COVID-19 Evidence Alerts
from McMaster PLUSTM

Current best evidence for clinical care (more info)

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Treatment Hamidi-Alamdari D, Hafizi-Lotfabadi S, Bagheri-Moghaddam A, et al. METHYLENE BLUE FOR TREATMENT OF HOSPITALIZED COVID-19 PATIENTS: A RANDOMIZED, CONTROLLED, OPEN-LABEL CLINICAL TRIAL, PHASE 2. Rev Invest Clin. 2021;73(3):190-198. doi: 10.24875/RIC.21000028.

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 3rd and 5th 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 3rd day (for both, p < 0.0001) and also the 5th 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 3rd day, although there was a significant improvement of SpO2 (p = 0.002) and RR (p = 0.01) on the 5th 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 3rd and 5th 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 3rd and 5th 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. NCT04370288.

Discipline / Specialty Area Score
Hospital Doctor/Hospitalists
Internal Medicine
Infectious Disease
Intensivist/Critical Care
Comments from MORE raters

Hospital Doctor/Hospitalists rater

In this trial, the authors (for whom it is not clear have direct connection to the patent they are testing) trial an oral formulation of methylene blue for patients with COVID-19. They list their trial on; on that site, they say that the formulation will be given IV, and the primary outcome will be intubation. Somehow intubation is not even reported in this paper, but oxygen SATURATION on room air becomes the primary outcome; the thoughts of patients sitting without oxygen with saturations in the 70's while someone awaits a baseline seems quite scary to me, and lack of reliance on a harder outcome such as blood gas seems quite questionable. The bottom line: I can't trust this result. It probably never should have been published; if you have COVID-19 and you're passing this hospital, keep driving...

Infectious Disease rater

This is interesting but preliminary. In addition to several issues of potential biases and inaccurate analysis, the sample size and the primary outcomes limit any clinically useful conclusion.

Intensivist/Critical Care rater

The sample size is small, but the results are encouraging. The sample size needs to be expanded to confirm benefits.

Internal Medicine rater

In a small group of hospitalized patients with severe COVID-19 pneumonia, the authors showed improved oxygenation and symptom control at day 3 and day 5 of administration of methylene blue compared with no methylene blue. this is very interesting. These hypothesis generating results need further research in this direction.

Internal Medicine rater

Although this study would best be classified as preliminary, the results are astounding and require rapid confirmation with a proper RCT.

Respirology/Pulmonology rater

Despite its limitations, it is a well-designed study, with promising results.