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

Primary Purpose

Acute Peripheral Arterial Occlusion

Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Plasmin
Plasminogen Activator
Placebo
Sponsored by
Grifols Therapeutics LLC
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Acute Peripheral Arterial Occlusion focused on measuring Acute Limb Ischemia

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Kaleida Health System
  • Cleveland Clinic
  • Ziekenhuis Oost Limburg, Campus St. Jan
  • Erasme Hospital, Brussels
  • University Hospital Antwerp
  • Chirurgie UZ Leuven
  • Clinic of Vascular Surgery and Angiology
  • Tokuda Hospital Sofia
  • Vascular Centre Vitkovicka Nemocnice
  • Cevni Chirurgie, Nemocnice Na Homolce
  • IKEM, Kardiologicka klinika
  • University Hospital Kralovske Vinobrady
  • Chirurgicka klinika IPVZ
  • Universitätsklinikum Bonn, Radiologische Universitätsklinik
  • Universitäts GefäßCentrum Uniklinikum Dresden
  • Klinik für Innere Medizin I - Angiologie / Kardiologie
  • Life Care Institute of Medical Sciences and Research
  • Gokula Metropolis Clinical Research Centre, M. S. Ramaiah Hospital
  • Centro de Investigación y Atención Cardiovascular
  • Hospital Nacional Edgardo Rebagliati Martins
  • Hospital Nacional Guillermo Almenara Irigoyen-EsSalud
  • Instituto Neuro Cardiovascular de las Americas
  • Wojewodzki Szpital Specjalistyczny nr 4 w Bytomiu
  • Malopolskie Centrum Sercowo-Naczyniowe PAKS American Heart of Poland Sp. z o.o
  • Uniwersyleckie Centrum Kliniczne
  • Szpital Kliniczny Przemienienia Panskiego Uniwersytetu Medycznego im. Karola Marcinkowskiego w Poznaniu
  • Zaklad Opieki Zdrowonej Ministerstwa Spraw Wewnetrznych i Administracji w Poznaniu
  • Samodzielny Publiczny Szpital Kliniczny Nr 2 PUM w Szczecinie
  • Institutul de Urgenta pentru Boli Cardiovasculare "Prof.Dr.C.C.Iliescu"
  • Institutul Inimii "Nicolae Stancioiu" Cluj-Napoca
  • Inst.de Boli Cardiovasculare "Prof.I.M.Georgescu" Iasi
  • Institutul de Boli Cardiovasculare si Transplant Mures
  • Institut za kardiovaskularne bolesti Dedinje
  • Klinicki Centar Srbije
  • Klinicki Centar Nis
  • Klinicki Centar Vojvodine
  • Oddelenie diagnostickej a intervencnej radiologie, The National Institute of Cardiovascular Diseases
  • The Eastern Slovak Institute of Cardiovascular Diseases
  • Fundacion Hospital Alcorcon

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm 7

Arm 8

Arm 9

Arm 10

Arm 11

Arm Type

Experimental

Experimental

Experimental

Experimental

Active Comparator

Placebo Comparator

Experimental

Experimental

Experimental

Experimental

Experimental

Arm Label

Plasmin Open-label Treatment Group A

Plasmin Open-label Treatment Group B

Plasmin Open-label Treatment Group C

Plasmin Open-label Treatment Group D

Plasminogen Activator Blinded Group E

PA Placebo Blinded Treatment Arm F

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

Arm Description

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

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

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

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

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

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

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

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

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

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

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

Outcomes

Primary Outcome Measures

The Proportion of Subjects With >50% Thrombolysis
The proportion of subjects with >50% thrombolysis at the end of treatment compared to baseline by arteriography.

Secondary Outcome Measures

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.
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.

Full Information

First Posted
October 13, 2010
Last Updated
November 28, 2016
Sponsor
Grifols Therapeutics LLC
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1. Study Identification

Unique Protocol Identification Number
NCT01222117
Brief Title
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

2. Study Status

Record Verification Date
November 2016
Overall Recruitment Status
Completed
Study Start Date
December 2010 (undefined)
Primary Completion Date
December 2015 (Actual)
Study Completion Date
January 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Grifols Therapeutics LLC

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acute Peripheral Arterial Occlusion
Keywords
Acute Limb Ischemia

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
174 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Plasmin Open-label Treatment Group A
Arm Type
Experimental
Arm Description
Open-label 150 mg Plasmin administered without initial proximal pulse; 5-hour infusion using 10 mL/hour infusion rate.
Arm Title
Plasmin Open-label Treatment Group B
Arm Type
Experimental
Arm Description
Open-label 150 mg Plasmin administered with initial proximal pulse; 5-hour infusion using 15 mL/hour infusion rate
Arm Title
Plasmin Open-label Treatment Group C
Arm Type
Experimental
Arm Description
Open-label 150 mg Plasmin administered with proximal pulse; 5 hour infusion using 30 mL/hour infusion rate.
Arm Title
Plasmin Open-label Treatment Group D
Arm Type
Experimental
Arm Description
Open-label 150 mg Plasmin administered with proximal pulse; 2-hour infusion using 35 mL/hour infusion rate
Arm Title
Plasminogen Activator Blinded Group E
Arm Type
Active Comparator
Arm Description
PA administered for five hours at a dose and volume according to the Investigator's clinical judgement/standard practice
Arm Title
PA Placebo Blinded Treatment Arm F
Arm Type
Placebo Comparator
Arm Description
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
Arm Title
Plasmin Open-label Treatment Group G
Arm Type
Experimental
Arm Description
Open-label 150 mg Plasmin administered without pulsing; 5-hour infusion using 60 mL/hour infusion rate
Arm Title
Plasmin Open-label Treatment Group H
Arm Type
Experimental
Arm Description
Open-label 150 mg Plasmin administered without pulsing; 2-hour infusion using 75 mL/hour infusion rate
Arm Title
Plasmin Open-label Treatment Group I
Arm Type
Experimental
Arm Description
Open-label 150 mg Plasmin administered without pulsing; 5-hour infusion using 30 mL/hour infusion rate with balloon occlusion catheter
Arm Title
Plasmin Open-label Treatment Group J
Arm Type
Experimental
Arm Description
Open-label 150 mg Plasmin administered without pulsing; 2-hour infusion using 35 mL/hour infusion rate with balloon occlusion catheter
Arm Title
Plasmin Open-label Treatment Group M
Arm Type
Experimental
Arm Description
Open-label 250 mg Plasmin administered without pulsing; 5-hour infusion using 30 mL/hour infusion rate with balloon occlusion catheter
Intervention Type
Biological
Intervention Name(s)
Plasmin
Other Intervention Name(s)
Plasmin (Human)
Intervention Description
Plasmin prepared in 0.9% saline for injection
Intervention Type
Biological
Intervention Name(s)
Plasminogen Activator
Other Intervention Name(s)
tissue plasminogen activator (tPA), urokinase (UK)
Intervention Description
Plasminogen activator used according to the Investigator's clinical judgment.
Intervention Type
Other
Intervention Name(s)
Placebo
Other Intervention Name(s)
Normal saline
Intervention Description
Normal saline for injection at the same volume as the plasminogen activator.
Primary Outcome Measure Information:
Title
The Proportion of Subjects With >50% Thrombolysis
Description
The proportion of subjects with >50% thrombolysis at the end of treatment compared to baseline by arteriography.
Time Frame
5 hours (Treatment Groups A, B, C, G, I, M) or 2 hours (Treatment Groups D, H, J)
Secondary Outcome Measure Information:
Title
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.
Description
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.
Time Frame
30 days

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Kecia Courtney
Organizational Affiliation
Grifols Therapeutics
Official's Role
Study Director
Facility Information:
Facility Name
Kaleida Health System
City
Buffalo
State/Province
New York
ZIP/Postal Code
14209
Country
United States
Facility Name
Cleveland Clinic
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44195
Country
United States
Facility Name
Ziekenhuis Oost Limburg, Campus St. Jan
City
Genk
State/Province
Limburg
ZIP/Postal Code
3600
Country
Belgium
Facility Name
Erasme Hospital, Brussels
City
Brussels
ZIP/Postal Code
1070
Country
Belgium
Facility Name
University Hospital Antwerp
City
Edegem
Country
Belgium
Facility Name
Chirurgie UZ Leuven
City
Leuven
Country
Belgium
Facility Name
Clinic of Vascular Surgery and Angiology
City
Sofia
ZIP/Postal Code
1309
Country
Bulgaria
Facility Name
Tokuda Hospital Sofia
City
Sofia
Country
Bulgaria
Facility Name
Vascular Centre Vitkovicka Nemocnice
City
Ostrava - Vitkovice
Country
Czech Republic
Facility Name
Cevni Chirurgie, Nemocnice Na Homolce
City
Prague
Country
Czech Republic
Facility Name
IKEM, Kardiologicka klinika
City
Prague
Country
Czech Republic
Facility Name
University Hospital Kralovske Vinobrady
City
Prague
Country
Czech Republic
Facility Name
Chirurgicka klinika IPVZ
City
Usti nad Labem
Country
Czech Republic
Facility Name
Universitätsklinikum Bonn, Radiologische Universitätsklinik
City
Bonn
Country
Germany
Facility Name
Universitäts GefäßCentrum Uniklinikum Dresden
City
Dresden
Country
Germany
Facility Name
Klinik für Innere Medizin I - Angiologie / Kardiologie
City
Leipzig
Country
Germany
Facility Name
Life Care Institute of Medical Sciences and Research
City
Gujarat
Country
India
Facility Name
Gokula Metropolis Clinical Research Centre, M. S. Ramaiah Hospital
City
Karnataka
Country
India
Facility Name
Centro de Investigación y Atención Cardiovascular
City
Lima
Country
Peru
Facility Name
Hospital Nacional Edgardo Rebagliati Martins
City
Lima
Country
Peru
Facility Name
Hospital Nacional Guillermo Almenara Irigoyen-EsSalud
City
Lima
Country
Peru
Facility Name
Instituto Neuro Cardiovascular de las Americas
City
Lima
Country
Peru
Facility Name
Wojewodzki Szpital Specjalistyczny nr 4 w Bytomiu
City
Bytom
Country
Poland
Facility Name
Malopolskie Centrum Sercowo-Naczyniowe PAKS American Heart of Poland Sp. z o.o
City
Chrzanow
Country
Poland
Facility Name
Uniwersyleckie Centrum Kliniczne
City
Gdansk
Country
Poland
Facility Name
Szpital Kliniczny Przemienienia Panskiego Uniwersytetu Medycznego im. Karola Marcinkowskiego w Poznaniu
City
Poznan
Country
Poland
Facility Name
Zaklad Opieki Zdrowonej Ministerstwa Spraw Wewnetrznych i Administracji w Poznaniu
City
Poznan
Country
Poland
Facility Name
Samodzielny Publiczny Szpital Kliniczny Nr 2 PUM w Szczecinie
City
Szczecin
Country
Poland
Facility Name
Institutul de Urgenta pentru Boli Cardiovasculare "Prof.Dr.C.C.Iliescu"
City
Bucuresti
Country
Romania
Facility Name
Institutul Inimii "Nicolae Stancioiu" Cluj-Napoca
City
Cluj-Napoca
Country
Romania
Facility Name
Inst.de Boli Cardiovasculare "Prof.I.M.Georgescu" Iasi
City
Iasi
Country
Romania
Facility Name
Institutul de Boli Cardiovasculare si Transplant Mures
City
Targu Mures
Country
Romania
Facility Name
Institut za kardiovaskularne bolesti Dedinje
City
Beograd
ZIP/Postal Code
11040
Country
Serbia
Facility Name
Klinicki Centar Srbije
City
Beograd
Country
Serbia
Facility Name
Klinicki Centar Nis
City
Nis
Country
Serbia
Facility Name
Klinicki Centar Vojvodine
City
Novi Sad
Country
Serbia
Facility Name
Oddelenie diagnostickej a intervencnej radiologie, The National Institute of Cardiovascular Diseases
City
Bratislava
ZIP/Postal Code
83348
Country
Slovakia
Facility Name
The Eastern Slovak Institute of Cardiovascular Diseases
City
Kosice
Country
Slovakia
Facility Name
Fundacion Hospital Alcorcon
City
Alcorcon
Country
Spain

12. IPD Sharing Statement

Citations:
PubMed Identifier
31069128
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.
Results Reference
derived

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

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