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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Grifols Therapeutics Inc.
ClinicalTrials.gov Identifier:
NCT01222117
First received: October 13, 2010
Last updated: August 18, 2014
Last verified: August 2014
  Purpose

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 the 150 mg dose.


Condition Intervention Phase
Acute Peripheral Arterial Occlusion
Biological: Plasmin
Biological: Plasminogen Activator
Other: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Grifols Therapeutics Inc.:

Primary Outcome Measures:
  • The proportion of subjects with >50% thrombolysis [ Time Frame: 5 hours ] [ Designated as safety issue: No ]
    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. [ Time Frame: 30 days ] [ Designated as safety issue: Yes ]
    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.


Estimated Enrollment: 160
Study Start Date: December 2010
Estimated Study Completion Date: July 2015
Estimated Primary Completion Date: April 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 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.
Biological: Plasmin
150 mg Plasmin prepared in 0.9% saline for injection
Other Name: Plasmin (Human)
Experimental: 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
Biological: Plasmin
150 mg Plasmin prepared in 0.9% saline for injection
Other Name: Plasmin (Human)
Experimental: Plasmin Open-label Treatment Group C
Open-label 150 mg Plasmin administered with proximal pulse; 5 hour infusion using 30 mL/hour infusion rate.
Biological: Plasmin
150 mg Plasmin prepared in 0.9% saline for injection
Other Name: Plasmin (Human)
Experimental: Plasmin Open-label Treatment Group D
Open-label 150 mg Plasmin administered with proximal pulse; 2-hour infusion using 35 mL/hour infusion rate
Biological: Plasmin
150 mg Plasmin prepared in 0.9% saline for injection
Other Name: Plasmin (Human)
Active Comparator: PA Blinded Treatment Group E
PA administered for five hours at a dose and volume according to the Investigator's clinical judgement/standard practice
Biological: Plasminogen Activator
Plasminogen activator used according to the Investigator's clinical judgment.
Other Names:
  • tissue plasminogen activator (tPA)
  • urokinase (UK)
Placebo Comparator: 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
Other: Placebo
Normal saline for injection at the same volume as the plasminogen activator.
Other Name: Normal saline
Experimental: Plasmin Open-label Treatment Group G
Open-label 150 mg Plasmin administered without pulsing; 5-hour infusion using 60 mL/hour infusion rate
Biological: Plasmin
150 mg Plasmin prepared in 0.9% saline for injection
Other Name: Plasmin (Human)
Experimental: Plasmin Open-label Treatment Group H
Open-label 150 mg Plasmin administered without pulsing; 2-hour infusion using 75 mL/hour infusion rate
Biological: Plasmin
150 mg Plasmin prepared in 0.9% saline for injection
Other Name: Plasmin (Human)

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01222117

  Show 39 Study Locations
Sponsors and Collaborators
Grifols Therapeutics Inc.
Investigators
Study Chair: Anthony J Comerota, MD Toledo Hospital
Study Chair: Victor Marder, MD University of California at Los Angeles
Study Chair: Richard Schlansky-Goldberg, MD University of Pennsylvania
  More Information

No publications provided

Responsible Party: Grifols Therapeutics Inc.
ClinicalTrials.gov Identifier: NCT01222117     History of Changes
Other Study ID Numbers: T05018-2004, 2010-019760-36
Study First Received: October 13, 2010
Last Updated: August 18, 2014
Health Authority: Belgium: Federal Agency for Medicinal Products and Health Products
Bulgaria: Bulgarian Drug Agency
Brazil: National Health Surveillance Agency
Czech Republic: State Institute for Drug Control
Germany: Paul-Ehrlich-Institut
India: Central Drugs Standard Control Organization
Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Peru: General Directorate of Pharmaceuticals, Devices, and Drugs
Romania: National Medicines Agency
Russia: Ministry of Health of the Russian Federation
Serbia and Montenegro: Agency for Drugs and Medicinal Devices
Slovakia: State Institute for Drug Control
Spain: Agencia Española de Medicamentos y Productos Sanitarios
Sri Lanka: Ministry of Healthcare & Nutrition
Ukraine: Ministry of Health
United States: Food and Drug Administration

Keywords provided by Grifols Therapeutics Inc.:
Acute Limb Ischemia

Additional relevant MeSH terms:
Arterial Occlusive Diseases
Cardiovascular Diseases
Vascular Diseases
Fibrinolysin
Plasminogen
Tissue Plasminogen Activator
Cardiovascular Agents
Fibrin Modulating Agents
Fibrinolytic Agents
Hematologic Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on November 24, 2014