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A Dose Escalation and Safety Study of Plasmin (Human) In Acute Lower Extremity Native Artery or Bypass Graft Occlusion (PRIORITY)

This study has been completed.
Sponsor:
Information provided by:
Grifols Therapeutics Inc.
ClinicalTrials.gov Identifier:
NCT00418483
First received: January 2, 2007
Last updated: July 8, 2010
Last verified: July 2010
  Purpose

The purpose of this study is to evaluate the safety of increasing doses of intra-thrombus Plasmin (Human) in acute peripheral arterial occlusion (aPAO). The ability of these Plasmin doses to dissolve the clots will be estimated by arteriography.


Condition Intervention Phase
Arterial Occlusive Diseases
Biological: Plasmin (Human) 25 mg
Biological: Plasmin (Human) 50 mg
Biological: Plasmin (Human) 75 mg
Biological: Plasmin (Human) 100 mg
Biological: Plasmin (Human) 125 mg
Biological: Plasmin (Human) 150 mg
Biological: Plasmin (Human) 175 mg
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Sequential Phase I/II Dose Escalation and Dose Selection Safety Study of Regional Intra-thrombus Plasmin (Human) Infusion In Acute Lower Extremity Native Artery or Bypass Graft Occlusion

Further study details as provided by Grifols Therapeutics Inc.:

Primary Outcome Measures:
  • Thrombolysis [ Time Frame: Approximately 5 hours after start of treatment ] [ Designated as safety issue: No ]
    Thrombolysis at the end of treatment compared to baseline by arteriography


Secondary Outcome Measures:
  • Thrombolysis [ Time Frame: Approximately 2 hours after start of treatment ] [ Designated as safety issue: No ]
    Thrombolysis at 120 minutes compared to baseline by arteriography

  • Avoidance of open surgical procedures [ Time Frame: 30 days ] [ Designated as safety issue: No ]
    Percent of subjects at Day 30 who avoid open surgical procedures

  • Avoidance of amputation [ Time Frame: 30 days ] [ Designated as safety issue: No ]
    Percent of subjects at Day 30 who avoid amputation

  • Avoidance of additional catheter-directed thrombolysis with a plasminogen activator or mechanical device thrombectomy [ Time Frame: 30 days ] [ Designated as safety issue: No ]
    Percent of subjects at Day 30 who avoided additional catheter-directed thrombolysis with a plasminogen activator or mechanical device thrombectomy.

  • Avoidance of both open surgical procedures and additional thrombolysis with a plasminogen activator or mechanical device thrombectomy. [ Time Frame: 30 days ] [ Designated as safety issue: No ]
    Percent of subjects at Day 30 who avoided both open surgical procedures and additional thrombolysis with a plasminogen activator or mechanical device thrombectomy.

  • Physiologic reperfusion defined as improvement in ankle brachial index (ABI) [ Time Frame: End of treatment, post intervention procedures, Day 1 to 2, Day 7, and Day 30 ] [ Designated as safety issue: No ]
    Physiologic reperfusion defined as improvement in ABI (increase of ≥ 0.15) determined at the end of treatment, post intervention procedures, Day 1 to 2, Day 7, and Day 30.

  • Patency assessed by duplex ultrasound imaging [ Time Frame: Day 7 and Day 30 ] [ Designated as safety issue: No ]
    Patency assessed by duplex ultrasound imaging on the affected leg on Day 7 and Day 30


Enrollment: 83
Study Start Date: March 2007
Study Completion Date: April 2010
Primary Completion Date: April 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Plasmin (Human) 25 mg
Plasmin (Human) 25 mg
Biological: Plasmin (Human) 25 mg
Plasmin (Human) 25 mg delivered via an infusion catheter into the thrombus over approximately 5 hours.
Other Names:
  • TAL-05-00018
  • BAY-57-9602
Experimental: Plasmin (Human) 50 mg
Plasmin (Human ) 50 mg
Biological: Plasmin (Human) 50 mg
Plasmin (Human) 50 mg delivered via an infusion catheter into the thrombus over approximately 5 hours.
Other Names:
  • TAL-05-00018
  • BAY-57-9602
Experimental: Plasmin (Human) 75 mg
Plasmin (Human) 75 mg
Biological: Plasmin (Human) 75 mg
Plasmin (Human) 75 mg delivered via an infusion catheter into the thrombus over approximately 5 hours.
Other Names:
  • TAL-05-00018
  • BAY-57-9602
Experimental: Plasmin (Human) 100 mg
Plasmin (Human) 100 mg
Biological: Plasmin (Human) 100 mg
Plasmin (Human) 100 mg
Other Names:
  • TAL-05-00018
  • BAY-57-9602
Experimental: Plasmin (Human) 125 mg
Plasmin (Human) 125 mg
Biological: Plasmin (Human) 125 mg
Plasmin (Human) 125 mg delivered via an infusion catheter into the thrombus over approximately 5 hours.
Other Names:
  • TAL-05-00018
  • BAY-57-9602
Experimental: Plasmin (Human) 150 mg
Plasmin (Human) 150 mg
Biological: Plasmin (Human) 150 mg
Plasmin (Human) 150 mg delivered via an infusion catheter into the thrombus over approximately 5 hours.
Other Names:
  • TAL-05-00018
  • BAY-57-9602
Experimental: Plasmin (Human) 175 mg
Plasmin (Human) 175 mg
Biological: Plasmin (Human) 175 mg
Plasmin (Human) 175 mg delivered via an infusion catheter into the thrombus over approximately 5 hours.
Other Names:
  • TAL-05-00018
  • BAY-57-9602

Detailed Description:

There is an unmet need for proven thrombolytic agent in acute peripheral arterial occlusion (aPAO). The current assortment of plasminogen activators are slow to dissolve clots in the leg, and may lead to bleeding complications. Plasmin is a direct thrombolytic that may act more quickly when infused directly into the clot and thus assist in restoring blood flow to the leg. There is a large reserve in blood alpha-2 antiplasmin in the blood to rapidly inactivate Plasmin outside of the clot. Plasmin has the potential for an improved bleeding risk profile in aPAO.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Age ≥ 18 years.
  • Women of childbearing potential must use adequate contraception for the duration of the study and must have a negative pregnancy test prior to study entry.
  • Unilateral limb ischemia: SVS acute ischemia Category I or IIa.
  • Onset of symptoms </= 14 days.
  • Thrombosed (non-embolic) infrainguinal graft (synthetic, autologous, or single outflow composite) or infrainguinal native artery. For native arteries, only occlusions of ≥ 10 cm in length are eligible.
  • Diagnosis of occlusive thrombus in the graft or artery by arteriography after Informed Consent is obtained.
  • Ability to traverse the thrombus with a guidewire.
  • Signed informed consent prior to study entry.

Exclusion Criteria:

  • Clinical evidence of significant disease that may interfere with the patient successfully completing the trial.
  • Women who are pregnant or lactating, or first 10 days post-partum.
  • Previous hemorrhagic stroke at any time. Thrombotic or embolic stroke or cerebrovascular events (including transient ischemic attack (TIA)) within one year.
  • Intracranial or spinal neuro-surgery, or severe intracranial trauma in the last 3 months. Major surgery, organ biopsy, or major trauma within the last 10 days. Lumbar puncture or non-compressible arterial puncture in the last 10 days. Intra-ocular surgery within the last 10 days.
  • Current bleeding diathesis. Active gastrointestinal or organ bleeding. Minor bleeding such as normal menses, cystitis, or minor hemorrhoidal bleeding are not exclusions.
  • Uncontrolled arterial hypertension, defined as a systolic blood pressure > 180 mmHg or diastolic blood pressure > 110 mmHg.
  • Known intracranial neoplasm, aneurysm, or arterio-venous malformation.
  • Platelet count < 75 x 10e9/L.
  • Occlusion of a graft within 6 months of placement.
  • Medically unable to tolerate an open vascular procedure.
  • Known prothrombotic condition.
  • Hemoglobin <10.0 g/dL
  • Impaired renal function or renal disease that constitutes a contraindication to contrast angiography, including creatinine > 2.0 mg/dL or subjects on renal dialysis.
  • Treatment with a glycoprotein IIb/IIIa class of platelet inhibitor within the past 5 days, for example, abciximab (ReoPro®), eptifibatide (Integrilin®) or tirofiban (Aggrastat®).
  • Treatment with warfarin (Coumadin®) and with an INR of >1.7 (elevated INR at screening may be corrected prior to study enrollment.)
  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: NCT00418483

Locations
United States, Ohio
Jobst Vascular Institute
Toledo, Ohio, United States, 43606
Sponsors and Collaborators
Grifols Therapeutics Inc.
Investigators
Principal Investigator: Anthony J Comerota, MD Jobst Vascular Center
  More Information

No publications provided

Responsible Party: Kim Hanna, MSc, Vice President of Clinical Development, Talecris Biotherapeutics
ClinicalTrials.gov Identifier: NCT00418483     History of Changes
Other Study ID Numbers: 050003
Study First Received: January 2, 2007
Last Updated: July 8, 2010
Health Authority: United States: Food and Drug Administration
Czech Republic: State Institute for Drug Control
United Kingdom: Medicines and Healthcare Products Regulatory Agency
Bulgaria: Bulgarian Drug Agency
South Africa: Medicines Control Council
Brazil: Ministry of Health
Argentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia Medica
Germany: Paul Ehrlich Institute for German Oversight Authority
Poland: Ministry of Health
Romania: National Medicines Agency
Hungary: National Institute of Pharmacy
Serbia and Montenegro: Agency for Drugs and Medicinal Devices

Keywords provided by Grifols Therapeutics Inc.:
thrombolytic
thrombolysis
acute peripheral arterial occlusion
peripheral vascular disease
thrombosis
endovascular

Additional relevant MeSH terms:
Arterial Occlusive Diseases
Cardiovascular Diseases
Vascular Diseases
Fibrinolysin
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 27, 2014