SARS-CoV-2 Respiratory Failure
Conditions
Keywords
SARS-CoV-2, Respiratory Failure, COVID-19, medical ozone, ozone therapy, cytokine release syndrome
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.
Interventions
PROCEDUREMedical 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.
Sponsors
Fondazione Toscana Gabriele Monasterio
Policlinico Militare, Roma - Italy
Ospedale San Liberatore di Atri
Ospedale Umberto I di Torino
Università di Siena
Ospedale Civile di Lucca
Ospedale di Siracusa
Azienda Sanitaria Locale di Vercelli
Azienda Sanitaria-Universitaria Integrata di Udine
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Investigator)
Masking description
Randomization, 1:1 ratio
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
Eligibility
Sex/Gender
ALL
Age
18 Years to 99 Years
Healthy volunteers
No
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
*
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The time of respiratory improvement and earlier weaning from oxygen support | 10 days | Evaluation of ABG paramethers the one week after the last blood ozonization procedure (Day 10) |
| Time of respiratory improvement and earlier weaning from oxygen support | 3 days | Evaluation of ABG paramethers the day after the last blood ozonization procedure (Day 3) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Assessment of the length of hospitalization | up to 90 days | Asse the lenghth of hospital stay in the two arms |
| Assessment of the length of Intensive Care Unit (ICU) stay | up to 90 days | Asse the lenghth of ICU stay in the two arms |
| Improvment in chest imaging finding | 10 days | improving, worsening or stability of the chest imaging (chest CT, Chest XR and/or Point-of-Care Ultrasound) finding in the two arms |
| Improvment in cytokine release syndrome | 10 days | Evaluation of plasmatic cytochine (IL-6, lymphocyte typing for CD4, CD3, CD8, HLA-DR, CD45) response in the two arms |
Countries
Italy
Contacts
Primary ContactCarlo Tascini, MD
Backup ContactEmanuela Sozio, MD
Outcome results
None listed