Ozone Auto-hemotherapy for COVID-19 Pneumonia

Study Overview
=================
Brief Summary
-----------------
This is a multicenter, randomized, controlled, open-label clinical trial testing the use of ozone auto-hemotherapy in hospitalized patients with Covid-19 pneumonia. Eligible patients will be randomly assigned to receive either ozone auto-hemotherapy plus standard treatment, or standard treatment alone. Patients in the ozone auto-hemotherapy group will receive treatment mixing 100-200ml of blood with ozone at a concentration of 40 μg / mL with a gas volume of 200 ml. Treatment will occur every 12h during 5 days. Standard treatment will be the one used in each hospital participating in the trial. All analyses will be done according to the intention-to-treat principle

Official Title
-----------------
A Trial of Ozone Auto-hemotherapy in Adults Hospitalized With Covid-19 Pneumonia

Conditions
-----------------
COVID-19 Pneumonia

Intervention / Treatment
-----------------
* Biological: Ozone auto-hemotherapy


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Diagnosis of COVID-19 confirmed by positive polymerase chain reaction (PCR) for Severe Acute Respiratory Syndrome (SARS-COV-2) in respiratory tract sample, plus pneumonia confirmed by imaging tests and arterial oxygen saturation (SpO2) <94% with ambient air or a partial pressure of oxygen to fraction of inspired oxygen (pO2/FiO2) ratio <300 mmHg or SpO2/FiO2 ≤ 315. Acceptance to participate in the study and signing of the informed consent. Exclusion Criteria: Patients who have received treatment with any form of ozone therapy 6 months before admission to the hospital. Patients who have previously been treated and have experienced some type of adverse reaction to ozone therapy. Patients aware of having a deficiency of Glucose-6-phosphate dehydrogenase. Patients with clinically decompensated chronic comorbidities, independently of COVID-19. Patients suffering from any psychiatric disorder specified in axis I of the Diagnostic and Statistical Manual of Mental Disorders (DSM-V), other than major depression. Patients who are not able to clearly understand the objectives and methodology of the study. Pregnant or lactating patients.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 90 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
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ozone auto-hemotherapy plus standard treatment<br>Patients in the ozone auto-hemotherapy group will receive treatment mixing 100-200ml of blood with ozone at a concentration of 40 μg / mL with a gas volume of 200 ml. Treatment will occur every 12h during 5 days. | Biological: Ozone auto-hemotherapy<br>* ozone auto-hemotherapy<br>|
| No Intervention: Standard treatment alone<br>Standard treatment will be the one used in each hospital participating in the trial. | |

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of patients achieving improvement in clinical condition at day 14 after recruitment | Improved clinical condition defined by an improvement of 2 points in the clinical status, 8 categories, ordinary score of the World Health Organization (WHO) | 14 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mortality at day 28 | mortality | 28 days | 
| Rate of patients achieving improvement in clinical condition at day 28 after recruitment | Improved clinical condition defined by an improvement of 2 points in the clinical status, 8 categories, ordinary score of the World Health Organization (WHO) | 28 days | 
| Rate of patients achieving improvement in clinical condition at day 7 after recruitment | Improved clinical condition defined by an improvement of 2 points in the clinical status, 8 categories, ordinary score of the World Health Organization (WHO) | 7 days | 
| Time to clinical improvement or hospital discharge | Improved clinical condition defined by an improvement of 2 points in the clinical status, 8 categories, ordinary score of the World Health Organization (WHO) | 28 days | 
| Number of ventilator-free days at 28 days | Ventilator-free days from last extubation day until day 28 after recruitment | 28 days | 
| Hospital length of stay | Days hospitalized | 28 days | 
| Time to a 2-fold decrease in ferritin | Number of days until a 2-fold decrease in ferritin (ng/mL) | 14 days | 
| Time to a 2-fold decrease in C-protein reactive | Number of days until a 2-fold decrease in C-Protein Reactive (mg/L) | 14 days | 
| Time to a 2-fold decrease in Dimer-D | Number of days until a 2-fold decrease in Dimer-D (ng/mL) | 14 days | 
| Time to a 2-fold decrease in Lactate Dehydrogenase | Number of days until a 2-fold decrease in Lactate Dehydrogenase (U/L) | 14 days | 
| Time to a 2-fold decrease in Neutrophils to Lymphocytes ratio | Number of days until a 2-fold decrease in Neutrophils to Lymphocytes ratio | 14 days | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Ozone therapy, Covid-19, SARS-COV-2