Methylene blue for treatment of hospitalized COVID-19 patients: a randomized, controlled, open-label clinical trial, phase 2

Hamidi-Alamdari et al., Clinical and Translational Investigation, doi:10.24875/RIC.21000028, NCT04370288, Mar 2021
Mortality 44% improvement lower risk ← → higher risk Hospitalization time 38% Vitamin C  Hamidi-Alamdari et al.  LATE TREATMENT RCT Is late treatment with vitamin C + combined treatments beneficial? RCT 80 patients in Iran (April - September 2020) Shorter hospitalization with treatment (p=0.004) c19early.org Hamidi-Alamdari et al., Clinical and T.., Mar 2021 0 0.5 1 1.5 2+ RR
Vitamin C for COVID-19
6th treatment shown to reduce risk in September 2020, now with p = 0.00000002 from 75 studies, recognized in 22 countries.
Lower risk for mortality, ICU, hospitalization, and recovery.
No treatment is 100% effective. Protocols combine treatments.
6,200+ studies for 200+ treatments. c19early.org
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RCT 80 hospitalized patients with severe COVID-19, 40 treated with methylene blue + vitamin C + N-acetylcysteine, showing lower mortality, shorter hospitalization, and significantly improved SpO2 and respiratory distress with treatment.
This is the 6th of 21 COVID-19 RCTs for vitamin C, which collectively show efficacy with p=0.0012.
This is the 16th of 75 COVID-19 controlled studies for vitamin C, which collectively show efficacy with p=0.00000002 (1 in 50 million).
Important missing comments or errors? Let us know.
risk of death, 44.4% lower, RR 0.56, p = 0.38, treatment 5 of 40 (12.5%), control 9 of 40 (22.5%), NNT 10.0.
hospitalization time, 37.6% lower, relative time 0.62, p = 0.004, treatment 40, control 40.
Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates
Hamidi-Alamdari et al., 8 Mar 2021, Randomized Controlled Trial, Iran, peer-reviewed, 23 authors, study period 19 April, 2020 - 21 September, 2020, this trial uses multiple treatments in the treatment arm (combined with methylene blue and N-acetyl cysteine) - results of individual treatments may vary, trial NCT04370288 (history).
$0 $500 $1,000+ Efficacy vs. cost for COVID-19 treatment protocols c19early.org November 2025 Iran United Kingdom Russia USA Sudan Angola Colombia Kenya Mozambique Pakistan Argentina Vietnam Peru Philippines Spain Brazil Italy France Japan China Uzbekistan Nepal Ethiopia Ghana Mexico South Korea Germany Bangladesh Saudi Arabia Algeria Morocco Yemen Poland India DR Congo Madagascar Thailand Uganda Venezuela Nigeria Egypt Bolivia Taiwan Zambia Fiji Bosnia-Herzegovina Ukraine Côte d'Ivoire Bulgaria Greece Slovakia Singapore Iceland New Zealand Czechia Mongolia Israel Trinidad and Tobago Hong Kong North Macedonia Belarus Qatar Panama Serbia CAR Iran favored high-profit treatments.The average efficacy of treatments was moderate.High-cost protocols reduce early treatment, andforgo complementary/synergistic benefits. More effective More expensive 75% 50% 25% ≤0%
$0 $500 $1,000+ Efficacy vs. cost for COVID-19treatment protocols worldwide c19early.org November 2025 Iran United Kingdom Russia USA Sudan Angola Colombia Kenya Mozambique Pakistan Argentina Vietnam Peru Philippines Spain Brazil Italy France Japan China Uzbekistan Nepal Ethiopia Ghana Mexico South Korea Germany Bangladesh Saudi Arabia Algeria Morocco Yemen Poland India DR Congo Madagascar Thailand Uganda Venezuela Nigeria Egypt Bolivia Taiwan Zambia Fiji Bosnia-Herzegovina Côte d'Ivoire Bulgaria Greece Slovakia Malawi Czechia Mongolia Israel Trinidad and Tobago North Macedonia Belarus Qatar Panama Serbia Syria Iran favored high-profit treatments.The average efficacy was moderate.High-cost protocols reduce early treatment,and forgo complementary/synergistic benefits. More effective More expensive 75% 50% 25% ≤0%
Methylene Blue for Treatment of Hospitalized COVID-19 Patients: A Randomized, Controlled, Open-Label Clinical Trial, Phase 2
Daryoush Hamidi-Alamdari, Saied Hafizi-Lotfabadi, Ahmad Bagheri-Moghaddam, Hossin Safari, Mahnaz Mozdourian, Zahra Javidarabshahi, Arash Peivandi-Yazdi, Abass Ali-Zeraati, Alireza Sedaghat, Farid Poursadegh, Fatemeh Barazandeh-Ahmadabadi, Marzieh Agheli-Rad, Seyed M Tavousi, Shohreh Vojouhi, Shahram Amini, Mahnaz Amini, Seyed Majid-Hosseini, Ashraf Tavanaee-Sani, Amin Ghiabi, Shima Nabavi-Mahalli, Negar Morovatdar, Omid Rajabi, George Koliakos
Revista de investigaci�n Cl�nica, 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 (SpO 2 ) 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 SpO 2 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 SpO 2 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 SpO 2 (p = 0.24) and RR (p = 0.20) on the 3 rd day, although there was a significant improvement of SpO 2 (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 SpO 2 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 SpO 2 and respiratory distress in COVID-19 patients, which resulted in decreased hospital stay and mortality. ClinicalTrials.gov: NCT04370288 (REV INVEST CLIN. 2021;73(3):XX-XX)
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Late treatment
is less effective
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