Therapeutic Plasma Exchange in Resistant Cytokine Storm of COVID 19
- Conditions
- COVID 19
- Interventions
- Procedure: Therapeutic Plasma Exchange (TPE)
- Registration Number
- NCT04457349
- Lead Sponsor
- Alexandria University
- Brief Summary
This research is planned to illustrate the efficacy of Therapeutic Plasma Exchange (TPE) treatment in COVID-19 patients with resistant cytokine storm state.
- Detailed Description
In early December 2019, several pneumonia cases of unknown origin were observed in Wuhan (China). A novel enveloped RNA β coronavirus was isolated and named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The new virus rapidly spread across China and worldwide. On March 11th 2020, the World Health Organization (WHO) declared coronavirus disease 2019 (COVID-19) a pandemic. As of 19June 2020, COVID-19 has been confirmed in 8,385,440 individuals globally with deaths reaching 450,686 with a morality of 5.37%. Egypt has 50,437 confirmed cases and 1938 deaths.
The virus mainly spreads through respiratory droplets from infected patients.The clinical spectrum of COVID-19 infection ranges from asymptomatic forms to severe pneumonia requiring hospitalization and isolation in critical care units with the need of mechanical ventilation due to acute respiratory distress syndrome (ARDS). Main symptoms include fever, fatigue and dry cough. Common laboratory findings include lymphopenia and elevated lactate dehydrogenase levels. Platelet count is usually normal or mildly decreased. C reactive protein (CRP) and erythrocyte sedimentation rate are usually increased while procalcitonin levels are normal and elevation of procalcitonin usually indicates secondary bacterial infection. Ferritin, D-dimer, and creatine kinase elevation is associated with severe disease. Chest computed tomographic scans show a typical pattern of bilateral patchy shadows or ground glass opacity.
Severe COVID-19 conditions are usually due to an aggressive inflammatory response known as "cytokine storm" that is characterized by the release of a large amount of pro-inflammatory cytokines. Lung injury, multiorgan failure, and unfavorable prognosis of severe COVID-19 infection have been attributed mainly to the cytokine storm state.
Many proinflammatory cytokines elevate in COVID-19 patients including IL-1, IL-6, IL-8, IL-10, tumour necrosis factor α (TNF-α) and interferon Ȣ(IFN-Ȣ) stimulating immune cells to invade sites of infection causing endothelial dysfunction, vascular damage, alveolar damage and ARDS. Cytokine storm has been reported in several viral infections including influenza H5N1 virus, influenza H1N1 virus, and the two coronaviruses highly related to COVID-19; "SARS-CoV" and "MERS-CoV".
Therapeutic approaches to manage the COVID-19 cytokine storm might provide an avenue to decrease the COVID-19 associated morbidity and mortality. Options include immunomodulators, cytokine antagonists and cytokine removal. Tocilizumab (IL-6 antagonist), Anakinra (antagonist of IL-1 β), TNF blockers, ruxolitinib (JAK1/2 inhibitor ), corticosteroids, intravenous immunoglobulins and therapeutic plasma exchange (TPE) have been used with variable efficacy.
Therapeutic plasma exchange can remove inflammatory factors, block the "cytokine storm", to reduce the damage of inflammatory response to the body. This therapy can be used for severe and critical patients in the early and middle stages of the disease. Patel and colleagues utilized TPE during the 2009 H1N1 influenza A outbreak in three pediatric patients presenting in a similar fashion to those seen with fulminant COVID-19 today. All three had full recovery from their illness after receiving rescue TPE. Adeli at al. used TPE as a rescue therapy in patients with severe forms of COVID-19 ( septic shock, ARDS ) with very good results. Out of 8 patients, 7 patients improved and one patient died. Zhang et al. also tried TPE in three COVID-19 patients who despite receiving antiviral treatment developed respiratory distress and levels of IL-6 increased rapidly. All patients improved clinically and radiologically with negative nucleic acid testing and were discharged 10-14 days later.
In Egypt, the first line drug to treat cytokine storm of COVID-19 is tocilizumab with good results. But a considerable percentage of patients do not respond to it leaving physicians with very limited options and usually patients deteriorated rapidly with high mortality. Based on the encouraging results of TPE in severe COVID-19 infections and the familiarity of the procedure, TPE could be a good option in those patients who do not respond to tocilizumab.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 10
-
COVID-19 positive patients (confirmed by PCR) with cytokine storm state who will not improve after two doses of tocilizumab.
-
Criteria of failure (resistance) to tocilizumab:
- Persistent high IL-6 and CRP.
- Persistent worsening of respiratory symptoms ( dyspnea, tachypnea, increased oxygen (O2) requirements or even need for mechanical ventilation).
- Partial arterial pressure of oxygen to fractional inspired concentration of oxygen (PaO2/FiO2) ratio < 150.
- Persistent fever (˃38.5°C) despite normal procalcitonin level.
-
- Refractory septic shock:
( It is defined according to surviving sepsis campaign as the presence of hypotension with end organ dysfunction requiring high dose vasopressor support often greater than 0.5 µg/kg/min norepinephrine or equivalent).
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Therapeutic Plasma Exchange (TPE) Therapeutic Plasma Exchange (TPE) Each patient will undergo two sessions. TPE will be done through filtration technique using a plasma filter at a dose of (1-1.5) plasma volume/session. Fresh frozen plasma or albumin 5% will be used to replace plasma.
- Primary Outcome Measures
Name Time Method mortality 28 day Number of patients deaths of the total of patients included
- Secondary Outcome Measures
Name Time Method the mean time with Non-invasive mechanical ventilation through study completion, and average of 1 month to calculate the mean time with Non-invasive mechanical ventilation
the mean time of intubation through study completion, and average of 1 month to calculate the mean time of intubation
levels of ferritin through study completion, and average of 1 month To evaluate the effect of TPE on the serum levels of inflammatory markers
Incidence of adverse events through study completion, and average of 1 month To calculate the number of adverse events in patients with COVID-19 treated with TPE
time to reverse-transcriptase polymerase chain reaction (RT-PCR) virus negativity through study completion, and average of 1 month To evaluate the time to RT-PCR virus negativity
the levels of CRP through study completion, and average of 1 month To evaluate the effect of TPE on the serum levels of inflammatory markers
the mean time with oxygen therapy through study completion, and average of 1 month to calculate the mean time with oxygen therapy
respiratory function parameters through study completion, and average of 1 month To calculate the mean of levels of oxygen saturation
the requirement of additional organ support through study completion, and average of 1 month Percentage of patients with dialysis
the levels of IL-6 through study completion, and average of 1 month To evaluate the effect of TPE on the serum levels of inflammatory markers
radiological lung extension through study completion, and average of 1 month to evaluate the lung extension of pneumonia
mean duration of hospitalization and ICU use through study completion, and average of 1 month Days of hospitalization in survivors and/or days at ICU throughout the study
the levels of procalcitonin (PCT) through study completion, and average of 1 month To evaluate the effect of TPE on the serum levels of inflammatory markers
levels of D-dimer through study completion, and average of 1 month To evaluate the effect of TPE on the serum levels of inflammatory markers
Trial Locations
- Locations (1)
Faculty of Medicine, Alexandria university, Egypt
🇪🇬Alexandria, Egypt