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

NCT ID: NCT04174989

Last Updated: 2022-11-15

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 53 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-10-24
• Study Completion Date: 2022-11-13

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.

Conditions

Acute Upper Gastrointestinal Hemorrhage; Acute Upper Gastrointestinal Bleeding

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

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.

Group Type: EXPERIMENTAL

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

Intervention Type: OTHER

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.

Group Type: OTHER

Regular fresh-frozen plasma (not treated)

Intervention Type: OTHER

Regular fresh-frozen plasma (not treated)

Interventions

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.

Intervention Type: OTHER

Regular fresh-frozen plasma (not treated)

Regular fresh-frozen plasma (not treated)

Intervention Type: OTHER

Eligibility 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

KCRI

OTHER

Sponsor Role: collaborator

PlasFree Ltd.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Francesco Franceschi, MD

Role: PRINCIPAL_INVESTIGATOR

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

Locations

Charles University Teaching Hospital

Hradec Králové, , Czechia

University Hospital in Olomouc

Olomouc, , Czechia

University Hospital Ostrava

Ostrava, , Czechia

Wolfson Medical center

Holon, , Israel

Department of Surgery B, Meir Medical Center Kfar Saba

Kfar Saba, , Israel

Department of Surgery, Rabin Medical Center

Petah Tikva, , Israel

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

Modena, , Italy

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

Roma, , Italy

Countries

Czechia; Israel; Italy

References

Arya RC, Wander G, Gupta P. Blood component therapy: Which, when and how much. J Anaesthesiol Clin Pharmacol. 2011 Apr;27(2):278-84. doi: 10.4103/0970-9185.81849.

Reference Type: BACKGROUND

PMID: 21772701 (View on PubMed)

Demarmels Biasiutti F, Sulzer I, Stucki B, Wuillemin WA, Furlan M, Lammle B. Is plasminogen deficiency a thrombotic risk factor? A study on 23 thrombophilic patients and their family members. Thromb Haemost. 1998 Jul;80(1):167-70.

Reference Type: BACKGROUND

PMID: 9684804 (View on PubMed)

Hirayama F. Current understanding of allergic transfusion reactions: incidence, pathogenesis, laboratory tests, prevention and treatment. Br J Haematol. 2013 Feb;160(4):434-44. doi: 10.1111/bjh.12150. Epub 2012 Dec 6.

Reference Type: BACKGROUND

PMID: 23215650 (View on PubMed)

Matei D, Groza I, Furnea B, Puie L, Levi C, Chiru A, Cruciat C, Mester G, Vesa SC, Tantau M. Predictors of variceal or nonvariceal source of upper gastrointestinal bleeding. An etiology predictive score established and validated in a tertiary referral center. J Gastrointestin Liver Dis. 2013 Dec;22(4):379-84.

Reference Type: BACKGROUND

PMID: 24369318 (View on PubMed)

Pandey S, Vyas GN. Adverse effects of plasma transfusion. Transfusion. 2012 May;52 Suppl 1(Suppl 1):65S-79S. doi: 10.1111/j.1537-2995.2012.03663.x.

Reference Type: BACKGROUND

PMID: 22578374 (View on PubMed)

Rockall TA, Logan RF, Devlin HB, Northfield TC. Incidence of and mortality from acute upper gastrointestinal haemorrhage in the United Kingdom. Steering Committee and members of the National Audit of Acute Upper Gastrointestinal Haemorrhage. BMJ. 1995 Jul 22;311(6999):222-6. doi: 10.1136/bmj.311.6999.222.

Reference Type: BACKGROUND

PMID: 7627034 (View on PubMed)

Rubinstein LV, Steinberg SM, Kummar S, Kinders R, Parchment RE, Murgo AJ, Tomaszewski JE, Doroshow JH. The statistics of phase 0 trials. Stat Med. 2010 May 10;29(10):1072-6. doi: 10.1002/sim.3840.

Reference Type: BACKGROUND

PMID: 20419759 (View on PubMed)

Schuster V, Hugle B, Tefs K. Plasminogen deficiency. J Thromb Haemost. 2007 Dec;5(12):2315-22. doi: 10.1111/j.1538-7836.2007.02776.x. Epub 2007 Sep 26.

Reference Type: BACKGROUND

PMID: 17900274 (View on PubMed)

Association of Anaesthetists of Great Britain and Ireland; Thomas D, Wee M, Clyburn P, Walker I, Brohi K, Collins P, Doughty H, Isaac J, Mahoney PM, Shewry L. Blood transfusion and the anaesthetist: management of massive haemorrhage. Anaesthesia. 2010 Nov;65(11):1153-61. doi: 10.1111/j.1365-2044.2010.06538.x.

Reference Type: BACKGROUND

PMID: 20963925 (View on PubMed)

Wilkins T, Khan N, Nabh A, Schade RR. Diagnosis and management of upper gastrointestinal bleeding. Am Fam Physician. 2012 Mar 1;85(5):469-76.

Reference Type: BACKGROUND

PMID: 22534226 (View on PubMed)

Related Links

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

PlasFree Ltd. official website

Other Identifiers

PLAS-01-2019

Identifier Type: -

Identifier Source: org_study_id