A Pre-market, Multi-center, International, Double-blind, Randomized, Two-arms, Controlled, Prospective Clinical Investigation Assessing the Safety and Performance of a Medical Device (ClearPlasma™) for the Treatment of Patients Undergoing Coronary Artery Bypass or Valve Replacement

Bleeding Clinical Trial

Official title:

A Pre-market, Multi-center, International, Double-blind, Randomized, Two-arms, Controlled, Prospective Clinical Investigation Assessing the Safety and Performance of a Medical Device (ClearPlasma™) for the Treatment of Patients Undergoing Coronary Artery Bypass or Valve Replacement

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05542277
• Other study ID #: PLAS-01-2021
• Status: Recruiting
• Phase: N/A
• Start date: November 8, 2022
• Est. completion date: June 20, 2024

Study information

• Verified date: December 2023
• Source: PlasFree Ltd.
• Contact: Zeev Dvashi, Ph.D
• Phone: +972-4-6098615
• Email: zeev[@]plas-free.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Bleeding is a significant complication in cardiac surgery, with 10-15% of open cardiac surgery patients experiencing major intra- or post-operative bleeding. To address this unmet need, PLAS-FREE 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 bleeding in patients undergoing plasma transfusions.

Description:

Bleeding is a significant complication in cardiac surgery, with 10-15% of open cardiac surgery patients experiencing major intra- or post-operative bleeding. Bleeding complications are associated with worse clinical outcomes, including a higher risk of infection, ischemic events attributable to hypo-perfusion (e.g., myocardial infarction, acute kidney injury), in-hospital mortality, and transfusion-related adverse events. Additionally, bleeding complications are an important driver of blood product utilization in cardiac surgery. Coagulopathy and bleeding after cardiac surgery are often a multifactorial problem, thus there is unmet need to find new technologies that can give better care to these bleeding patients. In 2016, it was estimated that one million people throughout the world undergo cardiac surgery each year. Most of these surgeries are Coronary artery bypass grafting and valves replacement. Coronary artery bypass grafting (CABG) is still the most commonly performed cardiac surgery procedure worldwide, representing annual volumes of approximately 200,000 isolated cases in the US and an average incidence rate of 62 per 100,000 inhabitants in western European countries. Aortic valve replacement is procedure that treat diseases affecting the aortic valve, one of four valves that control blood flow through the heart. In the United States, it is estimated that 2.5% of the general population, 8.5% of those 65-74 years of age and 13.2% of those ≥75 years of age have moderate to severe valvular diseases. These surgeries are commonly done in the western countries, however, the ability to halt the bleed remain challenge for most clinicians. Failed or delayed treatment of a massive bleeding can result in irreversible end-organ damage (e.g., renal failure), cardiovascular events (e.g., stroke, myocardial injury) or death, accompanied by significantly increased costs.

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.

PLAS-FREE 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 bleeding in patients undergoing plasma transfusions.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 250
• Est. completion date: June 20, 2024
• Est. primary completion date: January 20, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Patients aged = 18 years

2. Patients undergoing isolated coronary artery bypass grafting or valve replacement surgeries with a cardiopulmonary bypass

3. Patients that need at least 2 units of plasma transfusion according to the physician's decision.

4. Patients understanding the nature of the study and providing their informed consent to participation;

5. Patients willing and able to attend the follow-up visits and procedures foreseen by study protocol.

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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. Patients who are hemodynamically unstable and required pressor administration at the time of enrolment (i.e. hypovolemic shock, cardiogenic shock);

4. Transfusion of cryoprecipitate during procedure.

5. Patients suffering from Hemophilia A or B;

6. Patients suffering from venous and arterial thromboembolic events within 3 months before the enrolment;

7. Patients with increased risk of blood clotting, according to Investigator's judgement;

8. Patients with fluid accumulation in the brain at the time of enrolment.

9. Patients with retinal thrombosis at the time of enrolment;

10. Patients with history of allergic reaction to plasma, polyethersyplone or polycarbonate;

11. Patients suffering from known IgA deficiency at the time of enrolment;

12. 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;

13. Patients who are participating or have participated in other clinical studies within the 30 days before the study enrolment.

14. 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;

15. Female Patients of childbearing age (less than 12 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.

Related Conditions & MeSH terms

• Bleeding
• Bypass Complication
• Valve Replacement

Intervention

Device:
• ClearPlasma
ClearPlasma ClearPlasma™ is an extra-corporeal plasma filtration device, 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

Locations

Country	Name	City	State
Czechia	Charles University Teaching Hospital	Hradec Králové
Czechia	University Hospital Olomouc	Olomouc
Czechia	University Hospital Ostrava	Ostrava
Israel	Wolfson Medical center	Holon
Israel	Rabin Medical Center - Beilinson	Petah Tikva
Israel	Sheba Medical Center	Ramat Gan
Poland	Szpital Kliniczny im. Heliodora Swiecickiego Uniwersytetu Medycznego w Poznaniu	Poznan
Poland	Narodowy Instytut Kardiologii Stefana kardynala Wyszynskiego Panstwowy Instytut Badawczy	Warszawa

Sponsors (1)

Lead Sponsor	Collaborator
PlasFree Ltd.

Countries where clinical trial is conducted

Czechia,  Israel,  Poland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	ClearPlasma efficacy	Post-operative blood loss (mL) within 24 hours after surgery, defined as total output of mediastinal and pleural chest tubes. [time frame: up to 24 hours after procedure]	30 days
Secondary	Transfusion- related SAE	Comparison of the number of transfusion- related SAEs between the groups. [time frame: discharge]obtained through filtration with ClearPlasma™ in patients after coronary artery bypass grafting or valve replacement surgery and to compare it to the same procedure carried out using FFP units.	30 days
Secondary	Hemoglobin levels	Comparison of hemoglobin levels drop between the groups [time frame: measured at patient's departure from the operating room/admitting to the ICU and compared to the lowest hemoglobin value until discharge]	30 days
Secondary	Post-operative blood loss	Post-operative blood loss (mL) within 12 hours after surgery, defined as total output of mediastinal and pleural chest tubes. [time frame: up to 12 hours after procedure]	30 days
Secondary	Total blood loss	Total blood loss, defined as total output of chest tubes from insertion till removal [time frame: drain removal]	30 days
Secondary	ClearPlasma	Ratio of bleeding events between the groups [time frame: discharge]	30 days
Secondary	bleeding events-	Ratio of bleeding events requiring re-intervention up to discharge [time frame: discharge]	30 days
Secondary	major bleeding	Ratio of major bleeding defined as blood loss greater than >1000 mL in first 12 h and/or need for surgical revision owing to bleeding; [time frame: discharge]	30 days
Secondary	Mortality	All-cause mortality[time frame: 30 days]	30 days
Secondary	In- hospital mortality	In- hospital mortality [time frame: discharge]	30 days
Secondary	Number of blood units transfused	The number of units of allogeneic blood products transfused until discharge [time frame: discharge]: Red blood cells (RBC) units transfused; Plasma (PDP/FFP) units transfused; Platelet concentrates units transfused	30 days
Secondary	Length of stay in the ICU	Length of stay in the ICU [Time Frame: discharge]	30 days
Secondary	Hospitalization Duration	Total length of hospitalization [Time Frame: discharge]	30 days
Secondary	Incidence of ischemic outcomes	Comparison of the incidence of ischemic outcomes defined as a composite of stroke, transient ischemic attack, acute myocardial infarction, PE and/or acute renal failure [time frame: discharge] Study Groups	30 days