T05018-2004: A Phase 2, Randomized, Open-label (with BlindedPlasminogen 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 Grafi Occlusion
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 100
- 试验地点
- 16
- 主要终点
- The proportion of subjects with 50% thrombolysis at the end of treatment compared to baseline by arteriography.
研究概览
简要总结
This is a Phase 2, multi-center, multi-national, randomized, open-label study (with blinded PA and PA Placebo groups) of Plasmin in subjects with acute angiographically confirmed lower extremity native artery or bypass graft occlusion. Subjects will be enrolled into one of six parallel treatment groups: four Plasmin Treatment groups differing only in administration technique and two blinded groups (a Blinded PA Treatment Group and a Blinded PA Placebo Group). The administration regimens for the Plasmin groups have been designed to examine the effect of different infusion catheter positions, different Plasmin pulse regimens, and different rates of Plasmin continuous infusion/volume on the thrombolytic activity and safety of Plasmin treatment. Acute lower extremity ischemia will be diagnosed by a PAO assessment examination for the purpose of classifying the subject into the Society for Vascular Surgery (SVS) acute limb ischemia category. This includes findings of sensory loss,muscle weakness, and presence or absence of arterial and venous Doppler signals (Doppler is optional at screening and baseline). Ischemic signs and symptoms of pain, paresthesias, paralysis, poikilothermia, pallor, and pulselessness will be documented. Approximately 100 subjects, ages of 18 or greater, are planned to be randomized in a 2:2:2:2:1:1 ratio to four Plasmin treatment groups (Groups A, B, C, and D, 20 subjects/group), one Blinded PA Treatment Group (Group E, 10 subjects/group), and one Blinded PA Placebo Group (Group F, 10 subjects/group) at investigative sites in multiple countries. Approximately eighty (80) subjects will be dosed with Plasmin, approximately ten (10) subjects will be dosed with PA and approximately ten (10) subjects will be dosed with PA Placebo. Subjects will be stratified at randomization into each treatment group by occluded lower extremity blood vessel type (native artery or graft) to ensure approximate equal balance of each presenting vessel type across treatment groups. Globally following countries are involved in this clinical trial: India, Sri Lanka, Belgium, Bulgaria, Czech Republic, Germany, Poland, Romania, Russia, Serbia, Slovakia, Spain, Ukraine, Brazil and Peru.
研究设计
- 研究类型
- Interventional
- 分配方式
- Computer generated randomization
- 盲法
- Open Label
入排标准
- 年龄范围
- 18.00 Year(s) 至 99.00 Year(s)（—）
- 性别
- All
入选标准
- •Inclusion Criteria
- •Unilateral limb ischemia: symptomatic, SVS acute ischemic Categories I and IIa
- •Onset of symptoms less than or equal to 14 days
- •Thrombosed (non-embolic) infrainguinal graft (synthetic, autologous, or single outflow composite) or infrainguinal native artery.
- •For native arteries, occlusions of greater than or equal to 10 cm in length are eligible.
- •Diagnosis of occlusive thrombus in the graft or artery by arteriography after informed consent is obtained
- •Ability to access the thrombus with the infusion catheter and successfully embed the infusion segment of the infusion catheter.
- •Subject must be able to give written informed consent prior to study entry
- •Age greater than or equal to 18 years
- •Women of child bearing potential must use adequate contraception for the duration of the study and must have a negative pregnancy test prior to study entry (Since there is no upper age limit defined for this trial for the CTRI registration purpose we have included the upper age limit to be considered as 99 years).
排除标准
- •Exclusion CriteriaGeneral
- •Any medical or social condition that may interfere with the subject successfully completing the study
- •Women who are pregnant or lactating, or first 10 days post-partumPast Medical History
- •Cardiopulmonary resuscitation in the last year
- •Previous systemic or anaphylactoid allergy to contrast agent, streptokinase, or blood products (subjects allergic to shellfish or iodine are permitted to enter the study).
- •Contraindications To Thrombolysis
- •Ineligible for thrombolytic treatment for any reason.
- •Specific exclusions include:a.
- •History of hemorrhagic strokeb.
- •Thrombotic or embolic stroke or cerebrovascular events (including transient ischemic attack [TIA]) within the past yearc.
- •Intracranial or spinal neuro-surgery or severe intracranial trauma in the past 3 monthsd.
- •Major surgery, organ biopsy, or major trauma within the past 10 dayse.
- •Lumbar puncture or non-compressible arterial puncture in the past 10 daysf.
- •Intra-ocular surgery within the past 10 daysg.
- •Active gastrointestinal or organ bleeding.
- •Minor bleeding such as normal menses, cystitis, or minor hemorrhoidal bleeding are not exclusionsh.
- •Uncontrolled arterial hypertension, defined as a systolic blood pressure >180 millimeters of mercury (mmHg) or diastolic blood pressure >110 mmHg. Thesubject will be eligible if the hypertension is controlled at the time of study enrollment.i. Known intracranial neoplasm, aneurysm, or arterio-venous malformationj.
- •Current bleeding diathesisk.
- •Platelet count <75 x 109/L Current Medical Status
- •Active graft infection
- •Occlusion occurred within one month of synthetic graft placement
- •A sequential composite graft with dual outflows to correct multiple occlusions
- •Known prothrombotic state, e.g., anti-cardiolipin antibody, human immunodeficiency virus (HIV)-associated peripheral vascular disease
- •Known contraindication to heparin (e.g., history of heparin-induced thrombocytopenia)
- •Hemoglobin <10.0 g/dL (low hemoglobin at screening in the absence of active bleeding may be corrected by transfusion).
- •Hemoglobin testing can be repeated.
- •Impaired renal function or renal disease that constitutes a contraindication to contrast arteriography, including a screen/baseline creatinine of >2.0 mg/dL.
- •Creatinine may be repeated following hydration for prerenal azotemia.Prior/Concurrent Therapy
- •Previous treatment with Plasmin
- •Treatment with full dose plasminogen activator (e.g., streptokinase (e.g., Streptase®, Kabikinase®), anistreplase (Eminase®), alteplase (e.g., Activase®), reteplase (e.g., Retavase®), tenecteplase (TNKase?), urokinase (UK, [Abbokinase®]) within the last 48 hours
- •Treatment with a glycoprotein IIb/IIIa class of platelet inhibitor within 5 days prior to study entry or at any time during the study, e.g., abciximab (ReoPro®),eptifibatide (Integrilin®) or tirofiban (Aggrastat®)
- •Treatment with oral anticoagulants (e.g., warfarin, acenocumarol), and with an international normalized ratio (INR) of >1.7 (elevated INR at screening may be corrected prior to study enrollment).
- •INR testing can be repeated.Others
- •Participation in another clinical study within 30 days prior to entry (imaging studies without investigative treatment are permitted), or concomitant participation in another study.20.
结局指标
主要结局
The proportion of subjects with 50% thrombolysis at the end of treatment compared to baseline by arteriography.
时间窗: 5 hr timepoint
次要结局
- 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.(DAY 30)