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

Phase 2

Completed

Conditions: Acute Peripheral Arterial Occlusion

Interventions: Biological: Plasmin
Biological: Plasminogen Activator
Other: Placebo

Registration Number: NCT01222117

Lead Sponsor: Grifols Therapeutics LLC

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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 174

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Plasmin Open-label Treatment Group A	Plasmin	Open-label 150 mg Plasmin administered without initial proximal pulse; 5-hour infusion using 10 mL/hour infusion rate.
Plasmin Open-label Treatment Group M	Plasmin	Open-label 250 mg Plasmin administered without pulsing; 5-hour infusion using 30 mL/hour infusion rate with balloon occlusion catheter
Plasmin Open-label Treatment Group D	Plasmin	Open-label 150 mg Plasmin administered with proximal pulse; 2-hour infusion using 35 mL/hour infusion rate
Plasminogen Activator Blinded Group E	Plasminogen Activator	PA administered for five hours at a dose and volume according to the Investigator's clinical judgement/standard practice
Plasmin Open-label Treatment Group G	Plasmin	Open-label 150 mg Plasmin administered without pulsing; 5-hour infusion using 60 mL/hour infusion rate
Plasmin Open-label Treatment Group C	Plasmin	Open-label 150 mg Plasmin administered with proximal pulse; 5 hour infusion using 30 mL/hour infusion rate.
Plasmin Open-label Treatment Group B	Plasmin	Open-label 150 mg Plasmin administered with initial proximal pulse; 5-hour infusion using 15 mL/hour infusion rate
PA Placebo Blinded Treatment Arm F	Placebo	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
Plasmin Open-label Treatment Group H	Plasmin	Open-label 150 mg Plasmin administered without pulsing; 2-hour infusion using 75 mL/hour infusion rate
Plasmin Open-label Treatment Group I	Plasmin	Open-label 150 mg Plasmin administered without pulsing; 5-hour infusion using 30 mL/hour infusion rate with balloon occlusion catheter
Plasmin Open-label Treatment Group J	Plasmin	Open-label 150 mg Plasmin administered without pulsing; 2-hour infusion using 35 mL/hour infusion rate with balloon occlusion catheter

Primary Outcome Measures

Name	Time	Method
The Proportion of Subjects With >50% Thrombolysis	5 hours (Treatment Groups A, B, C, G, I, M) or 2 hours (Treatment Groups D, H, J)	The proportion of subjects with \>50% thrombolysis at the end of treatment compared to baseline by arteriography.

Secondary Outcome Measures

Name	Time	Method
The Incidence of Major and Minor Bleeding Events, Deaths, Adverse Events, Serious Adverse Events, and Abnormal Laboratory Values as a Measure of Safety and Tolerability.	30 days	The incidence of major and minor bleeding events, deaths, adverse events, serious adverse events, and abnormal laboratory values as a measure of safety and tolerability.

Trial Locations

Locations (39): 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
Chirurgie UZ Leuven
🇧🇪
Leuven, Belgium
Tokuda Hospital Sofia
🇧🇬
Sofia, Bulgaria
University Hospital Kralovske Vinobrady
🇨🇿
Prague, Czech Republic
Universitätsklinikum Bonn, Radiologische Universitätsklinik
🇩🇪
Bonn, Germany
Chirurgicka klinika IPVZ
🇨🇿
Usti nad Labem, Czech Republic
Klinik für Innere Medizin I - Angiologie / Kardiologie
🇩🇪
Leipzig, Germany
Universitäts GefäßCentrum Uniklinikum Dresden
🇩🇪
Dresden, Germany
Hospital Nacional Guillermo Almenara Irigoyen-EsSalud
🇵🇪
Lima, Peru
Hospital Nacional Edgardo Rebagliati Martins
🇵🇪
Lima, Peru
Uniwersyleckie Centrum Kliniczne
🇵🇱
Gdansk, Poland
Malopolskie Centrum Sercowo-Naczyniowe PAKS American Heart of Poland Sp. z o.o
🇵🇱
Chrzanow, Poland
Zaklad Opieki Zdrowonej Ministerstwa Spraw Wewnetrznych i Administracji w Poznaniu
🇵🇱
Poznan, Poland
Institutul de Urgenta pentru Boli Cardiovasculare "Prof.Dr.C.C.Iliescu"
🇷🇴
Bucuresti, Romania
Samodzielny Publiczny Szpital Kliniczny Nr 2 PUM w Szczecinie
🇵🇱
Szczecin, Poland
Klinicki Centar Nis
🇷🇸
Nis, Serbia
Institutul Inimii "Nicolae Stancioiu" Cluj-Napoca
🇷🇴
Cluj-Napoca, Romania
Institutul de Boli Cardiovasculare si Transplant Mures
🇷🇴
Targu Mures, Romania
Klinicki Centar Srbije
🇷🇸
Beograd, Serbia
Institut za kardiovaskularne bolesti Dedinje
🇷🇸
Beograd, Serbia
Oddelenie diagnostickej a intervencnej radiologie, The National Institute of Cardiovascular Diseases
🇸🇰
Bratislava, Slovakia
The Eastern Slovak Institute of Cardiovascular Diseases
🇸🇰
Kosice, Slovakia
Fundacion Hospital Alcorcon
🇪🇸
Alcorcon, Spain
Cevni Chirurgie, Nemocnice Na Homolce
🇨🇿
Prague, Czech Republic
Wojewodzki Szpital Specjalistyczny nr 4 w Bytomiu
🇵🇱
Bytom, Poland
Life Care Institute of Medical Sciences and Research
🇮🇳
Gujarat, India
Centro de Investigación y Atención Cardiovascular
🇵🇪
Lima, Peru
Instituto Neuro Cardiovascular de las Americas
🇵🇪
Lima, Peru
Gokula Metropolis Clinical Research Centre, M. S. Ramaiah Hospital
🇮🇳
Karnataka, India
Inst.de Boli Cardiovasculare "Prof.I.M.Georgescu" Iasi
🇷🇴
Iasi, Romania
Clinic of Vascular Surgery and Angiology
🇧🇬
Sofia, Bulgaria
Vascular Centre Vitkovicka Nemocnice
🇨🇿
Ostrava - Vitkovice, Czech Republic
IKEM, Kardiologicka klinika
🇨🇿
Prague, Czech Republic
Klinicki Centar Vojvodine
🇷🇸
Novi Sad, Serbia
Szpital Kliniczny Przemienienia Panskiego Uniwersytetu Medycznego im. Karola Marcinkowskiego w Poznaniu
🇵🇱
Poznan, Poland
University Hospital Antwerp
🇧🇪
Edegem, Belgium