Blood Ozonization in Patients With SARS-CoV-2 Respiratory Failure

NCT ID: NCT04388514

Last Updated: 2020-05-14

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

UNKNOWN

Clinical Phase

NA

Total Enrollment

90 participants

Study Classification

INTERVENTIONAL

Study Start Date

2020-04-08

Study Completion Date

2020-10-08

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

Aim. The emerging outbreak of coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to spread worldwide. Beside the prescription of some promising drugs as chloroquine, azithromycin, antivirals (lopinavir/ritonavir, darunavir/cobicistat) and immunomodulating agents (steroids, tocilizumab), in our patients with mild to moderate pneumonia due to SARS-CoV-2 we planned a randomize study to evaluate, respect the best available therapy (BAT), the use of autohemotherapy treatement with an oxygen/ozone (O3) gaseous mixture as adjuvant therapy.

Design. Multicentric, randomized study.

Participants. Clinical presentations are based upon clinical phenotypes identified by the Italian Society of Emergency and Urgency Medicine (SIMEU - Società Italiana di Medicina di Emergenza-Urgenza) and patients that meet criteria of phenotypes 2 to 4 were treat with best available therapy (BAT), and randomized to receive or not O3-autohemotherapy.

Main outcome measures. The end-point were the time of respiratory improvement and earlier weaning from oxygen support: these parameters were included in the SIMEU clinical phenotypes classification.

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

Recruitment Details.

The investigator enrolled, in the study, subjects with COVID-19 modest to moderate respiratory insufficiency (SIMEU clinical phenotypes 2-4) thus cared in an infectious disease ward.

To note that The Italian Society of Emergency and Urgency Medicine (SIMEU - Società Italiana di Medicina di Emergenza-Urgenza) suggest to classified the COVID-19 patients in 5 clinical phenotypes:

* Phenotype 1: subjects with fever and without respiratory failure (normal Arterial Blood Gas analysis - ABG -, six-minute walking test - 6mWT - and Chest XR). These patients usually can manage at home maintaining quarantine period.
* Phenotype 2: subjects with fever but with ABG and/or Chest XR indicative of modest respiratory insufficiency (PO2\> 60 mmHg in ambient air) and / or pulmonary consolidation area. These patients need to be hospitalized because they can get quickly worse.
* Phenotype 3: subjects with fever associate to moderate-severe respiratory insufficiency (at triage PO2\< 60 mmHg in ambient air) and /or bilateral pulmonary consolidation area at Chest XR. These patients need to be treated with high flow oxygen therapy.
* Phenotype 4: subjects with respiratory failure with suspected ARDS (Adult Respiratory Distress Syndrome) or complicated pneumonia. These patients require hospitalization in sub-intensive care unit.
* Phenotype 5: subject with ARDS at the beginning. These patients will require Intensive Care Unit (ICU) admission and non-invasive positive pressure ventilation (NIPPV) or mechanical ventilation.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

SARS-CoV-2 Respiratory Failure

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

The study includes 2 arms:

* Arm A: Blood ozonization plus BAT (n= 45 subjects)
* Arm B: Standard of Care only without Blood ozonization (n= 45 subjects)

To note that the Standard of Care are therapy with antiretroviral therapy (lopinavir/ritonavir 2 tablets every 12 hours or darunavir/cobicistat 1 tablet per day) and hidrossycloroquine 400 mg every 12 hours then first day, followed by 200 mg every 12 hours for other 4 days
Primary Study Purpose

TREATMENT

Blinding Strategy

SINGLE

Investigators
Randomization, 1:1 ratio

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

Blood ozonization

Blood ozonization plus BAT

Group Type EXPERIMENTAL

Medical Ozone procedure

Intervention Type PROCEDURE

The systemic ozone treatment procedure was decided by the physician on duty and started preliminarily at the patient's bed with the drawing of autologous blood and, after proper O2/O3 mixing, with its re-infusion. After junction of an adequate venous patient's way with a dedicated latex free plastic bag containing 35 ml of sodium citrate, a blood amount of 200 ml is taken. At the end, the withdrawal line was washed and the re-infusion one was filled with saline solution. The blood, without any patient disconnection, was then mixed with a gas mixture of a 200 cc composed by 96% of Oxygen and 4% of Ozone with a therapeutic O3 range of 40 μg/mL of gas per mL of blood. In order to guarantee the O2/O3 homogeneous diffusion into the blood, the bag was gently mixed for about 10 minutes, therefore the blood was re-infused into the patients. The duration of ozone treatment lasted for 3 consecutive days.

Standard of Care

BAT "only"

To note that the BAT are therapy with antiretroviral therapy (lopinavir/ritonavir 2 tablets every 12 hours or darunavir/cobicistat 1 tablet per day) and hidrossycloroquine 400 mg every 12 hours then first day, followed by 200 mg every 12 hours for other 4 days.

Group Type NO_INTERVENTION

No interventions assigned to this group

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

Medical Ozone procedure

The systemic ozone treatment procedure was decided by the physician on duty and started preliminarily at the patient's bed with the drawing of autologous blood and, after proper O2/O3 mixing, with its re-infusion. After junction of an adequate venous patient's way with a dedicated latex free plastic bag containing 35 ml of sodium citrate, a blood amount of 200 ml is taken. At the end, the withdrawal line was washed and the re-infusion one was filled with saline solution. The blood, without any patient disconnection, was then mixed with a gas mixture of a 200 cc composed by 96% of Oxygen and 4% of Ozone with a therapeutic O3 range of 40 μg/mL of gas per mL of blood. In order to guarantee the O2/O3 homogeneous diffusion into the blood, the bag was gently mixed for about 10 minutes, therefore the blood was re-infused into the patients. The duration of ozone treatment lasted for 3 consecutive days.

Intervention Type PROCEDURE

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

Inclusion Criteria

* Male and no pregnant female patients 18 years of age or older were eligible if they had a diagnostic specimen that was positive on RT-PCR, had pneumonia confirmed by chest imaging and gave their informed consent to participate at the study
Minimum Eligible Age

18 Years

Maximum Eligible Age

99 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

Fondazione Toscana Gabriele Monasterio

OTHER

Sponsor Role collaborator

Policlinico Militare, Roma - Italy

UNKNOWN

Sponsor Role collaborator

Ospedale San Liberatore di Atri

UNKNOWN

Sponsor Role collaborator

Ospedale Umberto I di Torino

OTHER

Sponsor Role collaborator

Università di Siena

UNKNOWN

Sponsor Role collaborator

Ospedale Civile di Lucca

UNKNOWN

Sponsor Role collaborator

Ospedale di Siracusa

UNKNOWN

Sponsor Role collaborator

Azienda Sanitaria Locale di Vercelli

OTHER

Sponsor Role collaborator

Azienda Sanitaria-Universitaria Integrata di Udine

OTHER

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Carlo Tascini

Infectious Diseases Department

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

Amato De Monte

Role: STUDY_CHAIR

Presidio Ospedaliero Universitario "Santa Maria della Misericordia", Udine - Italy

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

Dott. Amato De Monte

Udine, , Italy

Site Status RECRUITING

Countries

Review the countries where the study has at least one active or historical site.

Italy

Central Contacts

Reach out to these primary contacts for questions about participation or study logistics.

Carlo Tascini, MD

Role: CONTACT

+39 0432 559355

Emanuela Sozio, MD

Role: CONTACT

Facility Contacts

Find local site contact details for specific facilities participating in the trial.

Amato De Monte, MD

Role: primary

References

Explore related publications, articles, or registry entries linked to this study.

Cao B, Wang Y, Wen D, Liu W, Wang J, Fan G, Ruan L, Song B, Cai Y, Wei M, Li X, Xia J, Chen N, Xiang J, Yu T, Bai T, Xie X, Zhang L, Li C, Yuan Y, Chen H, Li H, Huang H, Tu S, Gong F, Liu Y, Wei Y, Dong C, Zhou F, Gu X, Xu J, Liu Z, Zhang Y, Li H, Shang L, Wang K, Li K, Zhou X, Dong X, Qu Z, Lu S, Hu X, Ruan S, Luo S, Wu J, Peng L, Cheng F, Pan L, Zou J, Jia C, Wang J, Liu X, Wang S, Wu X, Ge Q, He J, Zhan H, Qiu F, Guo L, Huang C, Jaki T, Hayden FG, Horby PW, Zhang D, Wang C. A Trial of Lopinavir-Ritonavir in Adults Hospitalized with Severe Covid-19. N Engl J Med. 2020 May 7;382(19):1787-1799. doi: 10.1056/NEJMoa2001282. Epub 2020 Mar 18.

Reference Type BACKGROUND
PMID: 32187464 (View on PubMed)

Elvis AM, Ekta JS. Ozone therapy: A clinical review. J Nat Sci Biol Med. 2011 Jan;2(1):66-70. doi: 10.4103/0976-9668.82319.

Reference Type BACKGROUND
PMID: 22470237 (View on PubMed)

Bocci VA. Scientific and medical aspects of ozone therapy. State of the art. Arch Med Res. 2006 May;37(4):425-35. doi: 10.1016/j.arcmed.2005.08.006.

Reference Type BACKGROUND
PMID: 16624639 (View on PubMed)

Smith NL, Wilson AL, Gandhi J, Vatsia S, Khan SA. Ozone therapy: an overview of pharmacodynamics, current research, and clinical utility. Med Gas Res. 2017 Oct 17;7(3):212-219. doi: 10.4103/2045-9912.215752. eCollection 2017 Jul-Sep.

Reference Type BACKGROUND
PMID: 29152215 (View on PubMed)

Gulmen S, Kurtoglu T, Meteoglu I, Kaya S, Okutan H. Ozone therapy as an adjunct to vancomycin enhances bacterial elimination in methicillin resistant Staphylococcus aureus mediastinitis. J Surg Res. 2013 Nov;185(1):64-9. doi: 10.1016/j.jss.2013.05.085. Epub 2013 Jun 19.

Reference Type BACKGROUND
PMID: 23809152 (View on PubMed)

Provided Documents

Download supplemental materials such as informed consent forms, study protocols, or participant manuals.

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Related Links

Access external resources that provide additional context or updates about the study.

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

CIG: Z7C2CA5837

Identifier Type: -

Identifier Source: org_study_id

More Related Trials

Additional clinical trials that may be relevant based on similarity analysis.

Functional Implications of TNF
NCT00729131 COMPLETED
ORCHARDS-AIR Study
NCT07298967 RECRUITING NA