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

November 13, 2022 updated by: PlasFree Ltd.

MULTI-CENTER,DOUBLE-BLIND, RANDOMIZED, TWO-ARMS, CONTROLLED, PROSPECTIVE CLINICAL INVESTIGATION ASSESSING THE SAFETY AND PERFORMANCE OF A CLASS IIb MEDICAL DEVICE (CLEARPLASMATM) FOR THE TREATMENT OF PATIENTS WITH ACUTE UPPER GASTROINTESTINAL HEMORRHAGE.

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

53

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Czechia
      • Hradec Králové, Czechia, 50005
        • Charles University Teaching Hospital
      • Olomouc, Czechia, 77900
        • University Hospital in Olomouc
      • Ostrava, Czechia, 70852
        • University Hospital Ostrava
  • Israel
      • Holon, Israel, 5822012
        • Wolfson Medical Center
      • Kfar Saba, Israel, 4428164
        • Department of Surgery B, Meir Medical Center Kfar Saba
      • Petah Tikva, Israel, 49100
        • Department of Surgery, Rabin Medical Center
  • Italy
      • Modena, Italy, 41124
        • S.C. di Anestesia e Rianimazione 1, Azienda Ospedaliera Universitaria Policlinico di Modena
      • Roma, Italy, 00168
        • Area Medicina D'Urgenza e Pronto Soccorso, Fondazione Policlinico Universitario A. Gemelli

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

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:

  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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / 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.
Other: 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)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
Entire Study Period (up to 1 month per patient).

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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).
Entire Study Period (up to 1 month per patient).
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).
Entire Study Period (up to 1 month per patient) or until patient discharge.
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.
Entire Study Period (up to 1 month per patient).
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.
Entire Study Period (up to 1 month per patient).
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.
Entire Study Period (up to 1 month per patient) or until patient discharge.
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.
Entire Study Period (up to 1 month per patient) or until patient discharge.
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).
Entire Study Period (up to 1 month per patient).
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).
Entire Study Period (up to 1 month per patient).
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.
Entire Study Period (up to 1 month per patient) or until patient discharge.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

PlasFree Ltd.

Collaborators

KCRI

Investigators

  • Principal Investigator: Francesco Franceschi, MD, Chief of Emergency Medicine Fondazione Policlinico Universitario A. Gemelli IRCCS Università Cattolica del Sacro Cuore Largo A. Gemelli

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

October 24, 2020

Primary Completion (Actual)

June 30, 2022

Study Completion (Actual)

November 13, 2022

Study Registration Dates

First Submitted

November 18, 2019

First Submitted That Met QC Criteria

November 20, 2019

First Posted (Actual)

November 22, 2019

Study Record Updates

Last Update Posted (Actual)

November 15, 2022

Last Update Submitted That Met QC Criteria

November 13, 2022

Last Verified

November 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • PLAS-01-2019

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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