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

Arterial Occlusive Diseases Clinical Trial

— PRIORITY  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00418483
• Other study ID #: 050003
• Status: Completed
• Phase: Phase 1
• First received: January 2, 2007
• Last updated: October 28, 2016
• Start date: March 2007
• Est. completion date: April 2010

Study information

• Verified date: October 2016
• Source: Grifols Therapeutics Inc.
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationCzech Republic: State Institute for Drug ControlUnited Kingdom: Medicines and Healthcare Products Regulatory AgencyBulgaria: Bulgarian Drug AgencySouth Africa: Medicines Control CouncilBrazil: Ministry of HealthArgentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia MedicaGermany: Paul Ehrlich Institute for German Oversight AuthorityPoland: Ministry of HealthRomania: National Medicines AgencyHungary: National Institute of PharmacySerbia and Montenegro: Agency for Drugs and Medicinal Devices
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 83
• Est. completion date: April 2010
• Est. primary completion date: April 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Arterial Occlusive Diseases

Intervention

Biological:
• Plasmin (Human) 25 mg
Plasmin (Human) 25 mg delivered via an infusion catheter into the thrombus over approximately 5 hours.
• Plasmin (Human) 50 mg
Plasmin (Human) 50 mg delivered via an infusion catheter into the thrombus over approximately 5 hours.
• Plasmin (Human) 75 mg
Plasmin (Human) 75 mg delivered via an infusion catheter into the thrombus over approximately 5 hours.
• Plasmin (Human) 100 mg
Plasmin (Human) 100 mg
• Plasmin (Human) 125 mg
Plasmin (Human) 125 mg delivered via an infusion catheter into the thrombus over approximately 5 hours.
• Plasmin (Human) 150 mg
Plasmin (Human) 150 mg delivered via an infusion catheter into the thrombus over approximately 5 hours.
• Plasmin (Human) 175 mg
Plasmin (Human) 175 mg delivered via an infusion catheter into the thrombus over approximately 5 hours.

Locations

Country	Name	City	State
United States	Jobst Vascular Institute	Toledo	Ohio

Sponsors (1)

Lead Sponsor	Collaborator
Grifols Therapeutics Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Thrombolysis	Thrombolysis at the end of treatment compared to baseline by arteriography	Approximately 5 hours after start of treatment	No
Secondary	Thrombolysis	Thrombolysis at 120 minutes compared to baseline by arteriography	Approximately 2 hours after start of treatment	No
Secondary	Avoidance of open surgical procedures	Percent of subjects at Day 30 who avoid open surgical procedures	30 days	No
Secondary	Avoidance of amputation	Percent of subjects at Day 30 who avoid amputation	30 days	No
Secondary	Avoidance of additional catheter-directed thrombolysis with a plasminogen activator or mechanical device thrombectomy	Percent of subjects at Day 30 who avoided additional catheter-directed thrombolysis with a plasminogen activator or mechanical device thrombectomy.	30 days	No
Secondary	Avoidance of both open surgical procedures and additional thrombolysis with a plasminogen activator or mechanical device thrombectomy.	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	No
Secondary	Physiologic reperfusion defined as improvement in ankle brachial index (ABI)	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	No
Secondary	Patency assessed by duplex ultrasound imaging	Patency assessed by duplex ultrasound imaging on the affected leg on Day 7 and Day 30	Day 7 and Day 30	No