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

COVID Clinical Trial

— PROBIOZOVID  

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04366089
• Other study ID #: 110/2020
• Status: Recruiting
• Phase: Phase 2
• Start date: March 26, 2020
• Est. completion date: December 31, 2020

Study information

• Verified date: April 2020
• Source: Azienda Policlinico Umberto I
• Contact: Francesco Pugliese, MD, PhD
• Phone: 00390649978024
• Email: f.pugliese[@]uniroma1.it
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 152
• Est. completion date: December 31, 2020
• Est. primary completion date: October 30, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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)"

Related Conditions & MeSH terms

• Coronavirus Infection
• Coronavirus Infections
• COVID
• Pneumonia
• Pneumonia, Viral
• SARS-CoV 2
• Severe Acute Respiratory Syndrome

Intervention

Other:
• Oxygen-ozone therapy, probiotic supplementation and Standard of care
- systemic autohemotherapy with Ozone 30 mcg / ml 250ml 2 times / day for 7 days

Dietary Supplement:
• SivoMixx (200 billion)
Composition of SivoMixx: Streptococcus thermophilus DSM322245, Bifidobacterium lactis DSM 32246, Bifidobacterium lactis DSM 32247, Lactobacillus acidophilus DSM 32241, Lactobacillus helveticus DSM 32242, Lactobacillus paracasei DSM 32243, Lactobacillus plantarum DSM 32244, Lactobacillus brevis DSM 27961 (NB: DSM n°... : bacterial strain identification code)

Drug:
• Azithromycin
dose: 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)
• hydroxychloroquine
dose: 200 mg, 1 cp x 2 / day

Locations

Country	Name	City	State
Italy	Francesco Pugliese	Rome	RM

Sponsors (1)

Lead Sponsor	Collaborator
Roberto Poscia MD, PhD

Country where clinical trial is conducted

Italy, 

References & Publications (4)

Cascella M, Rajnik M, Cuomo A, Dulebohn SC, Di Napoli R. Features, Evaluation and Treatment Coronavirus (COVID-19). 2020 Mar 20. StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2020 Jan-. Available from http://www.ncbi.nlm.nih.gov/book — View Citation

Conti P, Gallenga CE, Tetè 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 Mar 31;34 — View Citation

Hernández A, Papadakos PJ, Torres A, González 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. 2020 Apr 14. pii: S0034-9356(20)30075-X. doi: 10. — View Citation

Xu K, Cai H, Shen Y, Ni Q, Chen Y, Hu S, Li J, Wang H, Yu L, Huang H, Qiu Y, Wei G, Fang Q, Zhou J, Sheng J, Liang T, Li L. [Management of corona virus disease-19 (COVID-19): the Zhejiang experience]. Zhejiang Da Xue Xue Bao Yi Xue Ban. 2020 Feb 21;49(1): — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Delta in the number of patients requiring orotracheal intubation despite treatment	Comparison between the two groups	21 days
Secondary	Delta of crude mortality	Comparison between the two groups	21 days
Secondary	Delta of length of stay for patients in hospital	Comparison between the two groups	90 days
Secondary	delta in the value of interleukin (IL)-1	Comparison between the two groups	21 days
Secondary	delta in the value of IL-6	Comparison between the two groups	21 days
Secondary	delta in the value of IL-10	Comparison between the two groups	21 days
Secondary	delta in the value of Tumor Necrosis Factor (TNF)-alpha	Comparison between the two groups	21 days
Secondary	delta in the value of cluster of differentiation (CD)4+ CD38/ Human Leukocyte Antigen-DR isotype (HLA-DR)	Comparison between the two groups	21 days
Secondary	delta in the value of CD8+ CD38/ HLA-DR	Comparison between the two groups	21 days
Secondary	delta in the value of fecal calprotectin	Comparison between the two groups	21 days
Secondary	delta in the value of lipopolysaccharide (LPS)	Comparison between the two groups	21 days
Secondary	delta in the value of zonulin	Comparison between the two groups	21 days
Secondary	delta in the value of alpha1-antitrypsin	Comparison between the two groups	21 days

External Links

•   A multicenter randomized controlled trial for ozone autohemotherapy in the treatment of novel coronavirus pneumonia (COVID-19)
•   A randomized controlled trial for the efficacy of ozonated autohemotherapy in the treatment of Novel Coronavirus Pneumonia (COVID-19)
•   Clinical study for ozonated autohemotherapy in the treatment of Novel Coronavirus Pneumonia (COVID-19)