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

Grifols

Status and phase: Completed; Phase 2

Conditions: Acute Peripheral Arterial Occlusion

Treatments: Biological: Plasminogen Activator; Biological: Plasmin; Other: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT01222117

2010-019760-36 (EudraCT Number)

T05018-2004

Details and patient eligibility

About

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.

Enrollment: 174 patients

Sex: All

Ages: 18+ years old

Volunteers: No 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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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174 participants in 11 patient groups, including a placebo group

Plasmin Open-label Treatment Group A

Experimental group

Description:

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

Treatment:

Biological: Plasmin

Plasmin Open-label Treatment Group B

Experimental group

Description:

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

Treatment:

Biological: Plasmin

Plasmin Open-label Treatment Group C

Experimental group

Description:

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

Treatment:

Biological: Plasmin

Plasmin Open-label Treatment Group D

Experimental group

Description:

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

Treatment:

Biological: Plasmin

Plasminogen Activator Blinded Group E

Active Comparator group

Description:

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

Treatment:

Biological: Plasminogen Activator

PA Placebo Blinded Treatment Arm F

Placebo Comparator group

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

Treatment:

Other: Placebo

Plasmin Open-label Treatment Group G

Experimental group

Description:

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

Treatment:

Biological: Plasmin

Plasmin Open-label Treatment Group H

Experimental group

Description:

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

Treatment:

Biological: Plasmin

Plasmin Open-label Treatment Group I

Experimental group

Description:

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

Treatment:

Biological: Plasmin

Plasmin Open-label Treatment Group J

Experimental group

Description:

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

Treatment:

Biological: Plasmin

Plasmin Open-label Treatment Group M

Experimental group

Description:

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

Treatment:

Biological: Plasmin