Clinical trial NCT04388514: Blood Ozonization in Patients With SARS-CoV-2 Respiratory Failure
Official title: Blood Ozonization in Patients With SARS-CoV-2 Respiratory Failure
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: SARS-CoV-2 Respiratory Failure
Keywords: SARS-CoV-2
Respiratory Failure
COVID-19
medical ozone
ozone therapy
cytokine release syndrome
Lead sponsor: Azienda Sanitaria-Universitaria Integrata di Udine
Sponsor class: OTHER
Collaborators: name: Fondazione Toscana Gabriele Monasterio
name: Policlinico Militare, Roma - Italy
name: Ospedale San Liberatore di Atri
name: Ospedale Umberto I di Torino
name: Università di Siena
name: Ospedale Civile di Lucca
name: Ospedale di Siracusa
name: Azienda Sanitaria Locale di Vercelli
First posted: 2020-05-14
Enrollment: 90
Sex: ALL
Minimum age (years): 18
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: 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 purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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

Exclusion Criteria:

* Exclusion criteria were pregnancy, G6PHD (glucose 6 phosphate dehydrogenase) deficiency, concomitant serious disease and failure to obtain informed consent.

Primary outcomes:
measure: Time of respiratory improvement and earlier weaning from oxygen support
timeFrame: 3 days
measure: The time of respiratory improvement and earlier weaning from oxygen support
timeFrame: 10 days
Secondary outcomes:
measure: Assessment of the length of hospitalization
timeFrame: up to 90 days
measure: Assessment of the length of Intensive Care Unit (ICU) stay
timeFrame: up to 90 days
measure: Improvment in chest imaging finding
timeFrame: 10 days
measure: Improvment in cytokine release syndrome
timeFrame: 10 days
Other outcomes:
Locations:
city: Udine
country: Italy
facility: Dott. Amato De Monte
Study officials:
affiliation: Presidio Ospedaliero Universitario "Santa Maria della Misericordia", Udine - Italy
name: Amato De Monte
role: STUDY_CHAIR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.