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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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04366089
Recruitment Status : 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

Tracking Information
First Submitted Date  ICMJE April 22, 2020
First Posted Date  ICMJE April 28, 2020
Last Update Posted Date April 28, 2020
Actual Study Start Date  ICMJE March 26, 2020
Estimated Primary Completion Date October 30, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 27, 2020)
Delta in the number of patients requiring orotracheal intubation despite treatment [ Time Frame: 21 days ]
Comparison between the two groups
Original Primary Outcome Measures  ICMJE Same as current
Change History No Changes Posted
Current Secondary Outcome Measures  ICMJE
 (submitted: April 27, 2020)
  • Delta of crude mortality [ Time Frame: 21 days ]
    Comparison between the two groups
  • Delta of length of stay for patients in hospital [ Time Frame: 90 days ]
    Comparison between the two groups
  • delta in the value of interleukin (IL)-1 [ Time Frame: 21 days ]
    Comparison between the two groups
  • delta in the value of IL-6 [ Time Frame: 21 days ]
    Comparison between the two groups
  • delta in the value of IL-10 [ Time Frame: 21 days ]
    Comparison between the two groups
  • delta in the value of Tumor Necrosis Factor (TNF)-alpha [ Time Frame: 21 days ]
    Comparison between the two groups
  • 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
  • delta in the value of CD8+ CD38/ HLA-DR [ Time Frame: 21 days ]
    Comparison between the two groups
  • delta in the value of fecal calprotectin [ Time Frame: 21 days ]
    Comparison between the two groups
  • delta in the value of lipopolysaccharide (LPS) [ Time Frame: 21 days ]
    Comparison between the two groups
  • delta in the value of zonulin [ Time Frame: 21 days ]
    Comparison between the two groups
  • delta in the value of alpha1-antitrypsin [ Time Frame: 21 days ]
    Comparison between the two groups
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Oxygen-Ozone as Adjuvant Treatment in Early Control of COVID-19 Progression and Modulation of the Gut Microbial Flora
Official Title  ICMJE Oxygen-Ozone as Adjuvant Treatment in Early Control of Disease Progression in Patients With COVID-19 Associated With Modulation of the Gut Microbial Flora
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE
  • COVID
  • SARS-CoV 2
  • Pneumonia, Viral
  • Coronavirus Infection
Intervention  ICMJE
  • 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
Study Arms  ICMJE
  • 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.
    Interventions:
    • Drug: Azithromycin
    • Drug: hydroxychloroquine
  • 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).

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

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: April 27, 2020)
152
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 31, 2020
Estimated Primary Completion Date October 30, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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)"
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Francesco Pugliese, MD, PhD 00390649978024 f.pugliese@uniroma1.it
Contact: Fabio Araimo, MD f.araimo@policlinicoumberto1.it
Listed Location Countries  ICMJE Italy
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04366089
Other Study ID Numbers  ICMJE 110/2020
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Roberto Poscia MD, PhD, Azienda Policlinico Umberto I
Study Sponsor  ICMJE Roberto Poscia MD, PhD
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Francesco Pugliese, MD, PhD University of Rome Sapienza - Policlinico Umberto I Rome (Italy)
PRS Account Azienda Policlinico Umberto I
Verification Date April 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP