Pilot Study on Cytokine Filtration in COVID-19 ARDS

Study Overview
=================
Brief Summary
-----------------
Background: There are no proven therapies for COVID-19 infection. COVID-19 infects the respiratory epithelium of the lower airways, causing widespread damage via cytopathic effects, resulting in severe inflammation and Pneumonitis. High local and circulating levels of cytokines, or cytokine storm, can lead to capillary leak syndrome, progressive lung injury, respiratory failure and acute respiratory distress syndrome (ARDS). Methods: This is a pilot randomized, controlled, uni-center study testing safety and efficacy of cytokine filtration on patients with severe ARDS. Eligible patients will be randomized to 72 hours filtration or no filtration on top of the standard treatment for ARDS. Indications for randomization are patients with moderate or severe ARDS with need of ventilation support (either invasive or non-invasive), with inflammatory markers. The primary outcome will be days on mechanical ventilation (MV) support. Secondary outcomes are 30-day mortality, ICU days, need for extracorporeal membrane oxygenation (ECMO) support, duration of renal replacement therapy (RRT) and catecholamine therapies, hospital length of stay, multi-organ failure. All analysis will be done according to the intention to treat principle.

Official Title
-----------------
Pilot Study on Cytokine Filtration in COVID-19 ARDS (CytokCOVID19)

Conditions
-----------------
Coronavirus Infection, Acute Respiratory Distress Syndrome, COVID

Intervention / Treatment
-----------------
* Device: Cytokine Adsorption


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Age 18 or older Positive revere transcription polymerase chain reaction (RT-PCR) for COVID-19 in a respiratory track sample Acute (less than 36 hours) onset of moderate to severe ARDS, as defined by Berlin criteria: Having pneumonia or worsening respiratory symptoms Bilateral pulmonary infiltrates on chest imaging (X-ray of CT scan) Pulmonary wedge pressure <18 mmHg or no clinical signs of left heart failure Hypoxemia: arterial oxygen pressure/Fraction of inspired oxygen (PaO2/FiO2 ratio) <200mmHg, moderate dyspnea with signs of important respiratory workload, tachypnoea >30bpm Rise of inflammatory biomarkers: C-reactive protein (CRP) >10 mg/L Exclusion Criteria: Patients with a known contraindication for anticoagulation Pregnancy or breast feeding Patient already included in another research study Decision by a physician that involvement in the study is not in the patient's best interest Failure to have patient's authorization. In case of a mechanical intubated patient, lack of authorization from a first line family member Multi-organ failure Patients treated with Tocilizumab at the time of start filtration

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: This is a two-branch randomized, controlled, uni-center study. Eligible patients will be randomly assigned in a 1:1 ratio to receive cytokine filtration plus standard intensive care, or standard intensive care alone
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Control<br>standard intensive care alone | |
| Experimental: Cytokine Adsorption<br>cytokine adsorption plus standard intensive care | Device: Cytokine Adsorption<br>* Cytokine adsorption will be performed through a venous hemodialysis catheter, preferably jugular or femoral. The filtration system will be established with a cytokine adsorption cartridge in an hemoperfusion system using a blood flow rate of 150 - 200 ml/min. Adsorbent therapy will last 72 hours, changing cartridges every 24 hours. Prior to start, heparinization will be stablished by a 1mg/Kg iv Na heparin bolus plus iv perfusion. Activated Partial Thromboplastin Time (aPTT) control will be performed every 6 hours, with a goal range between 60 and 80 seconds.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mechanical ventilation-free days | Number of ventilator-free days (VFDs) at day 28 (defined as days being alive and free from mechanical ventilation at day 28 after enrollment. For patients ventilated 28 days or longer and for ventilated subjects who die, VFD is 0 | up to 28days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 30-day mortality |  | up to 30 days | 
| length of ICU stay (days) |  | up to 30 days | 
| length of hospital stay |  | up to 30 days | 
| Duration of renal replacement and cathecolamines therapies |  | up to 30 days | 
| Need for extracorporeal membrane oxygenation (ECMO) support |  | up to 30 days | 
| multi-organ failure measured by the Sequential Organ Failure Assessment (SOFA) score |  | up to 30 days (measured on days 0, 1, 2, 3, 4, 5, 6, and the last day of mechanical ventilation) | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
COVID, ARDS, Coronavirus