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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04366089
Recruitment Status : Unknown
Verified April 2020 by Roberto Poscia MD, PhD, Azienda Policlinico Umberto I.
Recruitment status was:  Recruiting
First Posted : April 28, 2020
Last Update Posted : April 28, 2020
Sponsor:
Information provided by (Responsible Party):
Roberto Poscia MD, PhD, Azienda Policlinico Umberto I

Study Description
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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.


Condition or disease Intervention/treatment Phase
COVID SARS-CoV 2 Pneumonia, Viral Coronavirus Infection Other: Oxygen-ozone therapy, probiotic supplementation and Standard of care Dietary Supplement: SivoMixx (200 billion) Drug: Azithromycin Drug: hydroxychloroquine Phase 2

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.

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 152 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary Purpose: Treatment
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
Actual Study Start Date : March 26, 2020
Estimated Primary Completion Date : October 30, 2020
Estimated Study Completion Date : December 31, 2020

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Active Comparator: Standard of care
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
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)

Drug: hydroxychloroquine
dose: 200 mg, 1 cp x 2 / day
Experimental: Oxygen-ozone and probiotic

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
- 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)

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


Outcome Measures
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Primary Outcome Measures :
  1. Delta in the number of patients requiring orotracheal intubation despite treatment [ Time Frame: 21 days ]
    Comparison between the two groups


Secondary Outcome Measures :
  1. Delta of crude mortality [ Time Frame: 21 days ]
    Comparison between the two groups

  2. Delta of length of stay for patients in hospital [ Time Frame: 90 days ]
    Comparison between the two groups

  3. delta in the value of interleukin (IL)-1 [ Time Frame: 21 days ]
    Comparison between the two groups

  4. delta in the value of IL-6 [ Time Frame: 21 days ]
    Comparison between the two groups

  5. delta in the value of IL-10 [ Time Frame: 21 days ]
    Comparison between the two groups

  6. delta in the value of Tumor Necrosis Factor (TNF)-alpha [ Time Frame: 21 days ]
    Comparison between the two groups

  7. delta in the value of cluster of differentiation (CD)4+ CD38/ Human Leukocyte Antigen-DR isotype (HLA-DR) [ Time Frame: 21 days ]
    Comparison between the two groups

  8. delta in the value of CD8+ CD38/ HLA-DR [ Time Frame: 21 days ]
    Comparison between the two groups

  9. delta in the value of fecal calprotectin [ Time Frame: 21 days ]
    Comparison between the two groups

  10. delta in the value of lipopolysaccharide (LPS) [ Time Frame: 21 days ]
    Comparison between the two groups

  11. delta in the value of zonulin [ Time Frame: 21 days ]
    Comparison between the two groups

  12. delta in the value of alpha1-antitrypsin [ Time Frame: 21 days ]
    Comparison between the two groups


Eligibility Criteria
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Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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)"
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04366089


Contacts
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Contact: Francesco Pugliese, MD, PhD 00390649978024 f.pugliese@uniroma1.it
Contact: Fabio Araimo, MD f.araimo@policlinicoumberto1.it

Locations
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Italy
Francesco Pugliese Recruiting
Rome, RM, Italy, 00161
Contact: Francesco Pugliese, MD PhD    00390649978024    f.pugliese@uniroma1.it   
Sub-Investigator: Fabio Araimo, MD         
Sub-Investigator: Carmela Imperiale, MD         
Sub-Investigator: Paolo Tordiglione, MD PhD         
Sub-Investigator: Claudio M Mastroianni, MD PhD         
Sub-Investigator: Gabriella d'Ettorre, MD PhD         
Sub-Investigator: Giancarlo Ceccarelli, MD PhD MSc         
Sub-Investigator: Andrea Calò, MD         
Sub-Investigator: Vera MAuro, MD         
Sub-Investigator: Serena Zancla, MD         
Sub-Investigator: Gregorio Egidio Recchia, MD         
Sponsors and Collaborators
Roberto Poscia MD, PhD
Investigators
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Principal Investigator: Francesco Pugliese, MD, PhD University of Rome Sapienza - Policlinico Umberto I Rome (Italy)
More Information
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Additional Information:

Publications of Results:

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Responsible Party: Roberto Poscia MD, PhD, Medical Doctor, Azienda Policlinico Umberto I
ClinicalTrials.gov Identifier: NCT04366089    
Other Study ID Numbers: 110/2020
First Posted: April 28, 2020    Key Record Dates
Last Update Posted: April 28, 2020
Last Verified: April 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Roberto Poscia MD, PhD, Azienda Policlinico Umberto I:
Oxygen-ozone therapy
gut microbiota
Additional relevant MeSH terms:
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Coronavirus Infections
Pneumonia, Viral
Pneumonia
Respiratory Tract Infections
Infections
Lung Diseases
Respiratory Tract Diseases
Coronaviridae Infections
Nidovirales Infections
RNA Virus Infections
Virus Diseases
 Azithromycin
Hydroxychloroquine
Anti-Bacterial Agents
Anti-Infective Agents
Antimalarials
Antiprotozoal Agents
Antiparasitic Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antirheumatic Agents