Clinical trial NCT04366089: Oxygen-Ozone as Adjuvant Treatment in Early Control of COVID-19 Progression and Modulation of the Gut Microbial Flora
Official title: Oxygen-Ozone as Adjuvant Treatment in Early Control of Disease Progression in Patients With COVID-19 Associated With Modulation of the Gut Microbial Flora
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: COVID
SARS-CoV 2
Pneumonia, Viral
Coronavirus Infection
Keywords: Oxygen-ozone therapy
gut microbiota
Lead sponsor: Azienda Policlinico Umberto I
Sponsor class: OTHER
First posted: 2020-04-28
Enrollment: 152
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

Detailed 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.

Eligibility criteria: 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)"

Primary outcomes:
measure: Delta in the number of patients requiring orotracheal intubation despite treatment
timeFrame: 21 days
Secondary outcomes:
measure: Delta of crude mortality
timeFrame: 21 days
measure: Delta of length of stay for patients in hospital
timeFrame: 90 days
measure: delta in the value of interleukin (IL)-1
timeFrame: 21 days
measure: delta in the value of IL-6
timeFrame: 21 days
measure: delta in the value of IL-10
timeFrame: 21 days
measure: delta in the value of Tumor Necrosis Factor (TNF)-alpha
timeFrame: 21 days
measure: delta in the value of cluster of differentiation (CD)4+ CD38/ Human Leukocyte Antigen-DR isotype (HLA-DR)
timeFrame: 21 days
measure: delta in the value of CD8+ CD38/ HLA-DR
timeFrame: 21 days
measure: delta in the value of fecal calprotectin
timeFrame: 21 days
measure: delta in the value of lipopolysaccharide (LPS)
timeFrame: 21 days
measure: delta in the value of zonulin
timeFrame: 21 days
measure: delta in the value of alpha1-antitrypsin
timeFrame: 21 days
Other outcomes:
Locations:
city: Rome
country: Italy
facility: Francesco Pugliese
state: RM
Study officials:
affiliation: University of Rome Sapienza - Policlinico Umberto I Rome (Italy)
name: Francesco Pugliese, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Hernandez A, Papadakos PJ, Torres A, Gonzalez DA, Vives M, Ferrando C, Baeza J. Two known therapies could be useful as adjuvant therapy in critical patients infected by COVID-19. Rev Esp Anestesiol Reanim (Engl Ed). 2020 May;67(5):245-252. doi: 10.1016/j.redar.2020.03.004. Epub 2020 Apr 14.
citation: Conti P, Gallenga CE, Tete G, Caraffa A, Ronconi G, Younes A, Toniato E, Ross R, Kritas SK. How to reduce the likelihood of coronavirus-19 (CoV-19 or SARS-CoV-2) infection and lung inflammation mediated by IL-1. J Biol Regul Homeost Agents. 2020 March-April,;34(2):333-338. doi: 10.23812/Editorial-Conti-2.
citation: Cascella M, Rajnik M, Aleem A, Dulebohn SC, Di Napoli R. Features, Evaluation, and Treatment of Coronavirus (COVID-19). 2023 Aug 18. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan-. Available from http://www.ncbi.nlm.nih.gov/books/NBK554776/