A Study of Intra-thrombus Plasmin (Human) In Acute Peripheral Arterial Occlusion

NCT ID: NCT01222117

Last Updated: 2017-01-16

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 174 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-12-31
• Study Completion Date: 2016-01-31

Brief Summary

The primary purpose of this Phase 2 study is to optimize Plasmin delivery by comparing different delivery regimens in patients with peripheral arterial occlusion. The study includes a blinded plasminogen activator treatment group and a blinded plasminogen activator placebo group. The study will also assess safety and tolerability of Plasmin at 150 and 250 mg doses.

Conditions

Acute Peripheral Arterial Occlusion

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Plasmin Open-label Treatment Group A

Open-label 150 mg Plasmin administered without initial proximal pulse; 5-hour infusion using 10 mL/hour infusion rate.

Group Type: EXPERIMENTAL

Plasmin

Intervention Type: BIOLOGICAL

Plasmin prepared in 0.9% saline for injection

Plasmin Open-label Treatment Group B

Open-label 150 mg Plasmin administered with initial proximal pulse; 5-hour infusion using 15 mL/hour infusion rate

Group Type: EXPERIMENTAL

Plasmin

Intervention Type: BIOLOGICAL

Plasmin prepared in 0.9% saline for injection

Plasmin Open-label Treatment Group C

Open-label 150 mg Plasmin administered with proximal pulse; 5 hour infusion using 30 mL/hour infusion rate.

Group Type: EXPERIMENTAL

Plasmin

Intervention Type: BIOLOGICAL

Plasmin prepared in 0.9% saline for injection

Plasmin Open-label Treatment Group D

Open-label 150 mg Plasmin administered with proximal pulse; 2-hour infusion using 35 mL/hour infusion rate

Group Type: EXPERIMENTAL

Plasmin

Intervention Type: BIOLOGICAL

Plasmin prepared in 0.9% saline for injection

Plasminogen Activator Blinded Group E

PA administered for five hours at a dose and volume according to the Investigator's clinical judgement/standard practice

Group Type: ACTIVE_COMPARATOR

Plasminogen Activator

Intervention Type: BIOLOGICAL

Plasminogen activator used according to the Investigator's clinical judgment.

PA Placebo Blinded Treatment Arm F

PA placebo (normal saline for injection) administered for five hours at a dose and volume according to the Investigator's clinical judgement/standard practice for PA administration

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: OTHER

Normal saline for injection at the same volume as the plasminogen activator.

Plasmin Open-label Treatment Group G

Open-label 150 mg Plasmin administered without pulsing; 5-hour infusion using 60 mL/hour infusion rate

Group Type: EXPERIMENTAL

Plasmin

Intervention Type: BIOLOGICAL

Plasmin prepared in 0.9% saline for injection

Plasmin Open-label Treatment Group H

Open-label 150 mg Plasmin administered without pulsing; 2-hour infusion using 75 mL/hour infusion rate

Group Type: EXPERIMENTAL

Plasmin

Intervention Type: BIOLOGICAL

Plasmin prepared in 0.9% saline for injection

Plasmin Open-label Treatment Group I

Open-label 150 mg Plasmin administered without pulsing; 5-hour infusion using 30 mL/hour infusion rate with balloon occlusion catheter

Group Type: EXPERIMENTAL

Plasmin

Intervention Type: BIOLOGICAL

Plasmin prepared in 0.9% saline for injection

Plasmin Open-label Treatment Group J

Open-label 150 mg Plasmin administered without pulsing; 2-hour infusion using 35 mL/hour infusion rate with balloon occlusion catheter

Group Type: EXPERIMENTAL

Plasmin

Intervention Type: BIOLOGICAL

Plasmin prepared in 0.9% saline for injection

Plasmin Open-label Treatment Group M

Open-label 250 mg Plasmin administered without pulsing; 5-hour infusion using 30 mL/hour infusion rate with balloon occlusion catheter

Group Type: EXPERIMENTAL

Plasmin

Intervention Type: BIOLOGICAL

Plasmin prepared in 0.9% saline for injection

Interventions

Plasmin

Plasmin prepared in 0.9% saline for injection

Intervention Type: BIOLOGICAL

Plasminogen Activator

Plasminogen activator used according to the Investigator's clinical judgment.

Intervention Type: BIOLOGICAL

Placebo

Normal saline for injection at the same volume as the plasminogen activator.

Intervention Type: OTHER

Other Intervention Names

Plasmin (Human); tissue plasminogen activator (tPA); urokinase (UK); Normal saline

Eligibility Criteria

Inclusion Criteria

• Unilateral limb ischemia - Society of Vascular Surgery Categories I and IIa
• Onset of symptoms less than or equal to 14 days
• Thrombosed infrainguinal bypass graft or native artery
• Diagnosis by arteriography of occlusive thrombus in graft or artery
• Ability to embed the infusion catheter into the thrombus
• Women of childbearing potential must use contraception and have a negative pregnancy test

Exclusion Criteria

• Any medical or social condition that may interfere with study participation
• Women who are pregnant or lactating
• Hemorrhagic stroke history
• Thrombotic or embolic stroke or cerebrovascular events (including transient ischemic attack) within one year
• Intracranial or spinal neurosurgery, or severe intracranial trauma in the last 3 months
• Major surgery, organ biopsy, or major trauma within the past 10 days
• Lumbar puncture or non-compressible arterial puncture in the past 10 days
• Intraocular surgery within the past 10 days
• Active gastrointestinal or organ bleeding
• Uncontrolled arterial hypertension (systolic blood pressure >180 mmHg or diastolic blood pressure >110 mmHg)
• Known intracranial neoplasm, aneurysm, or arteriovenous malformation
• Current bleeding diathesis
• Platelet count <75 x 10e9/L
• Active graft infection
• Occlusion occurred within one month of synthetic graft placement
• Occlusion occurred within 6 months of autologous graft placement
• A sequential composite graft with dual outflows to correct multiple occlusions
• Medically unable to tolerate an open vascular procedure
• Known prothrombotic state
• Hemoglobin <10.0 g/dL
• Impaired renal function or renal disease that constitutes a contraindication to contrast angiography, including creatinine >2.0 mg/dL
• Treatment with a full dose plasminogen activator (PA) within the last 48 hours
• Treatment with a glycoprotein IIb/IIIa class of platelet inhibitor within the past 5 days
• Treatment with oral anticoagulants, and with an international normalized ratio of >1.7

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

Sponsors

Grifols Therapeutics LLC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Kecia Courtney

Role: STUDY_DIRECTOR

Grifols Therapeutics

Locations

Kaleida Health System

Buffalo, New York, United States

Cleveland Clinic

Cleveland, Ohio, United States

Ziekenhuis Oost Limburg, Campus St. Jan

Genk, Limburg, Belgium

Erasme Hospital, Brussels

Brussels, , Belgium

University Hospital Antwerp

Edegem, , Belgium

Chirurgie UZ Leuven

Leuven, , Belgium

Clinic of Vascular Surgery and Angiology

Sofia, , Bulgaria

Tokuda Hospital Sofia

Sofia, , Bulgaria

Vascular Centre Vitkovicka Nemocnice

Ostrava - Vitkovice, , Czechia

Cevni Chirurgie, Nemocnice Na Homolce

Prague, , Czechia

IKEM, Kardiologicka klinika

Prague, , Czechia

University Hospital Kralovske Vinobrady

Prague, , Czechia

Chirurgicka klinika IPVZ

Ústí nad Labem, , Czechia

Universitätsklinikum Bonn, Radiologische Universitätsklinik

Bonn, , Germany

Universitäts GefäßCentrum Uniklinikum Dresden

Dresden, , Germany

Klinik für Innere Medizin I - Angiologie / Kardiologie

Leipzig, , Germany

Life Care Institute of Medical Sciences and Research

Gujarat, , India

Gokula Metropolis Clinical Research Centre, M. S. Ramaiah Hospital

Karnataka, , India

Centro de Investigación y Atención Cardiovascular

Lima, , Peru

Hospital Nacional Edgardo Rebagliati Martins

Lima, , Peru

Hospital Nacional Guillermo Almenara Irigoyen-EsSalud

Lima, , Peru

Instituto Neuro Cardiovascular de las Americas

Lima, , Peru

Wojewodzki Szpital Specjalistyczny nr 4 w Bytomiu

Bytom, , Poland

Malopolskie Centrum Sercowo-Naczyniowe PAKS American Heart of Poland Sp. z o.o

Chrzanów, , Poland

Uniwersyleckie Centrum Kliniczne

Gdansk, , Poland

Szpital Kliniczny Przemienienia Panskiego Uniwersytetu Medycznego im. Karola Marcinkowskiego w Poznaniu

Poznan, , Poland

Zaklad Opieki Zdrowonej Ministerstwa Spraw Wewnetrznych i Administracji w Poznaniu

Poznan, , Poland

Samodzielny Publiczny Szpital Kliniczny Nr 2 PUM w Szczecinie

Szczecin, , Poland

Institutul de Urgenta pentru Boli Cardiovasculare "Prof.Dr.C.C.Iliescu"

Bucharest, , Romania

Institutul Inimii "Nicolae Stancioiu" Cluj-Napoca

Cluj-Napoca, , Romania

Inst.de Boli Cardiovasculare "Prof.I.M.Georgescu" Iasi

Iași, , Romania

Institutul de Boli Cardiovasculare si Transplant Mures

Târgu Mureş, , Romania

Institut za kardiovaskularne bolesti Dedinje

Belgrade, , Serbia

Klinicki Centar Srbije

Belgrade, , Serbia

Klinicki Centar Nis

Niš, , Serbia

Klinicki Centar Vojvodine

Novi Sad, , Serbia

Oddelenie diagnostickej a intervencnej radiologie, The National Institute of Cardiovascular Diseases

Bratislava, , Slovakia

The Eastern Slovak Institute of Cardiovascular Diseases

Košice, , Slovakia

Fundacion Hospital Alcorcon

Alcorcón, , Spain

Countries

United States; Belgium; Bulgaria; Czechia; Germany; India; Peru; Poland; Romania; Serbia; Slovakia; Spain

References

Comerota AJ, Davidovic L, Hanna K, Courtney KL, Shlansky-Goldberg RD. Phase 2, randomized, open-label study on catheter-directed thrombolysis with plasmin versus rtPA and placebo in acute peripheral arterial occlusion. J Drug Assess. 2019 Apr 9;8(1):43-54. doi: 10.1080/21556660.2019.1586402. eCollection 2019.

Reference Type: DERIVED

PMID: 31069128 (View on PubMed)

Other Identifiers

2010-019760-36

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

T05018-2004

Identifier Type: -

Identifier Source: org_study_id