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

NCT01222117 | Completed Phase 2 Results DMC

• 2 other identifiers: T05018-20042010-019760-36
• Study Type: interventional
• Target: 174
• Locations: 12 countries
• Sites: 39

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

Keywords

Acute Limb Ischemia

Outcome Measures

Primary Outcomes (1)

• The Proportion of Subjects With >50% Thrombolysis

  The proportion of subjects with \>50% thrombolysis at the end of treatment compared to baseline by arteriography.

  5 hours (Treatment Groups A, B, C, G, I, M) or 2 hours (Treatment Groups D, H, J)

Secondary Outcomes (1)

• 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

Study Arms (11)

Plasmin Open-label Treatment Group A

EXPERIMENTAL

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

Biological: Plasmin

Plasmin Open-label Treatment Group B

EXPERIMENTAL

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

Biological: Plasmin

Plasmin Open-label Treatment Group C

EXPERIMENTAL

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

Biological: Plasmin

Plasmin Open-label Treatment Group D

EXPERIMENTAL

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

Biological: Plasmin

Plasminogen Activator Blinded Group E

ACTIVE COMPARATOR

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

Biological: Plasminogen Activator

PA Placebo Blinded Treatment Arm F

PLACEBO COMPARATOR

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

Other: Placebo

Plasmin Open-label Treatment Group G

EXPERIMENTAL

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

Biological: Plasmin

Plasmin Open-label Treatment Group H

EXPERIMENTAL

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

Biological: Plasmin

Plasmin Open-label Treatment Group I

EXPERIMENTAL

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

Biological: Plasmin

Plasmin Open-label Treatment Group J

EXPERIMENTAL

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

Biological: Plasmin

Plasmin Open-label Treatment Group M

EXPERIMENTAL

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

Biological: Plasmin

Interventions

Plasmin BIOLOGICAL

Plasmin prepared in 0.9% saline for injection

Also known as: Plasmin (Human)

Plasmin Open-label Treatment Group A; Plasmin Open-label Treatment Group B; Plasmin Open-label Treatment Group C; Plasmin Open-label Treatment Group D; Plasmin Open-label Treatment Group G; Plasmin Open-label Treatment Group H; Plasmin Open-label Treatment Group I; Plasmin Open-label Treatment Group J; Plasmin Open-label Treatment Group M

Plasminogen Activator BIOLOGICAL

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

Also known as: tissue plasminogen activator (tPA), urokinase (UK)

Plasminogen Activator Blinded Group E

Placebo OTHER

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

Also known as: Normal saline

PA Placebo Blinded Treatment Arm F

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Grifols Therapeutics LLC: lead

Study Sites (39)

Kaleida Health System

Buffalo, New York, 14209, United States

Location

Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

Ziekenhuis Oost Limburg, Campus St. Jan

Genk, Limburg, 3600, Belgium

Location

Erasme Hospital, Brussels

Brussels, 1070, Belgium

Location

University Hospital Antwerp

Edegem, Belgium

Location

Chirurgie UZ Leuven

Leuven, Belgium

Location

Clinic of Vascular Surgery and Angiology

Sofia, 1309, Bulgaria

Location

Tokuda Hospital Sofia

Sofia, Bulgaria

Location

Vascular Centre Vitkovicka Nemocnice

Ostrava - Vitkovice, Czechia

Location

Cevni Chirurgie, Nemocnice Na Homolce

Prague, Czechia

Location

IKEM, Kardiologicka klinika

Prague, Czechia

Location

University Hospital Kralovske Vinobrady

Prague, Czechia

Location

Chirurgicka klinika IPVZ

Ústí nad Labem, Czechia

Location

Universitätsklinikum Bonn, Radiologische Universitätsklinik

Bonn, Germany

Location

Universitäts GefäßCentrum Uniklinikum Dresden

Dresden, Germany

Location

Klinik für Innere Medizin I - Angiologie / Kardiologie

Leipzig, Germany

Location

Life Care Institute of Medical Sciences and Research

Gujarat, India

Location

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

Karnataka, India

Location

Centro de Investigación y Atención Cardiovascular

Lima, Peru

Location

Hospital Nacional Edgardo Rebagliati Martins

Lima, Peru

Location

Hospital Nacional Guillermo Almenara Irigoyen-EsSalud

Lima, Peru

Location

Instituto Neuro Cardiovascular de las Americas

Lima, Peru

Location

Wojewodzki Szpital Specjalistyczny nr 4 w Bytomiu

Bytom, Poland

Location

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

Chrzanów, Poland

Location

Uniwersyleckie Centrum Kliniczne

Gdansk, Poland

Location

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

Poznan, Poland

Location

Zaklad Opieki Zdrowonej Ministerstwa Spraw Wewnetrznych i Administracji w Poznaniu

Poznan, Poland

Location

Samodzielny Publiczny Szpital Kliniczny Nr 2 PUM w Szczecinie

Szczecin, Poland

Location

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

Bucharest, Romania

Location

Institutul Inimii "Nicolae Stancioiu" Cluj-Napoca

Cluj-Napoca, Romania

Location

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

Iași, Romania

Location

Institutul de Boli Cardiovasculare si Transplant Mures

Târgu Mureş, Romania

Location

Institut za kardiovaskularne bolesti Dedinje

Belgrade, 11040, Serbia

Location

Klinicki Centar Srbije

Belgrade, Serbia

Location

Klinicki Centar Nis

Niš, Serbia

Location

Klinicki Centar Vojvodine

Novi Sad, Serbia

Location

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

Bratislava, 83348, Slovakia

Location

The Eastern Slovak Institute of Cardiovascular Diseases

Košice, Slovakia

Location

Fundacion Hospital Alcorcon

Alcorcón, Spain

Location

Related Publications (1)

• 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.

  PMID: 31069128 DERIVED

MeSH Terms

Interventions

Fibrinolysin; Plasminogen Activators; Tissue Plasminogen Activator; Urokinase-Type Plasminogen Activator; Saline Solution

Intervention Hierarchy (Ancestors)

Serine Endopeptidases; Endopeptidases; Peptide Hydrolases; Hydrolases; Enzymes; Enzymes and Coenzymes; Serine Proteases; Blood Coagulation Factors; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Biological Factors; Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Results Point of Contact

• Title: Kimberly Steinmann, MD
• Organization: Grifols Therapeutics

kimberly.steinmann@grifols.com

919-308-5444

Study Officials

• Kecia Courtney

  Grifols Therapeutics

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 13, 2010
• First Posted: October 18, 2010
• Study Start: December 1, 2010
• Primary Completion: December 1, 2015
• Study Completion: January 1, 2016
• Last Updated: January 16, 2017
• Results First Posted: May 30, 2016

Record last verified: 2016-11

Locations

CZ (5); DE (3); IN (2); BU (2); PL (6); RO (4); US (2); BE (4); PE (4); SE (4); SL (2); ES (1)