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

NCT04366089 | Unknown Phase 2 DMC

• 1 other identifier: 110/2020
• Study Type: interventional
• Target: 152
• Locations: 1 country
• Sites: 1

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.

Conditions

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

Keywords

Oxygen-ozone therapy; gut microbiota

Outcome Measures

Primary Outcomes (1)

• Delta in the number of patients requiring orotracheal intubation despite treatment

  Comparison between the two groups

  21 days

Secondary Outcomes (12)

• Delta of crude mortality

  21 days

• Delta of length of stay for patients in hospital

  90 days

• delta in the value of interleukin (IL)-1

  21 days

• delta in the value of IL-6

  21 days

• delta in the value of IL-10

  21 days

Study Arms (2)

Standard of care

ACTIVE COMPARATOR

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.

Drug: Azithromycin; Drug: hydroxychloroquine

Oxygen-ozone and probiotic

EXPERIMENTAL

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).

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

Interventions

Oxygen-ozone therapy, probiotic supplementation and Standard of care OTHER

\- systemic autohemotherapy with Ozone 30 mcg / ml 250ml 2 times / day for 7 days

Oxygen-ozone and probiotic

SivoMixx (200 billion) DIETARY_SUPPLEMENT

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)

Oxygen-ozone and probiotic

Azithromycin DRUG

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)

Oxygen-ozone and probiotic; Standard of care

hydroxychloroquine DRUG

dose: 200 mg, 1 cp x 2 / day

Oxygen-ozone and probiotic; Standard of care

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Roberto Poscia MD, PhD: lead

Study Sites (1)

Francesco Pugliese

Rome, RM, 00161, Italy

RECRUITING

Related Publications (3)

• 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.

  PMID: 32303365 RESULT

• 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.

  PMID: 32228825 RESULT

• 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/

  PMID: 32150360 RESULT

Related Links

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

MeSH Terms

Conditions

Pneumonia, Viral; Coronavirus Infections

Interventions

Standard of Care; Azithromycin; Hydroxychloroquine

Condition Hierarchy (Ancestors)

Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Lung Diseases; Respiratory Tract Diseases; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections

Intervention Hierarchy (Ancestors)

Quality Indicators, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation; Erythromycin; Macrolides; Polyketides; Lactones; Organic Chemicals; Chloroquine; Aminoquinolines; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Francesco Pugliese, MD, PhD

  University of Rome Sapienza - Policlinico Umberto I Rome (Italy)

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Francesco Pugliese, MD, PhD

CONTACT

00390649978024; f.pugliese@uniroma1.it

Fabio Araimo, MD

CONTACT

f.araimo@policlinicoumberto1.it

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Medical Doctor

Study Record Dates

• First Submitted: April 22, 2020
• First Posted: April 28, 2020
• Study Start: March 26, 2020
• Primary Completion: October 30, 2020
• Study Completion: December 31, 2020
• Last Updated: April 28, 2020

Record last verified: 2020-04

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)