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Trial record 1 of 1 for:    clearplasma
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Clinical Investigation of Safety and Performance of a Medical Device (ClearPlasma) for the Treatment of Patients With Acute Upper Gastrointestinal Hemorrhage.

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ClinicalTrials.gov Identifier: NCT04174989
Recruitment Status : Not yet recruiting
First Posted : November 22, 2019
Last Update Posted : November 22, 2019
Sponsor:
Collaborator:
Sintesi Research Srl
Information provided by (Responsible Party):
PlasFree Ltd.

Brief Summary:

Pre-market, multi-center, international, double-blind, randomized, controlled, prospective, first-in-human clinical investigation of a Class IIb Investigational Medical Device, in which Patients presenting with acute upper gastrointestinal hemorrhage (AUGIH) and due to undergo a plasma transfusion, will be randomized to receive a one-time infusion (up to 8 hours) of up to two 250 mL units of plasminogen-depleted plasma (PDP) or fresh-frozen plasma (FFP).

In case of transfusions needing more than two units, the third unit and above will consist in regular plasma for both treatment groups. Patients will be continuously monitored for 8 hours following the transfusion, and will be assessed between 8-12 hours after plasma transfusion or the following morning (the earlier of the two options), between 24-48 hours after plasma transfusion or at discharge (the earlier of the two options) and after 30+/-3 days after transfusion.


Condition or disease Intervention/treatment Phase
Acute Upper Gastrointestinal Hemorrhage Acute Upper Gastrointestinal Bleeding Other: Plasma treated with ClearPlasma (Extra-corporeal plasma filtration device) Other: Regular fresh-frozen plasma (not treated) Not Applicable

Detailed Description:

Upper gastrointestinal hemorrhage (UGIH) is one of the most common gastrointestinal emergencies, and is associated with significant morbidity and mortality. Acute upper gastrointestinal hemorrhage (AUGIH) management guidelines call for aggressive hemodynamic resuscitation, prevention and treatment of complications and treatment of bleeding, which generally includes endoscopic intervention and transfusion of appropriate blood components. However, in many cases, spontaneous hyperfibrinolysis occurs, jeopardizing pharmacological control of AUGIH. Antifibrinolytic drugs are considered effective in counteracting hyperfibrinolysis, but are associated with various side effects, such as neurotoxicity and accelerated fibrinolysis upon prolonged use.

Fibrin clot breakdown is actively mediated by plasmin, a serine protease which cleaves fibrin. Administration of plasma depleted of plasminogen, the precursor of plasmin, may shift the balance towards coagulation.

PlasFree Ltd. has developed ClearPlasma, a single-use, extracorporeal plasma filtration device which extracts plasminogen from plasma to reduce fibrinolysis. The resulting plasminogen-depleted plasma (PDP) is expected to reduce risk of fibrinolysis and re-bleeding in Patients undergoing plasma transfusions.

The Primary Objective of this trial is to assess the safety profile of a one-time infusion of up to two units of PDP obtained through filtration with ClearPlasma in Patients presenting with acute upper gastrointestinal hemorrhage and to compare it to the same procedure carried out using FFP units.

The Secondary Objective of this trial is to assess the efficacy of a one-time infusion of up to two units of PDP obtained through filtration with ClearPlasma in the reduction of re-bleeding in Patients presenting with acute upper gastrointestinal hemorrhage (as a measure of the performance of ClearPlasma) and to compare it to the same procedure carried out using FFP units.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 50 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: This is a double-blind, multi-center clinical trial. Patients enrolled will be randomized in a 1:1 ratio to receive Plasminogen-Depleted Plasma - PDP (Group A) or Fresh-Frozen Plasma - FFP (Group B).
Masking: Double (Participant, Investigator)
Masking Description: An unblinded sub-Investigator will prepare the plasma bags to be used for treatment (PDP or FFP). The randomization will be carried out in accordance to the the instructions provided, keeping the Investigator's and Patient's blindness about the content of plasma bags used for transfusion of participants.
Primary Purpose: Treatment
Official Title: A Pre-market, Multi-center, International, Double-blind, Randomized, Two-arms, Controlled, Prospective Clinical Investigation Assessing the Safety and Performance of a Class IIb Medical Device (ClearPlasma) for the Treatment of Patients With Acute Upper Gastrointestinal Hemorrhage.
Estimated Study Start Date : December 15, 2019
Estimated Primary Completion Date : June 15, 2020
Estimated Study Completion Date : June 15, 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Plasminogen-Depleted Plasma Infusion
Patients presenting with acute upper gastrointestinal hemorrhage (AUGIH) and due to undergo a plasma transfusion, will be randomized to receive a one-time infusion (up to 8 hours) of up to two 250 mL units of PDP. In case of transfusions needing more than two units, the third unit and above will consist in regular plasma regardless of treatment group. Patients will be continuously monitored for 8 hours following the transfusion, and will be assessed between 8-12 hours after plasma transfusion or the following morning (the earlier of the two options), between 24-48 hours after plasma transfusion or at discharge (the earlier of the two options) and after 30±3 days after transfusion.
Other: Plasma treated with ClearPlasma (Extra-corporeal plasma filtration device)
ClearPlasma is designed to specifically extract plasminogen, a protein that drives fibrinolysis, from up to 250 mL of plasma. ClearPlasma is a non-pyrogenic, sterile, single-use medical device that is indicated for use in conditions where massive bleeding situations exist.

Fresh-Frozen Plasma Infusion
Patients presenting with acute upper gastrointestinal hemorrhage (AUGIH) and due to undergo a plasma transfusion, will be randomized to receive a one-time infusion (up to 8 hours) of up to two 250 mL units of FFP. In case of transfusions needing more than two units, the third unit and above will consist in regular plasma regardless of treatment group. Patients will be continuously monitored for 8 hours following the transfusion, and will be assessed between 8-12 hours after plasma transfusion or the following morning (the earlier of the two options), between 24-48 hours after plasma transfusion or at discharge (the earlier of the two options) and after 30±3 days after transfusion.
Other: Regular fresh-frozen plasma (not treated)
Regular fresh-frozen plasma (not treated)




Primary Outcome Measures :
  1. Safety Profile in Patients treated with PDP versus FFP. [ Time Frame: Entire Study Period (up to 1 month per patient). ]
    Comparison of adverse events rate during the study period and within 30±3 days after transfusion with PDP (group A) or FFP (group B). All adverse occurrences (serious/non-serious or device-related/non-device related) will be recorded prospectively, categorized and evaluated for causality using defined criteria.


Secondary Outcome Measures :
  1. Incidence of re-bleeding episodes in Patients treated with PDP versus FFP. [ Time Frame: Entire Study Period (up to 1 month per patient). ]
    Comparison of the number of re-bleeding episodes occurring for the Patient throughout the study period and within 30±3 days after transfusion with PDP (group A) or FFP (group B).

  2. Duration of hospital stay in Patients treated with PDP versus FFP. [ Time Frame: Entire Study Period (up to 1 month per patient) or until patient discharge. ]
    Comparison of the duration of the hospital stay for the Patient up to 30±3 days after transfusion with PDP (group A) or FFP (group B).

  3. CBC profile in Patients treated with PDP versus FFP. [ Time Frame: Entire Study Period (up to 1 month per patient). ]
    Comparison of complete blood count (CBC) profiles between Patients who received transfusion with PDP (group A) or FFP (group B) at baseline (Screening Visit) versus T=8-12h, T=24-48h and End of Study Visit.

  4. D-dimer profile in Patients treated with PDP versus FFP. [ Time Frame: Entire Study Period (up to 1 month per patient). ]
    Comparison of D-dimer profiles between Patients who received transfusion with PDP (group A) or FFP (group B) at baseline (Screening Visit) versus T=8-12h, T=24-48h and End of Study Visit.

  5. PT/INR (blood coagulation parameter) measurement in Patients treated with PDP versus FFP. [ Time Frame: Entire Study Period (up to 1 month per patient) or until patient discharge. ]
    Comparison of Prothrombin Time and International Normalized Ratio (PT/INR) between Patients who received transfusion with PDP (group A) or FFP (group B) until Patient discharge from hospital.

  6. aPTT (blood coagulation parameter) measurement in Patients treated with PDP versus FFP. [ Time Frame: Entire Study Period (up to 1 month per patient) or until patient discharge. ]
    Comparison of Activated Partial Thromboplastin Time (aPTT) between Patients who received transfusion with PDP (group A) or FFP (group B) until Patient discharge from hospital.

  7. Incidence of venous and arterial thromboembolic events in Patients treated with PDP versus FFP. [ Time Frame: Entire Study Period (up to 1 month per patient). ]
    Comparison of the incidence of venous and arterial thromboembolic events during the study period and within 30±3 days after transfusion with PDP (group A) or FFP (group B).

  8. Plasma transfusion-related mortality in Patients treated with PDP versus FFP. [ Time Frame: Entire Study Period (up to 1 month per patient). ]
    Comparison of the plasma transfusion-related mortality during the study period and within 30±3 days after transfusion with PDP (group A) or FFP (group B).

  9. Total blood loss from transfusion in Patients treated with PDP versus FFP. [ Time Frame: Entire Study Period (up to 1 month per patient) or until patient discharge. ]

    Comparison of total blood loss from transfusion with PDP (group A) or FFP (group B) until Patient discharge from hospital, as measured by:

    1. Red blood cells (RBC) units transfused;
    2. Plasma units transfused;
    3. Platelet units transfused;
    4. Hemoglobin levels.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Male or female Patients.
  2. Patients aged ≥ 18 and ≤ 80 years old.
  3. Patients presenting with acute upper gastrointestinal hemorrhage (> 0.5 L), diagnosed by presence of blood in gastric lavage, hematemesis or melena within no longer than 24 h before enrolment.
  4. Patients presenting with acute upper gastrointestinal hemorrhage (< 24 h) for which fresh frozen plasma (FFP) has been ordered.
  5. Patients understanding the nature of the study and providing their informed consent to participation.
  6. Patients willing and able to attend the follow-up visits and procedures foreseen by study protocol.

Exclusion Criteria:

  1. Patients who underwent a plasma infusion in the 30 days before enrolment.
  2. Patients in a life-threatening condition at the time of enrolment.
  3. Patient on anticoagulant therapy at the time of enrolment.
  4. Patients with known renal failure (creatinine clearance < 30 mL/min) at the time of enrolment.
  5. Patients suffering of Hemophilia A or B.
  6. Patients suffering of venous and arterial thromboembolic events within 3 months before the enrolment.
  7. Patients with history of allergic reaction to plasma, polyethersyplone or polycarbonate.
  8. Patients suffering of IgA deficiency at the time of enrolment.
  9. Patients with history of hemorrhage while on anticoagulant treatment (warfarin, apixaban, rivaroxaban, dabigatran, low molecular weight heparin).
  10. Patients identified by the Investigator to have any underlying medical conditions that may preclude conduct of study procedure (i.e. making the administration of study treatment hazardous) or obscure the interpretation of safety objectives.
  11. Patients who are participating or have participated in other clinical studies within the 30 days before the study enrolment.
  12. Women who are pregnant or breast-feeding or who wish to become pregnant during the period of the clinical investigation and for 3 months later.
  13. Female Patients of childbearing age (less than 24 months after the last menstrual cycle) who do not use adequate contraception *.

    • Methods at low risk of contraceptive failure (less than 1% per year) when used consistently, including: combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal, transdermal), progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable, implantable), some intra-uterine devices.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04174989


Contacts
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Contact: Zeev Dvashi +972-46098615 zeev@plas-free.com

Locations
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Israel
Department of Surgery, Rabin Medical Center
Petah Tikva, Israel, 49100
Contact: Nir Wasserberg, MD    +972-039376202    nirw@clalit.org.il   
Contact: Galia Spectre, MD    +972-039377912    galiasp1@clalit.org.il   
Sub-Investigator: Vered Yahalom, MD         
Italy
S.C. di Anestesia e Rianimazione 1, Azienda Ospedaliera Universitaria Policlinico di Modena
Modena, Italy, 41124
Contact: Massimo Girardis, MD    +39-0594222862    massimo.girardis@unimore.it   
Area Medicina D'Urgenza e Pronto Soccorso, Fondazione Policlinico Universitario A. Gemelli
Roma, Italy, 00168
Contact: Francesco Franceschi, MD    +39-0630157014    francesco.franceschi@unicatt.it   
Contact: Marcello Candelli, MD    +39-0630153161    mcandelli@gmail.com   
Sponsors and Collaborators
PlasFree Ltd.
Sintesi Research Srl
Investigators
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Principal Investigator: Nir Wasserberg, MD Department of Surgery, Rabin Medical Center - Petah Tikva (Israel)

Additional Information:
Publications:

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Responsible Party: PlasFree Ltd.
ClinicalTrials.gov Identifier: NCT04174989    
Other Study ID Numbers: PLAS-01-2019
First Posted: November 22, 2019    Key Record Dates
Last Update Posted: November 22, 2019
Last Verified: November 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by PlasFree Ltd.:
Acute Upper Gastrointestinal Hemorrhage
Gastrointestinal Hemorrhage
Gastrointestinal Bleeding
Acute Upper Gastrointestinal Bleeding
Plasminogen-Depleted Plasma
Plasma Transfusion
Additional relevant MeSH terms:
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Gastrointestinal Hemorrhage
Hemorrhage
Pathologic Processes
Gastrointestinal Diseases
Digestive System Diseases
Plasminogen
Fibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action