Oxygen-Ozone as Adjuvant Treatment in Early Control of COVID-19 Progression and Modulation of the Gut Microbial Flora (PROBIOZOVID)

Roberto Poscia MD, PhD

Status and phase: Unknown; Phase 2

Conditions: SARS-CoV 2; COVID; Pneumonia, Viral; Coronavirus Infection

Treatments: Other: Oxygen-ozone therapy, probiotic supplementation and Standard of care; Dietary Supplement: SivoMixx (200 billion); Drug: Azithromycin; Drug: hydroxychloroquine

Study type: Interventional

Funder types: Other

Identifiers

NCT04366089

110/2020

Details and patient eligibility

About

Italy was the first European country affected by a severe outbreak of the Severe Acute Respiratory Syndrome - CoronaVirus-2 (SARS-CoV-2) epidemic emerged from Wuhan region (China), with a high morbidity and mortality associated with the disease.

In light of its pandemic spread and the very limited therapeutic options, COronaVIrus Disease 19 (COVID-19) is considered an unprecedented global health challenge. Therefore, the evaluation of new resources, designed in the first instance for other pathologies but potentially active against COVID-19, represents a priority in clinical research.

This is an interventional, non-pharmacological, open, randomized, prospective, non-profit study on the adjuvant use of oxygen ozone therapy plus probiotic supplementation in the early control of disease progression in patients with COVID-19.

Contextually, all patients are treated with the current standard of care on the basis of the interim guidelines of the Italian Society of Infectious and Tropical Diseases.

The main purpose of the study is to evaluate the effectiveness of an ozone therapy-based intervention (accompanied by supplementation with probiotics) in containing the progression of COVID-19 and in preventing the need for hospitalization in intensive care units.

Full description

Several studies analyzed the mechanisms by which ozone therapy could combat viral infections. In particular, 1) the improvement of the release of oxygen in the peripheral tissues, 2) the anti-inflammatory action 3) a virucidal activity have been described.

In view of these properties, a number of international clinical trials on the topic are currently ongoing.

Hospitalization, dietary changes, use of antibiotics and systemic inflammation related to COVID-19 are all variables that contribute to changes in the intestinal and lung microbiota with significant repercussions on the outcomes of the disease. Furthermore, the use of ozone therapy could also lead to a modification of the microbial flora. Probiotic supplementation can help to correct these issues.

Enrollment: 152 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Age > 18 years
• Nasopharyngeal swab positive for COVID-19
• COVID-19 stages I - II - III (*1)
• Hospitalization in the Department of Infectious Diseases

Exclusion criteria

• COVID-19 stages IV - V - VI (*1)
• Hospitalization in Intensive Care Units
• Pregnancy
• Glucose-6-phosphate dehydrogenase (G6PD) deficiency
• Patients who deny consent to the proposed treatment
• Inability to provide informed consent
• Contraindications to performing oxygen-ozone therapy
• hyperhomocysteinemia
• favism or thyroiditis
• coagulopathies
• neurodegenerative diseases
• angina (in particular Prinzmetal's angina) or with previous myocardial infarction

(*1) Compliant with indications published by:

Italian Society of Anesthesia Analgesia Resuscitation and Intensive Care (SIAARTI).

Care pathway for the patient with COVID-19.

Section 2 - Recommendations for local management of the critically ill patient - Version 2

Available on http://www.siaarti.it/SiteAssets/News/COVID19%20-%20documenti%20SIAARTI/Percorso%20COVID-19%20-%20Sezione%202%20-%20Raccomandazioni%20per%20la%20gestione%20locale%20-%20Rev%202.0.pdf

Last accessed 20/04/2020

Posted on 26.03.2020

On page 2 of the previous document :

"6 identified stages:

• sick disease - mild COVID-19 (I stage)
• light pneumonia - mild COVID-19 (II stage)
• serious pneumonia - severe COVID-19 (III stage)
• Acute respiratory distress syndrome (ARDS) - critical COVID-19 (IV stage)
• sepsis - critical COVID-19 (V stage)
• septic shock - critical COVID-19 (VI stage)"

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

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152 participants in 2 patient groups

Standard of care

Active Comparator group

Description:

Azithromycin 500mg 1 cp / day (alternatively lopinavir/ritonavir cps 200/50 mg, 2 cps x 2 / day or darunavir 800 mg 1 cp / day + ritonavir 100 mg 1 cp / day or darunavir/cobicistat 800/150 mg 1 cp / day), plus hydroxychloroquine cp 200 mg, 1 cp x 2 / day.

Treatment:

Drug: hydroxychloroquine

Drug: Azithromycin

Oxygen-ozone and probiotic

Experimental group

Description:

Oxygen-ozone therapy, probiotic supplementation plus standard of care Oxygen-ozone therapy: systemic autohemotherapy (twice a day). Probiotic supplementation: SivoMixx 200 billion (six sachets twice a day).

Treatment:

Drug: hydroxychloroquine

Other: Oxygen-ozone therapy, probiotic supplementation and Standard of care

Drug: Azithromycin

Dietary Supplement: SivoMixx (200 billion)