Plasma Exchange in Patients With COVID-19 Disease and Invasive Mechanical Ventilation: a Randomized Controlled Trial

Study Overview
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Brief Summary
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Plasma exchanges with 5% human albumin (2/3 of the exchanged plasma volume) and fresh frozen plasma (FFP: 1/3) in patients with quick <50% or only with 5% albumin in patients with quick of 50% or more. We will exchange between 1.2 and 1.5 plasma volumes, that will vary according to sex, weight, height and hematocrit.

Detailed Description
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Plasma exchange (PE) is a standardized and safe therapeutic procedure, used in the treatment of various diseases that require rapid and prolonged elimination of endogenous and exogenous substances, with deleterious effects on the function of different organs and systems. The efficacy and safety of PE has been demonstrated in patients with fulminant hepatitis (FH), an entity characterized by an exacerbated inflammatory response, multi-organ failure, and high short-term mortality. In FH, plasma exchange improves systemic inflammation, prevents organ failure and renal support requirements, and improves survival. Such treatment eliminates important endogenous and exogenous inducers of the systemic inflammatory response (PAMPs and DAMPs), proinflammatory mediators (cytokines and ROS), and other biologically active substances (nitric oxide, prostaglandins, and bradykinin) that are involved in the pathogenesis of organ failure. Several case reports also suggest that PE is an effective rescue therapy in critically ill patients with influenza A (H1N1). However, the efficacy of PE has not been evaluated in critically ill patients with COVID-19 disease.

Official Title
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Plasma Exchange in Patients With COVID-19 Disease and Invasive Mechanical Ventilation: a Randomized Controlled Trial

Conditions
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Coronavirus

Intervention / Treatment
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* Biological: Plasma exchange
* Drug: Standar medical treatmen


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female subject ≥18 years and < 80 years of age; Subjects with diagnosis of COVID-19 disease by PCR in nasopharyngeal smear, sputum, or bronchial aspirates; Subjects admitted in ICU with invasive mechanical ventilation; Informed consent granted via telephone by relatives or legal representative Exclusion Criteria: More than seven days with invasive mechanical ventilation Refractory Shock (Noradrenaline dose > 0.5 micrograms/ kg/minute) Decompensated Cirrhosis Chronic kidney disease requiring hemodialysis Active neoplastic disease Severe chronic heart failure (NYHA class III or IV) Severe pulmonary disease (GOLD III or IV) HIV infection (AIDS criteria)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Multicenter open label randomized controlled clinical trial
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Plasma exchange<br>Plasma exchange with human serum albumin + Polyclonal immunoglobulin + standard medical treatment | Biological: Plasma exchange<br>* Plasma exchanges with 5% human albumin and fresh frozen plasma in patients with quick <50% or only with 5% albumin in patients with quick of 50% or more. We will exchange between 1.2 and 1.5 plasma volumes, that will vary according to sex, weight, height and hematocrit. Polyclonal immunoglobulin will be administered at a dose of 100 mg / kg ev after each plasma exchange. Standar Medical treatment Kaletra: lopinavir/ritonavir: 2c/12h 7 days Hydroxychloroquine sulfate 400 mg/12h the first day followed by 200 mg /12h 4 days Azithromycin 500 mg first day, followed by 250 mg /d 4 days (oral or EV) Tocilizumab 400 mg (weight <75Kgs) or 600 mg (weight ≥ 75 Kg) Methylprednisolone 250 mg EV three days and 30 mg/d another 3 days Anakinra 200mg/ 12h SBC first day, 200mg / 24h SBC two more days Clexane 40-60 mg/d<br>|
| Active Comparator: Standar medical treatment<br>Standar medical treatment | Drug: Standar medical treatmen<br>* Kaletra: lopinavir/ritonavir: 2c/12h 7 days Hydroxychloroquine sulfate 400 mg/12h the first day followed by 200 mg /12h 4 days Azithromycin 500 mg first day, followed by 250 mg /d 4 days (oral or EV) Tocilizumab 400 mg (weight <75Kgs) or 600 mg (weight ≥ 75 Kg) Methylprednisolone 250 mg EV three days and 30 mg/d another 3 days Anakinra 200mg/ 12h SBC first day, 200mg / 24h SBC two more days Clexane 40-60 mg/d<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Impact of plasma exchange | Number of exitus at 28 days after plasma exchange in patients with COVID-19 disease and invasive mechanical ventilation. | 28 days |