Exploratory study on the efficacy and safety of direct hemoperfusion using polymyxin B-immobilized polystyrene column (PMX-DHP), for COVID-19 patients (X-code): Method/Study design (Preprint)

Abstract

polymyxin B-immobilized fiber column (PMX, Toraymyxin column) was approved for the relief of SIRS (systemic inflammatory response syndrome) caused by bacterial infection or endotoxemia. PMX reduces lung damage by removing leukocytes and cytokines in addition to endotoxin removal, in the setting of idiopathic pulmonary fibrosis. Acute exacerbation of interstitial pneumonia pathologically presents with diffuse alveolar damage (DAD). PMX direct hemoperfusion (PMX-DHP) demonstrated efficacy, improving oxygenation. SARS-CoV-2 virus causes COVID-19 pneumonia that emerged in December 2019. The condition may become severe about 1 week after onset, and respiratory failure rapidly develops, requiring intensive care management. A characteristic of COVID-19-related severe pneumonia is ground-glass opacities rapidly progressing in both lungs, which subsequently turn into infiltrative shadows. This condition could be classified as DAD. As for the congealing fibrinogenolysis system, D-dimer, fibrin/fibrinogen degradation product quantity and prolonged prothrombin time were significant factors in non-surviving COVID-19 cases, associated with aggravated pneumonia. Clinical trials are being conducted but, with the exception of remdesivir and dexamethasone, no treatments have yet been approved. COVID-19 aggravates with the deterioration of oxygen saturation, decrease in lymphocytes and the occurrence of an abnormal congealing fibrinogenolysis system, leading to diffuse lung damage. Once the condition transitions from moderate to severe, it is most necessary to prevent further exacerbation by providing treatment what will suppress the above symptoms as soon as possible.

to acquire treatment options to prevent the transition from acute exacerbation of interstitial pneumonia to DAD. The mechanism of action envisioned for PMX-DHP is to reduce congealing fibrinogenolysis system abnormalities and increase oxygenation by removing activated leucocytes and cytokines, which are risk factors for the aggravation of COVID-19-related pneumonia.

we will conduct a multicenter prospective intervention single-group study to evaluate the efficacy and safety of direct hemoperfusion using PMX-DHP for COVID-19 patients. Efficacy will be evaluated by the primary endpoint, which is the rate of Ordinal Scale for Clinical Improvement after PMX-DHP of at least 1 point from a status of 4.5.6 on Day 15. The effect of PMX-DHP will be estimated by setting a control group with background factors from non-PMX-DHP patients enrolled in the COVID-19 registry. This study will be carried out as a single-group open-label study and will be compared with a historical control. The historical control will be selected from the COVID-19 registry according to age, gender, and severity of pneumonia.

this study will help determine PMX-DHP treatment options in the medical setting by quickly collecting and publishing information on patient background and on the efficacy and safety of treatment by PMX-DHP.

from a clinical perspective, PMX-DHP is expected to become a first-line therapy to address unmet medical needs and prevent the exacerbation from moderate to severe ARDS in COVID-19 cases.