Sutureless Laparoscopic Partial Nephrectomy Using Laser Tissue Welding: Preclinic

使用激光组织焊接进行无缝腹腔镜肾部分切除术：临床前

• 批准号: 8528580
• 负责人: GILAD E AMIEL
• 金额: $ 84.43万
• 依托单位: LASER TISSUE WELDING, INC.
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-08-10 至 2015-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8528580
• 关键词: Abdomen; Abdominal Abscess; Ablation; Accounting; Address; Adverse event; Aftercare; Albumins; Animals; Anticoagulation; Area; Benign; Bile fluid; Biocompatible Materials; Biological Preservation; Blood; Blood Coagulation Disorders; Burn injury; Caliber; Cerebrospinal Fluid; Clinical; Clinical Research; Clinical Trials; Coagulation Process; Complex; Control Groups; Creatinine clearance measurement; Defect; Device Safety; Devices; Diagnosis; Domestic Pig; Drug resistance; Environment; Esophageal; Evaluation; Excision; Extravasation; Family suidae; Fiber Optics; Fistula; Frequencies; Goals; Government; Grant; Guidelines; Healed; Hematoma; Hemorrhage; Hemostatic Agents; Hemostatic function; Histologic; Hospital Costs; Hospitals; Human; Hypospadias; Image; In Vitro; Incidence; Institutional Review Boards; Kidney; Kidney Neoplasms; Lasers; Length; Length of Stay; Lesion; Life; Liquid substance; Liver; Liver neoplasms; Lymph; Malignant - descriptor; Marketing; Mediating; Medical; Medicine; Methods; Morbidity - disease rate; Necrosis; Neoplasms; Nephrectomy; Nephrons; Newly Diagnosed; Normal tissue morphology; Nuclear; Operative Surgical Procedures; Optics; Organ; Organ Donor; Outcome; Pancreas; Patients; Perforation; Persons; Phase; Postoperative Hemorrhage; Postoperative Period; Prevalence; Procedures; Pseudomonas aeruginosa; Randomized; Renal Cell Carcinoma; Renal Mass; Renal carcinoma; Renal function; Renal pelvis; Resected; Robotics; Safety; Scanning; Septicemia; Small Business Innovation Research Grant; Solid; Spinal Cord; Spinal nerve structure; Spleen; Staging; Sterility; Sterilization; Streptococcus pyogenes; Study Subject; Surface; Surgeon; Surgical sutures; Technology; Testing; Therapeutic Effect; Time; Tissues; Toxic effect; Toxicology; Transfusion; Trauma; United States; Urethra; Urethral Diverticulum; Urethral Stricture; Urine; Vascular blood supply; Visceral; Warm Ischemia; Welding; base; biomaterial compatibility; blood product; cancer transplantation; college; commercial application; gastrointestinal; healing; improved; in vivo; innovation; liver repair; liver transplantation; methicillin resistant Staphylococcus aureus; migration; minimally invasive; mortality; novel; pre-clinical; preclinical efficacy; preclinical safety; pressure; prevent; prospective; prototype; public health relevance; radiofrequency; reconstruction; renal artery; repaired; response; scaffold; seal; secondary infection; success; tissue repair; tissue support frame; tissue trauma; tissue welding; tumor; urinary

DESCRIPTION (provided by applicant): Preservation of functioning renal parenchyma is important and nephron-sparing surgery substitutes for radical nephrectomy in appropriately selected patients with renal cell carcinoma. Laparoscopic partial nephrectomy (LPN) has demonstrated excellent outcomes in terms of oncologic control, but is under-used due to major technical challenges of parenchymal hemostasis, pelvi-caliceal reconstruction, parenchymal renorrhaphy, bleeding and prolonged warm ischemia. Laser Tissue Welding, Inc. (LTW) uses a non-compressive, non-ablative technology to join and seal tissues for controlling the leakage of blood, gastrointestinal fluids, urine, bile, lymph, and cerebrospinal fluid. It is life saving when used on the surfaces of solid visceral organs, such as the liver spleen, pancreas and kidney, involved in trauma, cancer and transplantation in presence of coagulopathies or anticoagulation. Preclinical in vivo chronic4, 6 animal studies and with a phase I SBIR prototype manufacturing of characterized and validated biomaterials was completed. Under a phase II SBIR our company has commenced human clinical trials for the liver resections under a FDA IDE approval. Fast Track Phase I: Specific Aims* (Time: 6 months) 1. Laparoscopic partial nephrectomy using laser tissue welding combination device: Eight week preclinical safety and efficacy studies in 12 pigs. The purpose of this study is to evaluate biocompatibility and toxicity for performing the laser tissue welding procedure applied to the kidney of domestic pigs after laparoscopic partial nephrectomy. Twelve pigs will be randomly assigned to two groups of 6 pigs each (control and treatment). Both the control group and the treatment group will have temporary occlusion of the organ's blood supply for ten minutes and will undergo a partial nephrectomy. The study group will undergo tissue welding and the control group partial nephrectomy without additional treatment. All animals will be terminated at 8 weeks. 2. Investigational device exemption submission and approval. 3. IRB approval Fast Track Phase II Specific Aims* (Time: 24 months) Laparoscopic partial nephrectomy using laser tissue welding device: Safety and Efficacy Clinical Trial. 1. Pilot human feasibility clinical study in 10 patient. 2. Pivotal one center prospective randomized clinical study randomized to 20 test subjects and 20 controls. These are actual patients undergoing robotically assisted laparoscopic resection of T1A (<4cm) renal tumors. All subjects will undergo occlusion of the renal artery and resection of the tumor. The study group will undergo tissue welding and the control group conventional suturing of the defect. Safety will be assessed by tabulating the frequency of adverse events, such as 30 day postoperative morbidity due to a) secondary infection, intra-abdominal abscess formation and septicemia, b) late bleeding or secondary hemorrhage or hematoma; c) urine leak; d) damage to the kidney parenchyma evident by compromised renal function or long term renal function via creatinine clearance and MAG3 nuclear renal scan and e) mortality. Efficacy will be determined by comparing treatment and controls with respect to the objective response rate based on the number of patients who achieve a) complete hemostasis; b) Renal artery clamp time required to achieve hemostasis; c) intraoperative and postoperative blood loss; d) blood product transfusions; e) operative time; f) ICU stay; g) hospital stay and f) total hospital costs. Technology innovation: LTW using our propriety biomaterials is an enhanced surgical ability that enables hemostatic sealing of tissues accurately and instantly without compression, ablation or thermal damage, thus enabling surgical interventions not deemed possible before. These unmet clinical needs are sealing of solid visceral organs (liver, kidney, pancreas and spleen) involved in polytrauma, and neoplasms; spinal cord and nerve reattachment; sterilization of contaminated wounds, sealing of dural, esophageal and duodenal perforations; and providing a scaffold for tissue ingrowth. Anticipated Outcomes: Submission of a single pre-market market approval (PMA) application with separate IDE applications for each anatomical region. Potential commercial applications: LTW may be used to sealing and joining all tissues. Applications include liver trauma repair and after resection for primary and metastatic liver tumors; split liver transplants doubling donor organ pool; partial nephrectomy for benign and malignant lesions; urethral repair: for hypospadias, urethral stricture, urethral diverticulum, and urethral fistulae and all surgical procedures that currently use sutures.

描述（由申请人提供）：保留功能性肾实质很重要，在适当选择的肾细胞癌患者中，保留肾单位手术可替代根治性肾切除术。腹腔镜肾部分切除术（LPN）在肿瘤控制方面已显示出良好的结局，但由于实质止血、肾盂盏重建、实质肾缝合、出血和长时间热缺血等主要技术挑战而未得到充分使用。激光组织焊接公司(LTW)使用非压缩、非消融技术连接和密封组织，以控制血液、胃肠液、尿液、胆汁、淋巴液和脑脊液的泄漏。这是拯救生命， 用于涉及创伤、癌症和存在凝血病或抗凝作用的移植的固体内脏器官表面，如肝脏、脾脏、胰腺和肾脏。完成了临床前体内长期4、6动物研究以及表征和验证生物材料的I期SBIR原型制造。在第二阶段SBIR下，我们公司已开始在FDA IDE批准下进行肝脏切除的人体临床试验。快速通道第一阶段：具体目标 *（时间：6个月）1.使用激光组织焊接组合器械的腹腔镜肾部分切除术：在12头猪中进行的8周临床前安全性和有效性研究。本研究旨在评价生物相容性和毒性 用于在腹腔镜肾部分切除术后对家猪的肾脏进行激光组织焊接手术。将12头猪随机分配至两组，每组6头猪（对照组和给药组）。对照组和治疗组都将暂时阻断器官的血液供应10分钟，并进行肾部分切除术。研究组行组织焊接术，对照组行肾部分切除术，不做其他处理。所有动物将在第8周处死。2.试验用器械豁免提交和批准。3. IRB批准快速通道II期特定目标 *（时间：24个月）使用激光组织焊接器械的腹腔镜肾部分切除术：安全性和有效性临床试验。1.在10名患者中进行的初步人体可行性临床研究。2.首次单中心前瞻性随机临床研究，随机分为20例受试者和20例对照。这些是接受机器人辅助腹腔镜T1 A（<4cm）肾肿瘤切除术的实际患者。所有受试者将接受肾动脉闭塞和肿瘤切除。研究组采用组织焊接法修复缺损，对照组采用传统的组织焊接法修复缺损.将通过对不良事件的频率进行制表来评估安全性，如术后30天的发病率，原因如下：a）继发性感染、腹腔内脓肿形成和败血症，B）晚期出血或继发性出血或血肿; c）尿漏; d）肾实质损伤，通过肌酐清除率和MAG 3核肾扫描显示肾功能受损或长期肾功能，以及e）死亡。将通过比较治疗组和对照组的客观缓解率来确定疗效，客观缓解率基于实现a）完全止血; B）实现止血所需的肾动脉钳夹时间; c）术中和术后失血量; d）血液制品输注; e）手术时间; f）ICU住院时间; g）住院时间和f）总住院费用的患者数量。技术创新：使用我们专有生物材料的LTW是一种增强的外科手术能力，能够准确、即时地对组织进行止血凝闭，而不会造成压迫、消融或热损伤，从而实现以前认为不可能的外科手术干预。这些未满足的临床需求是涉及多发性创伤和肿瘤的实体内脏器官（肝、肾、胰腺和脾）的密封;脊髓和神经重新附着;污染伤口的灭菌，硬脑膜、食管和十二指肠穿孔的密封;以及为组织向内生长提供支架。预期结局：提交单个上市前批准（PMA）申请，并为每个解剖区域提交单独的IDE申请。潜在的商业应用：LTW可用于密封和连接所有组织。应用包括肝创伤修复和原发性和转移性肝肿瘤切除术后;劈离式肝移植使供体器官库加倍;良性和恶性病变的部分肾切除术;尿道修复：尿道下裂、尿道狭窄、尿道憩室和 尿道瘘和目前使用缝线的所有外科手术。