Study of the OPTtimum Duration of Acoustic Pulse ThromboLYSis ProcEdure in the Treatment of Acute Submassive Pulmonary Embolism
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 131
- 试验地点
- 41
- 主要终点
- Change From Baseline in the Right Ventricle (RV) Diameter-to-Left Ventricle (LV) Diameter Ratio to 48 ± 6 Hours After the Start of the APT Procedure
研究概览
简要总结
The objective is to determine the optimum dose of thrombolytic and duration of the ultrasound procedure (together defined as the APT Procedure) as a treatment for acute submassive pulmonary embolism (PE). Symptomatic submassive PE are participants with acute (less than or equal to [≤]14 days) PE with normal systemic arterial blood pressure (greater than [>] 90 mmHg) and evidence of RV dysfunction (right ventricular to left ventricular diameter ratio, that is; RV/LV ratio greater than or equal to [≥] 0.9). Participants with submassive PE will be randomized to one of four APT treatment groups: ultrasound of 2 and 6 hours (hrs) with r-tPA 2 milligrams (mg)/hr/catheter and ultrasound 4 and 6 hours with r-tPA, 1 mg/hr/catheter. On 08 June 2016, randomization into treatment group 4 (APT/6 hours-r-tPA/2 mg/hr/catheter) was closed following a reported intracranial hemorrhage (ICH) and death in a study participant in this arm.
详细描述
This study is designed to investigate the lowest recombinant tissue plasminogen activator (r-tPA) dose-ultrasound treatment time required to achieve the same reductions in thrombus burden and associated improvement in physiologic parameters demonstrated in ULTIMA (EKOS 08 [NCT01166997]) and SEATTLE II (EKOS 09 [NCT01513759]). Results of this study are intended to inform the study design for further studies of the Acoustic Pulse Thrombolysis (APT) Procedure. Analysis of the first 100 evaluable participants in the United States study suggested a degree of equipoise between treatment groups 1, 2 and 3 of the protocol and therefore the sample size has been extended and additional sites in the United Kingdom (UK) National Health Service included, with a view to adding to the findings of the OPTALYSE study from sites in the UK and increasing the number of participants treated by treatment protocol.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female greater than or equal to (≥) 18 years of age and less than or equal to (≤) 75 years of age.
- •CTA evidence of proximal PE (filling defect in at least one main or lobar pulmonary artery).
- •PE symptom duration ≤14 days.
- •Submassive PE: RV/LV diameter ≥ 0.9 from CTA and hemodynamically stable. For Participants in UK Sites: Submassive PE: RV/LV diameter ≥ 0.9 from CTA, hemodynamically stable and an elevated biomarker.
- •Must be treated within 48 hours of diagnosis of PE by CTA.
- •Signed Informed consent obtained from subject or Legally Authorized Representative.
排除标准
- •Stroke or transient ischemic attack (TIA), head trauma, or other active intracranial or intraspinal disease within one year.
- •Recent (within one month) or active bleeding from a major organ.
- •Major surgery within seven days of screening for study enrollment.
- •Clinician deems the subject high-risk for catastrophic bleeding.
- •History of heparin-induced thrombocytopenia (HIT).
- •Catheter-based pharmacomechanical treatment for PE within 3 days of study enrollment.
- •Systolic blood pressure (SBP) less than 90 mm Hg and/or use of vasopressors.
- •Cardiac arrest (including pulseless electrical activity and asystole) requiring active cardiopulmonary resuscitation (CPR).
- •Evidence of irreversible neurological compromise.
- •Life expectancy < one year. For Participants in UK Sites: Life expectancy < one year or enrollment in hospice care.
- •Use of thrombolytics or glycoprotein IIb/IIIa antagonists within 3 days prior to inclusion in the study.
- •Out-of-Range Laboratory Values: Hematocrit < 30%, Platelets < 100 thousand/microliter (μL), International normalized ratio (INR) >
- •Creatinine outside the normal range for the treating institution.
- •Participant is pregnant (positive pregnancy test; women of childbearing capacity must be tested) or breast feeding.
- •Active cancer (metastatic, progressive, or treated within the last 6 months). Exception: participants with non-melanoma primary skin cancers are eligible to participate in the study.
- •Known allergy, hypersensitivity, or thrombocytopenia from heparin, r-tPA, or iodinated contrast except for mild-moderate contrast allergies for which steroid pre-medication can be used.
- •History of any hematologic disease potentially involving abnormal platelet number or function.
结局指标
主要结局
Change From Baseline in the Right Ventricle (RV) Diameter-to-Left Ventricle (LV) Diameter Ratio to 48 ± 6 Hours After the Start of the APT Procedure
时间窗: Change from Baseline to 48 hrs ± 6 hours
Change from baseline in RV/LV will be determined by computed tomographic angiography (CTA).
Number of Participants With Major Bleeding Within 72 Hours After Initiating the APT Procedure
时间窗: Day 3 (within 72 hours after initiating the APT procedure)
Criteria for major bleeding events, as defined by the International Society on Thrombosis and Haemostasis (ISTH): 1. Fatal bleeding and/or; 2. Symptomatic bleeding in a critical area or organ (intracranial, intraspinal, intraocular, retroperitoneal, intra-articular or pericardial, or intramuscular with compartment syndrome) and/or; 3. Bleeding causing a fall in hemoglobin level of 20 grams/liter (g/L) or more, or leading to transfusion of two or more units of whole blood or red blood cells.
次要结局
- Percentage of Participants With Collapse of the Inferior Vena Cava (IVC) With Respiration at Days 0, 2, 30, 90, and 365, as Assessed by Echocardiograph(Baseline (Day -2 [within -48 hrs of APT start]), Day 0 (within 4 hours after APT end), Day 2 (48 [± 6] hrs of APT start), Day 30 (± 5 days), Day 90 (± 10 days) and Day 365 (± 14 days))
- Change in 6 Minute Walk (6MW) Distance From Day 30 to Day 90 and 365(Days 30, 90, 365)
- Change From Baseline in Tricuspid Annular Plane Systolic Excursion (TAPSE) at Days 0, 2, 30, 90, and 365, as Assessed by Echocardiograph(Baseline (Day -2 [within -48 hrs of APT start]), Day 0 (within 4 hours after APT end), Day 2 (48 [± 6] hrs of APT start), Day 30 (± 5 days), Day 90 (± 10 days) and Day 365 (± 14 days))
- Change in Borg Scale Score Before and After 6MW Distance Test at Days 30, 90, and 365(Days 30, 90, and 365)
- Number of Participants Who Received Oxygen Therapy(Days 30, 90, and 365)
- Percentage of Participants With Treatment Success of an APT Procedure(From Baseline up to Day 30)
- For Participants of UK Sites:Change in EuroQual - 5 Dimensions - 5 Levels (EQ-5D-5L) Score From Day 30 to Day 365(Day 30, Day 365)
- Change From Baseline in RV/LV at Days 0, 2, 30, 90, and 365, as Assessed by Echocardiograph.(Baseline (Day -2 [within -48 hrs of APT start]), Day 0 (within 4 hours after APT end), Day 2 (48 [± 6] hrs of APT start), Day 30 (± 5 days), Day 90 (± 10 days) and Day 365 (± 14 days))
- Change From Baseline in Thrombus Burden by Miller Score as Assessed by Pulmonary Arteriogram (PAgram) at Day 0(Baseline, Day 0 (within 4 hours after APT end))
- Change in Pulmonary Embolism Quality of Life (PEmb-QOL) Score From Day 30 to Day 365(Day 30, Day 365)
- Number of Participants Who Die Due to Any Cause(From Baseline up to Day 365)
- Healthcare Resource Utilization: Number of Healthcare Professionals (HCP) Visits for Venous Thromboembolism (VTE) After Hospitalization and During 12month Follow-up. (UK Participants Only)(From Day 30 up to Day 365)
- Healthcare Resource Utilization: Number of Healthcare Professionals (HCP) Visits for Venous Thromboembolism (VTE) After Hospitalization and During 12 Month Follow-up. (UK Participants Only)(From Day 30 up to Day 365)
- Change From Baseline in Estimated Right Ventricular Systolic Pressure (RVSP) at Days 0, 2, 30, 90, and 365, as Assessed by Echocardiograph(Baseline (Day -2 [within -48 hrs of APT start]), Day 0 (within 4 hours after APT end), Day 2 (48 [± 6] hrs of APT start), Day 30 (± 5 days), Day 90 (± 10 days) and Day 365 (± 14 days))
- Change From Baseline in Thrombus Burden by Modified Miller Score as Assessed by CTA Scan at 48 ± 6 Hours After the Start of the APT Procedure(From Baseline to 48 hrs ± 6 hours)
- For Participants of UK Sites: Time From Hospital Admission to Diagnosis of PE(From Baseline through Day 3)
- Change in Participant Reported Outcomes Measurement Information System Physical Function (PROMIS-PF) 6b Score From Day 30 to Day 365(Day 30, Day 365)
- Number of Participants Who Encountered Technical Procedural Complications(From device placement through Day 2)
- Number of Participants With Symptomatic Recurrent Pulmonary Embolism (Per Adjudication)(From Baseline up to Day 365)
- For Participants of UK Sites: Freedom From Major Harm Occurring Between Enrolment and 30 Days(From Baseline up to Day 30)
- For Participants of UK Sites: Time From Diagnostic Computed Tomography (CT) Scan to Initiation of Treatment for PE(From Baseline through Day 3)
- For Participants of UK Sites: Time in Each Level of Care (Level 0 and 1; Level 2; and/or Level 3) Through Discharge(From Baseline up to Hospital Discharge)
- Healthcare Resource Utilization: Team Managing the Participant During Hospitalization - Number of Healthcare Professional (HCP) Specialties Involved. (UK Participants Only)(From Baseline up to Day 365)
- Healthcare Resource Utilization: Number of Hospital Re-Admissions After Hospitalization and During 12 Month Follow-up. (UK Participants Only)(From Day 30 up to Day 365)
- Healthcare Resource Utilization: Duration of Hospital Re-Admissions After Hospitalization and During 12 Month Follow-up. (UK Participants Only)(From Day 30 through Day 365)