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

October 28, 2016 updated by: Grifols Therapeutics LLC

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

83

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Ohio
      • Toledo, Ohio, United States, 43606
        • Jobst Vascular Institute

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 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
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
Biological: Plasmin (Human) 100 mg
Plasmin (Human) 100 mg
Other Names:
  • TAL-05-00018
  • BAY-57-9602
Experimental: 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
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
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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Thrombolysis
Time Frame: Approximately 5 hours after start of treatment
Thrombolysis at the end of treatment compared to baseline by arteriography
Approximately 5 hours after start of treatment

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Thrombolysis
Time Frame: Approximately 2 hours after start of treatment
Thrombolysis at 120 minutes compared to baseline by arteriography
Approximately 2 hours after start of treatment
Avoidance of open surgical procedures
Time Frame: 30 days
Percent of subjects at Day 30 who avoid open surgical procedures
30 days
Avoidance of amputation
Time Frame: 30 days
Percent of subjects at Day 30 who avoid amputation
30 days
Avoidance of additional catheter-directed thrombolysis with a plasminogen activator or mechanical device thrombectomy
Time Frame: 30 days
Percent of subjects at Day 30 who avoided additional catheter-directed thrombolysis with a plasminogen activator or mechanical device thrombectomy.
30 days
Avoidance of both open surgical procedures and additional thrombolysis with a plasminogen activator or mechanical device thrombectomy.
Time Frame: 30 days
Percent of subjects at Day 30 who avoided both open surgical procedures and additional thrombolysis with a plasminogen activator or mechanical device thrombectomy.
30 days
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
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.
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
Patency assessed by duplex ultrasound imaging on the affected leg on Day 7 and Day 30
Day 7 and Day 30

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Grifols Therapeutics LLC

Investigators

  • Principal Investigator: Anthony J Comerota, MD, Jobst Vascular Center

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

March 1, 2007

Primary Completion (Actual)

April 1, 2010

Study Completion (Actual)

April 1, 2010

Study Registration Dates

First Submitted

January 2, 2007

First Submitted That Met QC Criteria

January 2, 2007

First Posted (Estimate)

January 4, 2007

Study Record Updates

Last Update Posted (Estimate)

October 31, 2016

Last Update Submitted That Met QC Criteria

October 28, 2016

Last Verified

October 1, 2016

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 050003

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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