METHYLENE BLUE FOR TREATMENT OF HOSPITALIZED COVID-19 PATIENTS: A RANDOMIZED, CONTROLLED, OPEN-LABEL CLINICAL TRIAL, PHASE 2

Background: There is no pharmacological intervention on the treatment of hypoxemia and respiratory distress in COVID-19 patients.

Objective: The objective of the study was to study the effect of the reduced form of methylene blue (MB) on the improvement of oxygen saturation (SpO₂) and respiratory rate (RR).

Methods: In an academic medical center, 80 hospitalized patients with severe COVID-19 were randomly assigned to receive either oral MB along with standard of care (SOC) (MB group, n = 40) or SOC only (SOC group, n=40). The primary outcomes were SpO₂ and RR on the 3^rd and 5^th days. The secondary outcomes were hospital stay and mortality within 28 days.

Results: In the MB group, a significant improvement in SpO₂ and RR was observed on the 3^rd day (for both, p < 0.0001) and also the 5^th day (for both, p < 0.0001). In the SOC group, there was no significant improvement in SpO₂ (p = 0.24) and RR (p = 0.20) on the 3^rd day, although there was a significant improvement of SpO₂ (p = 0.002) and RR (p = 0.01) on the 5^th day. In the MB group in comparison to the SOC group, the rate ratio of increased SpO₂ was 13.5 and 2.1 times on the 3^rd and 5^th days, respectively. In the MB group compared with the SOC group, the rate ratio of RR improvement was 10.1 and 3.7 times on the 3^rd and 5^th days, respectively. The hospital stay was significantly shortened in the MB group (p = 0.004), and the mortality was 12.5% and 22.5% in the MB and SOC groups, respectively.

Conclusions: The addition of MB to the treatment protocols significantly improved SpO₂ and respiratory distress in COVID-19 patients, which resulted in decreased hospital stay and mortality. ClinicalTrials.gov: NCT04370288.