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] , [2] , [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.

Ozone as an adjuvant therapy for COVID-19: A systematic review and meta-analysis

“…1 ) . Three RCTs [23] , [25] , [26] were considered to be in high-quality studies and an RCT [24] had some concerns according to Cochrane’s Risk of Bias 2 (RoB2) assessment (Table S2) . Robins-I assessment determined that a clinical trial had a moderate risk of bias [22] (Table S3) .…”

“…In this review, the majority were observational studies (4 case-control studies, and 4 case-series) conducted in Spain [19] , [20] , [29] , Italy [18] , [28] , Turkey [21] , Egypt [27] , and China [30] . In addition, there is one clinical trial from India [22] , and four RCTs conducted in Italy [23] , [24] , India [25] and Turkey [26] . Based on the administration route, eight studies were conducted using major autohemotherapy [18] , [19] , [21] , [22] , [23] , [25] , [28] , [29] , two studies using rectal insufflation [19] , [27] , and one study using intravenous ozonated saline [22] , one study using ozone nebulization [26] and one study using the combination of minor autohemotherapy and rectal insufflation [25] .…”

“…In addition, there is one clinical trial from India [22] , and four RCTs conducted in Italy [23] , [24] , India [25] and Turkey [26] . Based on the administration route, eight studies were conducted using major autohemotherapy [18] , [19] , [21] , [22] , [23] , [25] , [28] , [29] , two studies using rectal insufflation [19] , [27] , and one study using intravenous ozonated saline [22] , one study using ozone nebulization [26] and one study using the combination of minor autohemotherapy and rectal insufflation [25] . Standard therapy consists of corticosteroids, antivirals (lopinavir, ritonavir, remdesivir), antibiotics (such as azithromycin), and vitamin supplements (vitamin E, vitamin C, vitamin D, and zinc) [18] , [19] , [20] , [21] , [22] , [23] , [24] , [25] , [26] , [27] , [28] , [29] , [30] .…”

The Relationship between Ozone and Human Blood in the Course of a Well-Controlled, Mild, and Transitory Oxidative Eustress

“…The therapeutic potential of this treatment is recognizable from the numerous clinical trials (Table 1), some of which are currently available in the literature, especially for COVID-19 treatments [51][52][53]. Moreover, several pilots, but crucial clinical reports in chronic limb ischemia [54,55], age-related macular degeneration [56], chronic obstructive pulmonary disease [57], have already shown the effectiveness of ozone therapy making clear that the ozone dosage must be adequately adjusted.…”

“…The therapeutic potential of this treatment is recognizable from the numerous clinical trials ( Table 1 ), some of which are currently available in the literature, especially for COVID-19 treatments [ 51 , 52 , 53 ].…”