Impedance Threshold Value for Improving Standard CPR

描述（由申请人提供）：尽管基本和高级生命支持的广泛应用，在美国每天仍有超过1000名患者死于院外心脏骤停。即使他们接受了标准的心肺复苏（sCPR），这些患者的平均全国生存率仍然<5%。申请人已经开发了两种新的心肺复苏术装置，吸气阻抗阈值装置（ITD）和主动压缩减压（ACD）心肺复苏术装置，与sCPR联合使用时，心脏和大脑的血流量增加了四倍。过渡段是一个孩子的拳头大小，它通过面罩或呼吸管连接到气道。ACD心肺复苏术是一种手持式装置，它像双手一样压迫胸部，但由于它有一个附着在胸部的吸盘，可以促进主动和充分的胸壁反冲。这些装置通过增加sCPR胸壁反冲阶段的胸内负压或胸内真空的程度和持续时间协同工作，从而在每次胸部按压后更有效地重新填充心脏。仅关注ITD + sCPR的2期临床试验表明，无脉电活动初始心律患者的重症监护病房住院率（主要研究终点）从19%增加到52% （p=0.02）。第二阶段的研究进一步发现，在sCPR期间，通气频率和持续时间往往过高，每次按压后胸部往往不能完全后坐。每一种常见的临床错误都被首次电子记录下来，然后在心脏骤停的后续动物研究中被证明是有害的，如果不是致命的。基于这些第二阶段的结果，申请人通过增加通气定时灯来改进过渡段，以指导适当的通气，并在研究设计中增加ACD CPR，以确保在每个胸部之后发生至关重要的全胸后坐。在2期结果的基础上，2期继续研究正在进行，以获得足够的临床数据，以获得ITD和ACD CPR的监管批准，作为一种旨在改善出院率和心脏骤停后30天神经完整存活的技术。目前正在申请资金，以完成一项关键性的SBIR 2期延续研究，比较sCPR与ACD CPR + ITD，该研究设计为一项前瞻性、随机、1400名患者、6个地点的临床试验。出院时神经功能良好是主要终点，幸存者将被随访长达一年。仅在美国，就有40万人因心脏骤停而在院外死亡，这项技术的广泛应用每年可能会导致超过5万名神经系统完好的幸存者。这项SBIR 2期持续研究主要是为了获得足够的临床数据，以获得阻抗阈值装置（ITD, ResQPOD.）和主动压缩减压CPR装置（ACD CPR, ResQPump.）组合的监管许可，作为一种旨在提高心脏骤停后30天完整神经系统存活的技术。提出了一项关键性临床试验，以前瞻性、随机、1400例患者、6点临床试验的形式，确定使用ITD并确保ACD CPR与单独sCPR相比具有完整神经功能的30天生存率。如果这个项目成功，新的复苏系统有可能使美国每年40万例院外心脏性猝死患者中的5万多例患者复苏。

DESCRIPTION (provided by applicant): Despite the widespread practice of basic and advanced life support, over 1000 patients die each day in the United States from an out-of-hospital cardiac arrest. Even though they receive standard cardiopulmonary resuscitation (sCPR) the average national survival to hospital discharge for these patients remains <5%. The applicants have developed two new CPR devices, the inspiratory impedance threshold device (ITD) and an active compression decompression (ACD) CPR device that together quadruple blood flow to the heart and brain when used in combination and compared with sCPR. The ITD is the size of a child's fist and it is attached to the airway via a face mask or breathing tube. The ACD CPR is a hand-held device that compresses the chest like a pair of hands but facilitates active and full chest wall recoil as it has a suction cup that attaches to the chest. These devices work synergistically by increasing the extent and duration of negative intrathoracic pressure or intrathoracic vacuum during the chest wall recoil phase of sCPR, thereby more effectively refilling the heart after each chest compression. The Phase 2 clinical trial, which was focused only on the ITD + sCPR, demonstrated that intensive care unit admission rate (primary study endpoint) in patients with an initial heart rhythm of pulseless electrical activity increased from 19% to 52% (p=0.02). The Phase 2 research further lead to the discovery that during sCPR ventilation rates and duration are often excessive and that the chest is often not allowed to fully recoil after each compression. Each of these common clinical errors was electronically recorded for the first time and then shown to be detrimental, if not deadly, in follow-up animal studies on cardiac arrest. Based upon these Phase 2 results the applicants improved the ITD by adding a ventilation timing light to guide proper ventilation and added ACD CPR to the study design to assure that the critically important full chest recoil occurs after each chest. Building upon the Phase 2 results, the Phase 2 Continuation research is being conducted to obtain sufficient clinical data for regulatory clearance for the ITD and ACD CPR as a technology intended to improve hospital discharge and 30 day neurologically-intact survival after cardiac arrest. Funding is being request to complete a pivotal SBIR Phase 2 Continuation study comparing sCPR versus ACD CPR + the ITD designed as a prospective, randomized, 1400 patient, 6-site clinical trial. Hospital discharge with good neurological function is the primary endpoint and survivors will be followed for up to one year. With 400,000 out-of-hospital deaths from cardiac arrest in the United States alone, widespread application of this technology could result in more than 50,000 neurologically-intact survivors per year. PUBLIC HEALTH RELEVANCE This SBIR Phase 2 Continuation research is primarily intended to obtain sufficient clinical data for regulatory clearance for the combination of an impedance threshold device (ITD, ResQPOD.) and an active compression decompression CPR device (ACD CPR, ResQPump.) as a technology intended to improve 30 day intact neurological survival after cardiac arrest. A pivotal clinical trial is proposed in the form of a prospective, randomized, 1400 patient, six-site clinical trial to determine the 30 day survival rate with intact neurologic function when using the ITD and assuring full chest wall recoil with ACD CPR compared to sCPR alone. If this program is successful, the new resuscitation system has the potential to resuscitate approximately 50,000 more patients of the 400,000 sudden cardiac deaths that occur outside the hospital each year in the United States.