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

NCT04174989 | Completed

• 1 other identifier: PLAS-01-2019
• Study Type: interventional
• Target: 53
• Locations: 3 countries
• Sites: 8

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.

Conditions

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

Outcome Measures

Primary Outcomes (1)

• 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.

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

Secondary Outcomes (9)

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

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

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

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

• CBC profile in Patients treated with PDP versus FFP.

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

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

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

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

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

Study Arms (2)

Plasminogen-Depleted Plasma Infusion

EXPERIMENTAL

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)

Fresh-Frozen Plasma Infusion

OTHER

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)

Interventions

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

Plasminogen-Depleted Plasma Infusion

Regular fresh-frozen plasma (not treated) OTHER

Regular fresh-frozen plasma (not treated)

Fresh-Frozen Plasma Infusion

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• PlasFree Ltd.: lead
• KCRI: collaborator

Study Sites (8)

Charles University Teaching Hospital

Hradec Králové, 50005, Czechia

Location

University Hospital in Olomouc

Olomouc, 77900, Czechia

Location

University Hospital Ostrava

Ostrava, 70852, Czechia

Location

Wolfson Medical center

Holon, 5822012, Israel

Location

Department of Surgery B, Meir Medical Center Kfar Saba

Kfar Saba, 4428164, Israel

Location

Department of Surgery, Rabin Medical Center

Petah Tikva, 49100, Israel

Location

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

Modena, 41124, Italy

Location

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

Roma, 00168, Italy

Location

Related Publications (10)

• 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.

  PMID: 21772701 BACKGROUND

• 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.

  PMID: 9684804 BACKGROUND

• 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.

  PMID: 23215650 BACKGROUND

• 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.

  PMID: 24369318 BACKGROUND

• 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.

  PMID: 22578374 BACKGROUND

• 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.

  PMID: 7627034 BACKGROUND

• 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.

  PMID: 20419759 BACKGROUND

• 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.

  PMID: 17900274 BACKGROUND

• 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.

  PMID: 20963925 BACKGROUND

• 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.

  PMID: 22534226 BACKGROUND

Related Links

• PlasFree Ltd. official website

MeSH Terms

Conditions

Gastrointestinal Hemorrhage

Condition Hierarchy (Ancestors)

Gastrointestinal Diseases; Digestive System Diseases; Hemorrhage; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Francesco Franceschi, MD

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

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: 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.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: November 18, 2019
• First Posted: November 22, 2019
• Study Start: October 24, 2020
• Primary Completion: June 30, 2022
• Study Completion: November 13, 2022
• Last Updated: November 15, 2022

Record last verified: 2022-11

Data Sharing

• IPD Sharing: Will not share

Locations

CZ (3); IT (2); IL (3)