CORonavirus-19 mild to moderate pneumonia Management with blood Ozonization in patients with Respiratory failure (CORMOR) multicentric prospective randomized clinical trial

Abstract

Background: Following positive experience on the use of blood ozonation in SARS-CoV-2, the CORMOR randomized trial was designed to evaluate the adjuvant role of oxygen/ozone therapy in mild to moderate SARS-CoV-2 pneumonia.

Methods: The trial (ClinicalTrial.gov NCT04388514) was conducted in four different Italian centers (April-October 2020). Patients were treated according to best available standard of care (SoC) therapy, with or without O3-autohemotherapy (O3-AHT).

Results: A total of 92 patients were enrolled: SoC + O3-AHT (48 patients) were compared to the SoC treatment (44 patients). The two groups differed in steroids therapy administration (72.7% in SoC arm vs. 50.0% in O3-AHT arm; p = 0.044). Steroid therapy was routinely started when it was subsequently deemed as effective for the treatment of COVID-19 disease. No significant differences in mortality rates, length of hospital stay, mechanical ventilation requirement and ICU admission were observed. Clinical improvement in patients with pneumonia was assessed according to a specifically designed score (decrease in SIMEU class, improvement in radiology imaging, improvement in PaO2/FiO2, reduction in LDH and requirement of oxygen therapy ≤ 5 days). Score assessment was performed on day-3 (T3) and day-7 (TEnd) of O3-AHT treatment. A significant increase in the score was reported at TEnd, in the O3-AHT treatment arm (0 [0-1] in the SoC arm vs. 2 [1-3] the O3-AHT arm; p = 0.018). No adverse events related O3-AHT treatment was observed.

Conclusion: In mild-to-moderate pneumonia due to SARS-CoV-2, adjuvant oxygen/ozone therapy did not show any effect on mortality, or mechanical intubation but show a clinical improvement a day 7 from randomization in a composite clinical endpoint. Larger Randomized prospective studies alone or in combination with steroids are needed to confirm our results.

Keywords: Autotransfusion; COVID-19; Cytokine release syndrome; Medical ozone; Ozone gas; Ozone therapy; SARS-CoV-2.

Fig. 1

Flow chart of CORMOR study. Legend: ICU: intensive care unit. Standard of Care – Lopinavir/Ritonavir 200/50 mg 2 tablets every 12 h or Darunavir/Cobicistat 800/150 mg 1 tablet per day; Hydroxychloroquine 400 mg every 12 h on the first day, followed by 200 mg every 12 h for the following 4 days; Dexamethasone 6 mg once daily for up to 10 days (see Table 3 for detail).

Fig. 2

Pulmonary improvement score evaluated at T₃ (Panel A) and at T_End (Panel B). Legend: At T₃ the Pulmonary improvement score was evaluated as improvement of SIMEU class, presence of radiological improvement, 10% improvement in the PaO₂/FiO₂ ratio, 10% reduction in LDH concentration (score from 0 to 4). At T_End the Pulmonary improvement score was evaluated as improvement of SIMEU class, presence of radiological improvement, 10% improvement in the PaO₂/FiO₂ ratio, 10% reduction in LDH concentration and length of oxygen therapy < 5 days (score from 0 to 5).