Molecular hydrogen for outpatients with Covid-19 (Hydro-Covid): a phase 3, randomised, triple-blinded, adaptive, placebo-controlled, multicentre trial

BackgroundDue to its antioxidative, anti-inflammatory, anti-apoptosis, and antifatigue properties, molecular hydrogen (H2) is potentially a novel therapeutic gas for acute coronavirus disease 2019 (COVID-19) patients. AimTo determine the efficacy and safety profile of hydrogen rich water (HRW) to reduce the risk of progression of COVID-19. Design and settingsWe conducted a phase 3, triple-blind, randomized, placebo-controlled trial to evaluate treatment with HRW started within 5 days after the onset of signs or symptoms in primary care patients with mild-to-moderate, laboratory-confirmed COVID-19 and at least one risk factor for severe COVID-19 illness. MethodParticipants were randomly assigned to receive HRW or placebo twice daily for 21 days. The composite primary endpoint was the incidence of clinical worsening (dyspnea, fatigue) associated with a need for oxygen therapy, hospitalization or death at day-14; the incidence of adverse events was the primary safety end point. ResultsA total of 675 participants were followed up until day-30. 337 in the HRW group and 338 in the placebo group. Baseline characteristics were similar in the two groups. HRW was not superior to placebo in preventing clinical worsening at day-14: in H2 group, 46.1% met a clinical deterioration, 43.5% in the placebo group, Hazard Ratio 1.09, 90% confidence interval [0.90-1.31]. One death was reported in the H2 group and 2 in the placebo group at day-30. Adverse events were reported in 91 (27%) and 89 (26.2%) participants respectively. ConclusionTwice-daily ingestion of HRW from the onset of COVID-19 symptoms for 21 days did not reduce clinical worsening. How this fits inO_LIOnly a few molecules specially developed against SARS-CoV-2 can limit impact of COVID-19 (vaccines, monoclonal antibodies or antiviral drugs) C_LIO_LIUsing their multiple properties, H2 may play a key role in preventing the severe and post-acute forms of COVID-19 C_LIO_LITaking twice daily Hydrogen Rich Water (HRW) was not efficacious to prevent severe COVID-19 in at risk COVID-19 patients. C_LIO_LIHRW confirmed a very safe profil C_LI