A Device for the Prevention and Treatment of Multiple Organ Failure in COVID-19 Patients

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Abstract Multiple organ failure (MOF) is a common cause of morbidity and mortality for individuals in the intensive care unit (ICU) including those suffering from COVID-19. Prevention of multiorgan injury and subsequent treatment should be a focus in the ICU, and is thought to be especially important in supportive care of critically ill patients and COVID-19 patients. In efforts to prevent and treat MOF, the gut may be a key target as it is a driver of MOF development. Specifically, critical illness has the potential to compromise gut perfusion in many patients (including those with embolic or shock insult), which can propel a pathological response initiating systemic inflammatory response syndrome (SIRS) leading to MOF. A novel treatment may be direct peritoneal resuscitation (DPR), which consists of circulating commercially available peritoneal dialysis solution throughout the peritoneal cavity. DPR improves tissue perfusion and reduces cellular ischemia. In turn, DPR has been extensively proven to attenuate SIRS, increase blood flow in end-organs with corresponding decreased injury and improve survival in preclinical small animal models of hemorrhagic shock (HS). Further, significant clinical benefits of DPR have been demonstrated in 1) improved recovery of patients requiring surgical management of abdominal catastrophe (trauma, sepsis and necrotizing enterocolitis) and 2) significantly increased numbers of organs transplanted from brain dead, heart beating donors. However, the risk of injury-related complications during peritoneal access is a substantial roadblock to the clinical utility of DPR, especially for unstable, critically ill patients, who require peritoneal catheter placement to be quick, safe and conducted at the bedside. To bring the benefits of DPR to the ICU, TheraNova has developed the Multi-Organ Failure Treatment (MOFT). MOFT has two functions: 1) safe, quick bedside access through the use of a proprietary Peritoneal Access System (PAS), and 2) autonomous DPR through the use of a Lavage Controller (LC). In our preliminary work, we have demonstrated 1) attenuated risk of tissue injury, 2) timely peritoneal access, 3) evidence-based insertion guidance, and 4) consistent, autonomous peritoneal lavage. The goal of this revision application is to validate MOFT in a clinically relevant and reproducible animal model before translation to clinical use. First, we will enhance device utility by optimizing the MOFT PAS controller to enable three modalities of evidence-based guidance within a centralized hub (Aim 1). We will then conduct a randomized, controlled study with an HS swine model to demonstrate safe and effective peritoneal access (Aim 2.1) and DPR treatment for the prevention of gut-derived systemic inflammation and organ injury (Aim 2.2). Successful completion of this proposed effort will provide sufficient evidence to file for an Investigational Device Exemption with the FDA. We will then initiate pilot clinical studies in the ICU and focus specifically on critically-ill patients with COVID-19.