Clinical trial NCT01222117: A Study of Intra-thrombus Plasmin (Human) In Acute Peripheral Arterial Occlusion
Official title: A Phase 2, Randomized, Open-label (With Blinded Plasminogen Activator and Placebo Control Groups) Study to Evaluate the Effects of Different Intra-thrombus Infusion Regimens of Plasmin (Human) Compared to Plasminogen Activator and Placebo In Patients With Acute Lower Extremity Native Artery or Bypass Graft Occlusion
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Acute Peripheral Arterial Occlusion
Keywords: Acute Limb Ischemia
Lead sponsor: Grifols Therapeutics LLC
Sponsor class: INDUSTRY
First posted: 2010-10-18
Enrollment: 174
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: The Proportion of Subjects With >50% Thrombolysis
timeFrame: 5 hours (Treatment Groups A, B, C, G, I, M) or 2 hours (Treatment Groups D, H, J)
Secondary outcomes:
measure: 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.
timeFrame: 30 days
Other outcomes:
Locations:
city: Buffalo
country: United States
facility: Kaleida Health System
state: New York
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Genk
country: Belgium
facility: Ziekenhuis Oost Limburg, Campus St. Jan
state: Limburg
city: Brussels
country: Belgium
facility: Erasme Hospital, Brussels
city: Edegem
country: Belgium
facility: University Hospital Antwerp
city: Leuven
country: Belgium
facility: Chirurgie UZ Leuven
city: Sofia
country: Bulgaria
facility: Clinic of Vascular Surgery and Angiology
city: Sofia
country: Bulgaria
facility: Tokuda Hospital Sofia
city: Ostrava - Vitkovice
country: Czech Republic
facility: Vascular Centre Vitkovicka Nemocnice
city: Prague
country: Czech Republic
facility: Cevni Chirurgie, Nemocnice Na Homolce
city: Prague
country: Czech Republic
facility: IKEM, Kardiologicka klinika
city: Prague
country: Czech Republic
facility: University Hospital Kralovske Vinobrady
city: Usti nad Labem
country: Czech Republic
facility: Chirurgicka klinika IPVZ
city: Bonn
country: Germany
facility: Universitätsklinikum Bonn, Radiologische Universitätsklinik
city: Dresden
country: Germany
facility: Universitäts GefäßCentrum Uniklinikum Dresden
city: Leipzig
country: Germany
facility: Klinik für Innere Medizin I - Angiologie / Kardiologie
city: Gujarat
country: India
facility: Life Care Institute of Medical Sciences and Research
city: Karnataka
country: India
facility: Gokula Metropolis Clinical Research Centre, M. S. Ramaiah Hospital
city: Lima
country: Peru
facility: Centro de Investigación y Atención Cardiovascular
city: Lima
country: Peru
facility: Hospital Nacional Edgardo Rebagliati Martins
city: Lima
country: Peru
facility: Hospital Nacional Guillermo Almenara Irigoyen-EsSalud
city: Lima
country: Peru
facility: Instituto Neuro Cardiovascular de las Americas
city: Bytom
country: Poland
facility: Wojewodzki Szpital Specjalistyczny nr 4 w Bytomiu
city: Chrzanow
country: Poland
facility: Malopolskie Centrum Sercowo-Naczyniowe PAKS American Heart of Poland Sp. z o.o
city: Gdansk
country: Poland
facility: Uniwersyleckie Centrum Kliniczne
city: Poznan
country: Poland
facility: Szpital Kliniczny Przemienienia Panskiego Uniwersytetu Medycznego im. Karola Marcinkowskiego w Poznaniu
city: Poznan
country: Poland
facility: Zaklad Opieki Zdrowonej Ministerstwa Spraw Wewnetrznych i Administracji w Poznaniu
city: Szczecin
country: Poland
facility: Samodzielny Publiczny Szpital Kliniczny Nr 2 PUM w Szczecinie
city: Bucuresti
country: Romania
facility: Institutul de Urgenta pentru Boli Cardiovasculare "Prof.Dr.C.C.Iliescu"
city: Cluj-Napoca
country: Romania
facility: Institutul Inimii "Nicolae Stancioiu" Cluj-Napoca
city: Iasi
country: Romania
facility: Inst.de Boli Cardiovasculare "Prof.I.M.Georgescu" Iasi
city: Targu Mures
country: Romania
facility: Institutul de Boli Cardiovasculare si Transplant Mures
city: Beograd
country: Serbia
facility: Institut za kardiovaskularne bolesti Dedinje
city: Beograd
country: Serbia
facility: Klinicki Centar Srbije
city: Nis
country: Serbia
facility: Klinicki Centar Nis
city: Novi Sad
country: Serbia
facility: Klinicki Centar Vojvodine
city: Bratislava
country: Slovakia
facility: Oddelenie diagnostickej a intervencnej radiologie, The National Institute of Cardiovascular Diseases
city: Kosice
country: Slovakia
facility: The Eastern Slovak Institute of Cardiovascular Diseases
city: Alcorcon
country: Spain
facility: Fundacion Hospital Alcorcon
Study officials:
affiliation: Grifols Therapeutics
name: Kecia Courtney
role: STUDY_DIRECTOR
References:
citation: 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.