Efficacy and Safety of Direct Hemoperfusion Using Polymyxin B-Immobilized Polystyrene Column for Patients With COVID-19: Protocol for an Exploratory Study
BackgroundPolymyxin B-immobilized fiber column (PMX; Toraymyxin column) was approved for the relief of systemic inflammatory response syndrome caused by bacterial infection or endotoxemia. PMX reduces lung damage by removing leukocytes and cytokines in addition to endotoxin r...
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| Format: | Article |
| Language: | English |
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JMIR Publications
2022-11-01
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| Series: | JMIR Research Protocols |
| Online Access: | https://www.researchprotocols.org/2022/11/e37426 |
| _version_ | 1827857850051854336 |
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| author | Junko Terada-Hirashima Shinyu Izumi Daisuke Katagiri Yukari Uemura Ayako Mikami Wataru Sugiura Shinji Abe Arata Azuma Haruhito Sugiyama |
| author_facet | Junko Terada-Hirashima Shinyu Izumi Daisuke Katagiri Yukari Uemura Ayako Mikami Wataru Sugiura Shinji Abe Arata Azuma Haruhito Sugiyama |
| author_sort | Junko Terada-Hirashima |
| collection | DOAJ |
| description |
BackgroundPolymyxin B-immobilized fiber column (PMX; Toraymyxin column) was approved for the relief of 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. The SARS-CoV-2 virus causes COVID-19, which 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 nonsurviving COVID-19 cases, associated with aggravated pneumonia. Clinical trials are being conducted, but except for 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 necessary to prevent further exacerbation by providing treatment that will suppress the aforementioned symptoms as soon as possible.
ObjectiveThis study aims to access 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 leukocytes and cytokines, which are risk factors for the aggravation of COVID-19–related pneumonia.
MethodsWe will conduct a multicenter, prospective, intervention, single-group study to evaluate the efficacy and safety of direct hemoperfusion using PMX-DHP for patients with COVID-19. Efficacy will be evaluated by the primary end point, which is the rate of Ordinal Scale for Clinical Improvement after PMX-DHP of at least 1 point from a status of 4, 5, or 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.
ResultsThe study period is scheduled from September 28, 2020, through April 30, 2023. Patient enrollment was scheduled from the Japan Registry of Clinical Trials publication for March 31, 2022. Data fixation is scheduled for October 2022, with the publication of the results by March 2023.
ConclusionsFrom a clinical perspective, PMX-DHP is expected to become an adjunctive therapy to address unmet medical needs and prevent the exacerbation from moderate to severe acute respiratory distress syndrome in COVID-19 cases.
International Registered Report Identifier (IRRID)DERR1-10.2196/37426 |
| first_indexed | 2024-03-12T12:46:15Z |
| format | Article |
| id | doaj.art-403d709f3a654d80a6bd6d4127742ef0 |
| institution | Directory Open Access Journal |
| issn | 1929-0748 |
| language | English |
| last_indexed | 2024-03-12T12:46:15Z |
| publishDate | 2022-11-01 |
| publisher | JMIR Publications |
| record_format | Article |
| series | JMIR Research Protocols |
| spelling | doaj.art-403d709f3a654d80a6bd6d4127742ef02023-08-28T23:17:21ZengJMIR PublicationsJMIR Research Protocols1929-07482022-11-011111e3742610.2196/37426Efficacy and Safety of Direct Hemoperfusion Using Polymyxin B-Immobilized Polystyrene Column for Patients With COVID-19: Protocol for an Exploratory StudyJunko Terada-Hirashimahttps://orcid.org/0000-0002-1437-5896Shinyu Izumihttps://orcid.org/0000-0002-6384-5022Daisuke Katagirihttps://orcid.org/0000-0003-1395-2644Yukari Uemurahttps://orcid.org/0000-0002-3013-7775Ayako Mikamihttps://orcid.org/0000-0001-8124-8216Wataru Sugiurahttps://orcid.org/0000-0002-3132-0918Shinji Abehttps://orcid.org/0000-0003-0949-4601Arata Azumahttps://orcid.org/0000-0003-0506-9966Haruhito Sugiyamahttps://orcid.org/0000-0002-7849-1327 BackgroundPolymyxin B-immobilized fiber column (PMX; Toraymyxin column) was approved for the relief of 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. The SARS-CoV-2 virus causes COVID-19, which 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 nonsurviving COVID-19 cases, associated with aggravated pneumonia. Clinical trials are being conducted, but except for 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 necessary to prevent further exacerbation by providing treatment that will suppress the aforementioned symptoms as soon as possible. ObjectiveThis study aims to access 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 leukocytes and cytokines, which are risk factors for the aggravation of COVID-19–related pneumonia. MethodsWe will conduct a multicenter, prospective, intervention, single-group study to evaluate the efficacy and safety of direct hemoperfusion using PMX-DHP for patients with COVID-19. Efficacy will be evaluated by the primary end point, which is the rate of Ordinal Scale for Clinical Improvement after PMX-DHP of at least 1 point from a status of 4, 5, or 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. ResultsThe study period is scheduled from September 28, 2020, through April 30, 2023. Patient enrollment was scheduled from the Japan Registry of Clinical Trials publication for March 31, 2022. Data fixation is scheduled for October 2022, with the publication of the results by March 2023. ConclusionsFrom a clinical perspective, PMX-DHP is expected to become an adjunctive therapy to address unmet medical needs and prevent the exacerbation from moderate to severe acute respiratory distress syndrome in COVID-19 cases. International Registered Report Identifier (IRRID)DERR1-10.2196/37426https://www.researchprotocols.org/2022/11/e37426 |
| spellingShingle | Junko Terada-Hirashima Shinyu Izumi Daisuke Katagiri Yukari Uemura Ayako Mikami Wataru Sugiura Shinji Abe Arata Azuma Haruhito Sugiyama Efficacy and Safety of Direct Hemoperfusion Using Polymyxin B-Immobilized Polystyrene Column for Patients With COVID-19: Protocol for an Exploratory Study JMIR Research Protocols |
| title | Efficacy and Safety of Direct Hemoperfusion Using Polymyxin B-Immobilized Polystyrene Column for Patients With COVID-19: Protocol for an Exploratory Study |
| title_full | Efficacy and Safety of Direct Hemoperfusion Using Polymyxin B-Immobilized Polystyrene Column for Patients With COVID-19: Protocol for an Exploratory Study |
| title_fullStr | Efficacy and Safety of Direct Hemoperfusion Using Polymyxin B-Immobilized Polystyrene Column for Patients With COVID-19: Protocol for an Exploratory Study |
| title_full_unstemmed | Efficacy and Safety of Direct Hemoperfusion Using Polymyxin B-Immobilized Polystyrene Column for Patients With COVID-19: Protocol for an Exploratory Study |
| title_short | Efficacy and Safety of Direct Hemoperfusion Using Polymyxin B-Immobilized Polystyrene Column for Patients With COVID-19: Protocol for an Exploratory Study |
| title_sort | efficacy and safety of direct hemoperfusion using polymyxin b immobilized polystyrene column for patients with covid 19 protocol for an exploratory study |
| url | https://www.researchprotocols.org/2022/11/e37426 |
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