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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.

Primary Purpose

Acute Upper Gastrointestinal Hemorrhage, Acute Upper Gastrointestinal Bleeding

Status

Completed

Phase

Not Applicable

Locations

International

Study Type

Interventional

Intervention

Plasma treated with ClearPlasma (Extra-corporeal plasma filtration device)

Regular fresh-frozen plasma (not treated)

About this trial

This is an interventional treatment trial for Acute Upper Gastrointestinal Hemorrhage focused on measuring Acute Upper Gastrointestinal Hemorrhage, Gastrointestinal Hemorrhage, Gastrointestinal Bleeding, Acute Upper Gastrointestinal Bleeding, Plasminogen-Depleted Plasma, Plasma Transfusion

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Male or female Patients.
Patients aged ≥ 18 and ≤ 80 years old.
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.
Patients presenting with acute upper gastrointestinal hemorrhage (< 24 h) for which fresh frozen plasma (FFP) has been ordered.
Patients understanding the nature of the study and providing their informed consent to participation.
Patients willing and able to attend the follow-up visits and procedures foreseen by study protocol.

Exclusion Criteria:

Patients who underwent a plasma infusion in the 30 days before enrolment.
Patients in a life-threatening condition at the time of enrolment.
Patient on anticoagulant therapy at the time of enrolment.
Patients with known renal failure (creatinine clearance < 30 mL/min) at the time of enrolment.
Patients suffering of Hemophilia A or B.
Patients suffering of venous and arterial thromboembolic events within 3 months before the enrolment.
Patients with history of allergic reaction to plasma, polyethersyplone or polycarbonate.
Patients suffering of IgA deficiency at the time of enrolment.
Patients with history of hemorrhage while on anticoagulant treatment (warfarin, apixaban, rivaroxaban, dabigatran, low molecular weight heparin).
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.
Patients who are participating or have participated in other clinical studies within the 30 days before the study enrolment.
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.
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.

Sites / Locations

Charles University Teaching Hospital
University Hospital in Olomouc
University Hospital Ostrava
Wolfson Medical center
Department of Surgery B, Meir Medical Center Kfar Saba
Department of Surgery, Rabin Medical Center
S.C. di Anestesia e Rianimazione 1, Azienda Ospedaliera Universitaria Policlinico di Modena
Area Medicina D'Urgenza e Pronto Soccorso, Fondazione Policlinico Universitario A. Gemelli

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Other

Arm Label

Plasminogen-Depleted Plasma Infusion

Fresh-Frozen Plasma Infusion

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

Safety Profile in Patients treated with PDP versus FFP.

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

Incidence of re-bleeding episodes in Patients treated with PDP versus FFP.

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).

Duration of hospital stay in Patients treated with PDP versus FFP.

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).

CBC profile in Patients treated with PDP versus FFP.

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.

D-dimer profile in Patients treated with PDP versus FFP.

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.

PT/INR (blood coagulation parameter) measurement in Patients treated with PDP versus FFP.

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.

aPTT (blood coagulation parameter) measurement in Patients treated with PDP versus FFP.

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.

Incidence of venous and arterial thromboembolic events in Patients treated with PDP versus FFP.

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).

Plasma transfusion-related mortality in Patients treated with PDP versus FFP.

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).

Total blood loss from transfusion in Patients treated with PDP versus FFP.

Comparison of total blood loss from transfusion with PDP (group A) or FFP (group B) until Patient discharge from hospital, as measured by: Red blood cells (RBC) units transfused; Plasma units transfused; Platelet units transfused; Hemoglobin levels.

Full Information

NCT ID

NCT04174989

First Posted

November 18, 2019

Last Updated

November 13, 2022

Sponsor

PlasFree Ltd.

Collaborators

KCRI

1. Study Identification

Unique Protocol Identification Number

NCT04174989

Brief Title

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

Official Title

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.

Study Type

Interventional

2. Study Status

Record Verification Date

November 2022

Overall Recruitment Status

Completed

Study Start Date

October 24, 2020 (Actual)

Primary Completion Date

June 30, 2022 (Actual)

Study Completion Date

November 13, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

PlasFree Ltd.

Collaborators

KCRI

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Acute Upper Gastrointestinal Hemorrhage, Acute Upper Gastrointestinal Bleeding

Keywords

Acute Upper Gastrointestinal Hemorrhage, Gastrointestinal Hemorrhage, Gastrointestinal Bleeding, Acute Upper Gastrointestinal Bleeding, Plasminogen-Depleted Plasma, Plasma Transfusion

7. Study Design

Primary Purpose

Treatment

Study Phase

Not Applicable

Interventional Study Model

Parallel Assignment

Model Description

Multi-center, international, double-blind, randomized, controlled, prospective, first-in-human clinical investigation, in which Patients presenting with acute upper gastrointestinal hemorrhage (AUGIH) and required plasma transfusion, will be randomized to receive a one-time infusion (up to 8 hours) of up to two 250 mL units of PDP (group A) or FFP (group B). The administration of Plasma needs to be in line with the clinical practice and doctor decision.

Masking

ParticipantInvestigator

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.

Allocation

Randomized

Enrollment

53 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Plasminogen-Depleted Plasma Infusion

Arm Type

Experimental

Arm Description

Arm Title

Fresh-Frozen Plasma Infusion

Arm Type

Other

Arm Description

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.

Intervention Type

Other

Intervention Name(s)

Plasma treated with ClearPlasma (Extra-corporeal plasma filtration device)

Intervention Description

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.

Intervention Type

Other

Intervention Name(s)

Regular fresh-frozen plasma (not treated)

Intervention Description

Regular fresh-frozen plasma (not treated)

Primary Outcome Measure Information:

Title

Safety Profile in Patients treated with PDP versus FFP.

Description

Time Frame

Entire Study Period (up to 1 month per patient).

Secondary Outcome Measure Information:

Title

Incidence of re-bleeding episodes in Patients treated with PDP versus FFP.

Description

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).

Time Frame

Entire Study Period (up to 1 month per patient).

Title

Duration of hospital stay in Patients treated with PDP versus FFP.

Description

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).

Time Frame

Entire Study Period (up to 1 month per patient) or until patient discharge.

Title

CBC profile in Patients treated with PDP versus FFP.

Description

Time Frame

Entire Study Period (up to 1 month per patient).

Title

D-dimer profile in Patients treated with PDP versus FFP.

Description

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.

Time Frame

Entire Study Period (up to 1 month per patient).

Title

PT/INR (blood coagulation parameter) measurement in Patients treated with PDP versus FFP.

Description

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.

Time Frame

Entire Study Period (up to 1 month per patient) or until patient discharge.

Title

aPTT (blood coagulation parameter) measurement in Patients treated with PDP versus FFP.

Description

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.

Time Frame

Entire Study Period (up to 1 month per patient) or until patient discharge.

Title

Incidence of venous and arterial thromboembolic events in Patients treated with PDP versus FFP.

Description

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).

Time Frame

Entire Study Period (up to 1 month per patient).

Title

Plasma transfusion-related mortality in Patients treated with PDP versus FFP.

Description

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).

Time Frame

Entire Study Period (up to 1 month per patient).

Title

Total blood loss from transfusion in Patients treated with PDP versus FFP.

Description

Time Frame

Entire Study Period (up to 1 month per patient) or until patient discharge.

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Male or female Patients. Patients aged ≥ 18 and ≤ 80 years old. 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. Patients presenting with acute upper gastrointestinal hemorrhage (< 24 h) for which fresh frozen plasma (FFP) has been ordered. Patients understanding the nature of the study and providing their informed consent to participation. Patients willing and able to attend the follow-up visits and procedures foreseen by study protocol. Exclusion Criteria: Patients who underwent a plasma infusion in the 30 days before enrolment. Patients in a life-threatening condition at the time of enrolment. Patient on anticoagulant therapy at the time of enrolment. Patients with known renal failure (creatinine clearance < 30 mL/min) at the time of enrolment. Patients suffering of Hemophilia A or B. Patients suffering of venous and arterial thromboembolic events within 3 months before the enrolment. Patients with history of allergic reaction to plasma, polyethersyplone or polycarbonate. Patients suffering of IgA deficiency at the time of enrolment. Patients with history of hemorrhage while on anticoagulant treatment (warfarin, apixaban, rivaroxaban, dabigatran, low molecular weight heparin). 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. Patients who are participating or have participated in other clinical studies within the 30 days before the study enrolment. 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. 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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Francesco Franceschi, MD

Organizational Affiliation

Chief of Emergency Medicine Fondazione Policlinico Universitario A. Gemelli IRCCS Università Cattolica del Sacro Cuore Largo A. Gemelli

Official's Role

Principal Investigator

Facility Information:

Facility Name

Charles University Teaching Hospital

City

Hradec Králové

ZIP/Postal Code

50005

Country

Czechia

Facility Name

University Hospital in Olomouc

City

Olomouc

ZIP/Postal Code

77900

Country

Czechia

Facility Name

University Hospital Ostrava

City

Ostrava

ZIP/Postal Code

70852

Country

Czechia

Facility Name

Wolfson Medical center

City

Holon

ZIP/Postal Code

5822012

Country

Israel

Facility Name

Department of Surgery B, Meir Medical Center Kfar Saba

City

Kfar Saba

ZIP/Postal Code

4428164

Country

Israel

Facility Name

Department of Surgery, Rabin Medical Center

City

Petah Tikva

ZIP/Postal Code

49100

Country

Israel

Facility Name

S.C. di Anestesia e Rianimazione 1, Azienda Ospedaliera Universitaria Policlinico di Modena

City

Modena

ZIP/Postal Code

41124

Country

Italy

Facility Name

Area Medicina D'Urgenza e Pronto Soccorso, Fondazione Policlinico Universitario A. Gemelli

City

Roma

ZIP/Postal Code

00168

Country

Italy

12. IPD Sharing Statement

Plan to Share IPD

Citations:

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21772701

Citation

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Citation

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Links:

URL

https://www.plas-free.com/

Description

PlasFree Ltd. official website

Learn more about this trial

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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