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

Primary Purpose

COVID, SARS-CoV 2, Pneumonia, Viral

Status
Unknown status
Phase
Phase 2
Locations
Italy
Study Type
Interventional
Intervention
Oxygen-ozone therapy, probiotic supplementation and Standard of care
SivoMixx (200 billion)
Azithromycin
hydroxychloroquine
Sponsored by
Roberto Poscia MD, PhD
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for COVID focused on measuring Oxygen-ozone therapy, gut microbiota

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept 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)"

Sites / Locations

  • Francesco PuglieseRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Experimental

Arm Label

Standard of care

Oxygen-ozone and probiotic

Arm 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.

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).

Outcomes

Primary Outcome Measures

Delta in the number of patients requiring orotracheal intubation despite treatment
Comparison between the two groups

Secondary Outcome Measures

Delta of crude mortality
Comparison between the two groups
Delta of length of stay for patients in hospital
Comparison between the two groups
delta in the value of interleukin (IL)-1
Comparison between the two groups
delta in the value of IL-6
Comparison between the two groups
delta in the value of IL-10
Comparison between the two groups
delta in the value of Tumor Necrosis Factor (TNF)-alpha
Comparison between the two groups
delta in the value of cluster of differentiation (CD)4+ CD38/ Human Leukocyte Antigen-DR isotype (HLA-DR)
Comparison between the two groups
delta in the value of CD8+ CD38/ HLA-DR
Comparison between the two groups
delta in the value of fecal calprotectin
Comparison between the two groups
delta in the value of lipopolysaccharide (LPS)
Comparison between the two groups
delta in the value of zonulin
Comparison between the two groups
delta in the value of alpha1-antitrypsin
Comparison between the two groups

Full Information

First Posted
April 22, 2020
Last Updated
April 27, 2020
Sponsor
Roberto Poscia MD, PhD
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1. Study Identification

Unique Protocol Identification Number
NCT04366089
Brief Title
Oxygen-Ozone as Adjuvant Treatment in Early Control of COVID-19 Progression and Modulation of the Gut Microbial Flora
Acronym
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
Study Type
Interventional

2. Study Status

Record Verification Date
April 2020
Overall Recruitment Status
Unknown status
Study Start Date
March 26, 2020 (Actual)
Primary Completion Date
October 30, 2020 (Anticipated)
Study Completion Date
December 31, 2020 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Roberto Poscia MD, PhD

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
COVID, SARS-CoV 2, Pneumonia, Viral, Coronavirus Infection
Keywords
Oxygen-ozone therapy, gut microbiota

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
Outcomes Assessor
Allocation
Randomized
Enrollment
152 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Standard of care
Arm Type
Active Comparator
Arm 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.
Arm Title
Oxygen-ozone and probiotic
Arm Type
Experimental
Arm 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).
Intervention Type
Other
Intervention Name(s)
Oxygen-ozone therapy, probiotic supplementation and Standard of care
Intervention Description
- systemic autohemotherapy with Ozone 30 mcg / ml 250ml 2 times / day for 7 days
Intervention Type
Dietary Supplement
Intervention Name(s)
SivoMixx (200 billion)
Intervention Description
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)
Intervention Type
Drug
Intervention Name(s)
Azithromycin
Intervention Description
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)
Intervention Type
Drug
Intervention Name(s)
hydroxychloroquine
Intervention Description
dose: 200 mg, 1 cp x 2 / day
Primary Outcome Measure Information:
Title
Delta in the number of patients requiring orotracheal intubation despite treatment
Description
Comparison between the two groups
Time Frame
21 days
Secondary Outcome Measure Information:
Title
Delta of crude mortality
Description
Comparison between the two groups
Time Frame
21 days
Title
Delta of length of stay for patients in hospital
Description
Comparison between the two groups
Time Frame
90 days
Title
delta in the value of interleukin (IL)-1
Description
Comparison between the two groups
Time Frame
21 days
Title
delta in the value of IL-6
Description
Comparison between the two groups
Time Frame
21 days
Title
delta in the value of IL-10
Description
Comparison between the two groups
Time Frame
21 days
Title
delta in the value of Tumor Necrosis Factor (TNF)-alpha
Description
Comparison between the two groups
Time Frame
21 days
Title
delta in the value of cluster of differentiation (CD)4+ CD38/ Human Leukocyte Antigen-DR isotype (HLA-DR)
Description
Comparison between the two groups
Time Frame
21 days
Title
delta in the value of CD8+ CD38/ HLA-DR
Description
Comparison between the two groups
Time Frame
21 days
Title
delta in the value of fecal calprotectin
Description
Comparison between the two groups
Time Frame
21 days
Title
delta in the value of lipopolysaccharide (LPS)
Description
Comparison between the two groups
Time Frame
21 days
Title
delta in the value of zonulin
Description
Comparison between the two groups
Time Frame
21 days
Title
delta in the value of alpha1-antitrypsin
Description
Comparison between the two groups
Time Frame
21 days

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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)"
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Francesco Pugliese, MD, PhD
Phone
00390649978024
Email
f.pugliese@uniroma1.it
First Name & Middle Initial & Last Name or Official Title & Degree
Fabio Araimo, MD
Email
f.araimo@policlinicoumberto1.it
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Francesco Pugliese, MD, PhD
Organizational Affiliation
University of Rome Sapienza - Policlinico Umberto I Rome (Italy)
Official's Role
Principal Investigator
Facility Information:
Facility Name
Francesco Pugliese
City
Rome
State/Province
RM
ZIP/Postal Code
00161
Country
Italy
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Francesco Pugliese, MD PhD
Phone
00390649978024
Email
f.pugliese@uniroma1.it
First Name & Middle Initial & Last Name & Degree
Fabio Araimo, MD
First Name & Middle Initial & Last Name & Degree
Carmela Imperiale, MD
First Name & Middle Initial & Last Name & Degree
Paolo Tordiglione, MD PhD
First Name & Middle Initial & Last Name & Degree
Claudio M Mastroianni, MD PhD
First Name & Middle Initial & Last Name & Degree
Gabriella d'Ettorre, MD PhD
First Name & Middle Initial & Last Name & Degree
Giancarlo Ceccarelli, MD PhD MSc
First Name & Middle Initial & Last Name & Degree
Andrea Calò, MD
First Name & Middle Initial & Last Name & Degree
Vera MAuro, MD
First Name & Middle Initial & Last Name & Degree
Serena Zancla, MD
First Name & Middle Initial & Last Name & Degree
Gregorio Egidio Recchia, MD

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
32303365
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. English, Spanish.
Results Reference
result
PubMed Identifier
32228825
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.
Results Reference
result
PubMed Identifier
32150360
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; 2023 Jan-. Available from http://www.ncbi.nlm.nih.gov/books/NBK554776/
Results Reference
result
Links:
URL
http://www.chictr.org.cn/showproj.aspx?proj=49947
Description
Clinical study for ozonated autohemotherapy in the treatment of Novel Coronavirus Pneumonia (COVID-19)
URL
http://www.chictr.org.cn/showproj.aspx?proj=49737
Description
A randomized controlled trial for the efficacy of ozonated autohemotherapy in the treatment of Novel Coronavirus Pneumonia (COVID-19)
URL
http://www.chictr.org.cn/showproj.aspx?proj=49747
Description
A multicenter randomized controlled trial for ozone autohemotherapy in the treatment of novel coronavirus pneumonia (COVID-19)

Learn more about this trial

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

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