Ozone Auto-hemotherapy for COVID-19 Pneumonia (COVID-OZONE)

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

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

Study Overview

• Status: Unknown
• Conditions: COVID-19 Pneumonia
• Intervention / Treatment: Biological: Ozone auto-hemotherapy

• Study Type: Interventional
• Enrollment (Anticipated): 208
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Alberto Hernández, MD, PhD; Phone Number: +34 637930993; Email: albimar23@yahoo.es
• Study Contact Backup: Name: Marc Vives, MD, PhD; Phone Number: +34 690277088; Email: marcvives50@gmail.com

Study Locations

• Spain
  • Girona, Spain, 17007
    • Hospital Universitari Dr Josep Trueta
  • Ibiza, Spain
    • Clinica Nuestra Señora del Rosario
  • Madrid, Spain
    • Hospital Universitario 12 de Octubre
    • Contact: Noelia Zurera Plaza, MD
  • Madrid, Spain
    • Hospital Universitario Infanta Leonor
    • Contact: Javier Ripolles, MD, PhD
  • Madrid, Spain
    • Hospital Quirón Rey Juan Carlos I
  • Madrid, Spain
    • Hospital Universitario Príncipe de Asturias de Alcalá de Henares
    • Contact: Miguel Angel Garcia, MD
  • Manresa, Spain
    • Fundació Althaia de Manresa
    • Contact: Antònia Flor, MD
  • Valencia, Spain
    • Hospital Vithas Valencia Consuelo
    • Contact: Jose Baeza, MD
  • Valladolid, Spain
    • Hospital Clínico Universitario de Valladolid
    • Contact: Eduardo Tamayo, MD, PhD
  • Vigo, Spain
    • Clinica Claro

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 90 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Ozone auto-hemotherapy plus standard treatment; 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; ozone auto-hemotherapy
No Intervention: Standard treatment alone; 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

Collaborators and Investigators

• Sponsor: Institut d'Investigació Biomèdica de Girona Dr. Josep Trueta
• Collaborators: Clinica Nuestra Senora del Rosario

Study record dates

Study Major Dates

• Study Start (Anticipated): May 25, 2020
• Primary Completion (Anticipated): October 25, 2020
• Study Completion (Anticipated): December 25, 2020

Study Registration Dates

• First Submitted: April 27, 2020
• First Submitted That Met QC Criteria: April 29, 2020
• First Posted (Actual): April 30, 2020

Study Record Updates

• Last Update Posted (Actual): June 9, 2020
• Last Update Submitted That Met QC Criteria: June 4, 2020
• Last Verified: June 1, 2020

More Information

Terms related to this study

• Keywords: Covid-19; SARS-COV-2; Ozone therapy
• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Lung Diseases; COVID-19; Pneumonia
• Other Study ID Numbers: COVID-19 Networking group

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No