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

SARS-CoV-2 Respiratory Failure Clinical Trial

— CORMOR  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04388514
• Other study ID #: CIG: Z7C2CA5837
• Status: Recruiting
• Phase: N/A
• Start date: April 8, 2020
• Est. completion date: October 8, 2020

Study information

• Verified date: May 2020
• Source: Azienda Sanitaria-Universitaria Integrata di Udine
• Contact: Carlo Tascini, MD
• Phone: +39 0432 559355
• Email: c.tascini[@]gmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 90
• Est. completion date: October 8, 2020
• Est. primary completion date: October 8, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 99 Years

Eligibility

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.

Related Conditions & MeSH terms

• Respiratory Insufficiency
• SARS-CoV-2 Respiratory Failure

Intervention

Procedure:
• 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.

Locations

Country	Name	City	State
Italy	Dott. Amato De Monte	Udine

Sponsors (9)

Lead Sponsor	Collaborator
Azienda Sanitaria-Universitaria Integrata di Udine	Azienda Sanitaria Locale di Vercelli, Fondazione Toscana Gabriele Monasterio, Ospedale Civile di Lucca, Ospedale di Siracusa, Ospedale San Liberatore di Atri, Ospedale Umberto I di Torino, Policlinico Militare, Roma - Italy, Università di Siena

Country where clinical trial is conducted

Italy, 

References & Publications (5)

Bocci VA. Scientific and medical aspects of ozone therapy. State of the art. Arch Med Res. 2006 May;37(4):425-35. Review. — View 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. — View 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. — View 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. — View 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. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Time of respiratory improvement and earlier weaning from oxygen support	Evaluation of ABG paramethers the day after the last blood ozonization procedure (Day 3)	3 days
Primary	The time of respiratory improvement and earlier weaning from oxygen support	Evaluation of ABG paramethers the one week after the last blood ozonization procedure (Day 10)	10 days
Secondary	Assessment of the length of hospitalization	Asse the lenghth of hospital stay in the two arms	up to 90 days
Secondary	Assessment of the length of Intensive Care Unit (ICU) stay	Asse the lenghth of ICU stay in the two arms	up to 90 days
Secondary	Improvment in chest imaging finding	improving, worsening or stability of the chest imaging (chest CT, Chest XR and/or Point-of-Care Ultrasound) finding in the two arms	10 days
Secondary	Improvment in cytokine release syndrome	Evaluation of plasmatic cytochine (IL-6, lymphocyte typing for CD4, CD3, CD8, HLA-DR, CD45) response in the two arms	10 days

External Links

•   doi: 10.4081/ozone.2020.9014.
•   SIMEU Classification and Guidelines