rules of good practice.
  • The average differential (pre-hospital -hospital) of coagulation parameters between the two groups will be compared by an ANCOVA adjusted on other variables if needed.

INTERRUPTION OR STOPPING OF THE STUDY

The sponsor has the responsibility to report, to the national health authority , any serious and unexpected adverse events attributable to the labile blood product of cell therapy and/or protocol within 15 days (7 days in case of death and life-threatening situations).

In the case of occurrence of an incident, accident, or event, interruption of the study is planned after analysis and decision by the hemovigilance and safety committee of the study.

RISKS

A full report on the risks, the description of incidents, accidents and adverse events will be the subject of a chapter in the results section and also in the discussion.

FINANCING

Funding for the study is provided by the Health Department of the Army (promoter, following the acceptance of the study in the context of Clinical research projects in the Health service of armies).

DISCUSSION

The study must confirm the link between causality of early administration of plasma in improving post-traumatic coagulopathy.

The study must show safe usage in out-of-hospital situations and the ability of medical staff to meet the requirements of the health authorities in terms of product use as well as in terms of traceability of the victims and the treatment they received.

CONCLUSION

This is the first study that aims to assess the usability and efficiency of FLYP in prehospital situation.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Shock Hemorrhagic
Intervention  ICMJE
  • Biological: French Lyophilized Plasma

    During the pre-hospital phase, the main events related to this arm are

    • Blood samples taken before treatment (TP, fibrinogen, platelets, RBC, grouping)
    • Usual pre-hospital care according to recommendations in best practices
    • Administration of FLYP
  • Biological: Normale Saline Solution

    During the pre-hospital phase, the main events related to this arm are

    • Blood samples taken before treatment (TP, fibrinogen, platelets, RBC, grouping)
    • Usual pre-hospital care according to recommendations in best practices
    • Administration of Normale Saline Solution
Study Arms  ICMJE
  • Experimental: French Lyophilized Plasma
    receives French Lyophilized Plasma with the usual treatment for post traumatic hemorrhagic shock as given in the recommendations for best practice
    Intervention: Biological: French Lyophilized Plasma
  • Active Comparator: Normal Saline Solution
    receives Normale Saline Solution with the usual treatment of post traumatic hemorrhagic shock as given in the recommendations for best practice
    Intervention: Biological: Normale Saline Solution
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: April 12, 2016)
140
Original Estimated Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE November 30, 2019
Actual Primary Completion Date October 31, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • hemorrhagic shock of traumatic origin
  • [Systolic Blood Pressure <70 mmHg] OR [Shock index > 1.1]

Exclusion Criteria:

  • Refusal to participate in the research
  • Unaffiliated to a social welfare system
  • Age under 18 years
  • Privation of person's liberty
  • Person subject to a safeguard measure of justice
  • Pregnancy
  • Allergy known to Amotosalen® and psoralen
  • Contribution factor clotting other than Plyo
  • Patient initialy in cardiac arrest
  • Patient initially in cardiac arrest, followed by resumption of spontaneous circulation
  • People who could not have blood sample (required for the primary endpoint)
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE France
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02736812
Other Study ID Numbers  ICMJE 2014RC04
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Daniel Jost, Fire Brigade Of Paris Emergency Medicine Dept
Study Sponsor  ICMJE French Defence Health Service
Collaborators  ICMJE
  • Bataillon des marins pompiers de Marseille, France
  • Military Hospital Laveran,Marseille, France
  • Samu of Marseille, France
  • Samu of Lyon, France
  • Lyon-South Hospital, France
  • Hôpital Edouard Herriot
  • Fire Brigade Of Paris Emergency Medicine Dept
  • CH Annecy Genevois
  • Institut de Recherche Biomedicale des Armees
  • Marseille North Hospital, France
  • Samu of Necker, Paris, France
  • Samu of Annecy, France
  • Military Hospital Percy , Clamart, France
  • Military Hospital Begin, Saint-Mandé, France
  • Centre de transfusion sanguine des Armées, Clamart, France
  • Henri Mondor University Hospital
  • Samu of Beaujon, Clichy-La-Garenne, France
  • Samu of Lariboisière, Paris, France
  • Samu of Henri Mondor, Créteil, France
  • Samu of Brest, Brest , France
  • Samu of Pau , Pau , France
Investigators  ICMJE
Study Chair: Jean-Pierre TOURTIER, Professor Fire Brigade Of Paris Emergency Medicine Dept
Principal Investigator: Daniel JOST, MD Fire Brigade Of Paris Emergency Medicine Dept
Study Chair: Anne SAILLIOL, Professor Centre de Transfusion Sanguine des Armées
Study Chair: Catherine VERRET, MD Institut de recherche biomedicale des armées
PRS Account French Defence Health Service
Verification Date January 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP