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Therapeutic Plasma Exchange in Resistant Cytokine Storm of COVID 19

Primary Purpose

COVID 19

Status

Completed

Phase

Not Applicable

Locations

Egypt

Study Type

Interventional

Intervention

Therapeutic Plasma Exchange (TPE)

About this trial

This is an interventional treatment trial for COVID 19

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

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:
  1. Persistent high IL-6 and CRP.
  2. Persistent worsening of respiratory symptoms ( dyspnea, tachypnea, increased oxygen (O2) requirements or even need for mechanical ventilation).
  3. Partial arterial pressure of oxygen to fractional inspired concentration of oxygen (PaO2/FiO2) ratio < 150.
  4. Persistent fever (˃38.5°C) despite normal procalcitonin level.

Exclusion Criteria:

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).

Sites / Locations

Faculty of Medicine, Alexandria university, Egypt

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Therapeutic Plasma Exchange (TPE)

Arm Description

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.

Outcomes

Primary Outcome Measures

mortality

Number of patients deaths of the total of patients included

Secondary Outcome Measures

the mean time with oxygen therapy

to calculate the mean time with oxygen therapy

the mean time with Non-invasive mechanical ventilation

to calculate the mean time with Non-invasive mechanical ventilation

the mean time of intubation

to calculate the mean time of intubation

respiratory function parameters

To calculate the mean of PaO2/FiO2

respiratory function parameters

To calculate the mean of levels of oxygen saturation

radiological lung extension

to evaluate the lung extension of pneumonia

mean duration of hospitalization and ICU use

Days of hospitalization in survivors and/or days at ICU throughout the study

the requirement of additional organ support

Percentage of patients with dialysis

the levels of IL-6

To evaluate the effect of TPE on the serum levels of inflammatory markers

Incidence of adverse events

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

To evaluate the time to RT-PCR virus negativity

the levels of CRP

To evaluate the effect of TPE on the serum levels of inflammatory markers

the levels of procalcitonin (PCT)

To evaluate the effect of TPE on the serum levels of inflammatory markers

levels of D-dimer

To evaluate the effect of TPE on the serum levels of inflammatory markers

levels of ferritin

To evaluate the effect of TPE on the serum levels of inflammatory markers

Full Information

NCT ID

NCT04457349

First Posted

June 30, 2020

Last Updated

April 13, 2022

Sponsor

Alexandria University

1. Study Identification

Unique Protocol Identification Number

NCT04457349

Brief Title

Therapeutic Plasma Exchange in Resistant Cytokine Storm of COVID 19

Official Title

Does Therapeutic Plasma Exchange Have A Role in Resistant Cytokine Storm State Of COVID-19 Infection?

Study Type

Interventional

2. Study Status

Record Verification Date

April 2022

Overall Recruitment Status

Completed

Study Start Date

July 25, 2020 (Actual)

Primary Completion Date

December 29, 2020 (Actual)

Study Completion Date

January 20, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Alexandria University

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

COVID 19

7. Study Design

Primary Purpose

Treatment

Study Phase

Not Applicable

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

10 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Therapeutic Plasma Exchange (TPE)

Arm Type

Experimental

Arm Description

Intervention Type

Procedure

Intervention Name(s)

Therapeutic Plasma Exchange (TPE)

Other Intervention Name(s)

plasmapheresis

Intervention Description

Treatment with Therapeutic Plasma Exchange (TPE)

Primary Outcome Measure Information:

Title

mortality

Description

Number of patients deaths of the total of patients included

Time Frame

28 day

Secondary Outcome Measure Information:

Title

the mean time with oxygen therapy

Description

to calculate the mean time with oxygen therapy

Time Frame