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

Abstract: Multiple organ failure (MOF) is a common cause of morbidity and mortality for individuals in the intensive careunit (ICU) including those suffering from COVID-19. Prevention of multiorgan injury and subsequent treatmentshould be a focus in the ICU, and is thought to be especially important in supportive care of critically ill patientsand COVID-19 patients. In efforts to prevent and treat MOF, the gut may be a key target as it is a driver of MOFdevelopment. 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 responseinitiating systemicinflammatory response syndrome (SIRS)leading to MOF. A novel treatment may be direct peritonealresuscitation (DPR), which consists of circulating commercially available peritoneal dialysis solution throughoutthe peritoneal cavity. DPR improves tissue perfusion and reduces cellular ischemia. In turn, DPR has beenextensively proven to attenuate SIRS, increase blood flow in end-organs with corresponding decreased injuryand improve survival in preclinical small animal models of hemorrhagic shock (HS). Further, significant clinicalbenefits of DPR have been demonstrated in 1) improved recovery of patients requiring surgical management ofabdominal catastrophe (trauma, sepsis and necrotizing enterocolitis) and 2) significantly increased numbers oforgans transplanted from brain dead, heart beating donors. However, the risk of injury-related complicationsduring peritoneal access is a substantial roadblock to the clinical utility of DPR, especially for unstable, criticallyill patients, who require peritoneal catheter placement to be quick, safe and conducted at the bedside. To bringthe benefits of DPR to the ICU, TheraNova has developed the Multi-Organ Failure Treatment (MOFT). MOFThas 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 havedemonstrated 1) attenuated risk of tissue injury, 2) timely peritoneal access, 3) evidence-based insertionguidance, and 4) consistent, autonomous peritoneal lavage. The goal of this revision application is to validateMOFT in a clinically relevant and reproducible animal model before translation to clinical use. First, we willenhance device utility by optimizing the MOFT PAS controller to enable three modalities of evidence-basedguidance within a centralized hub (Aim 1). We will then conduct a randomized, controlled study with an HS swinemodel to demonstrate safe and effective peritoneal access (Aim 2.1) and DPR treatment for the prevention ofgut-derived systemic inflammation and organ injury (Aim 2.2). Successful completion of this proposed effort willprovide sufficient evidence to file for an Investigational Device Exemption with the FDA. We will then initiate pilotclinical studies in the ICU and focus specifically on critically-ill patients with COVID-19.