RESUMEN
BACKGROUND: Algae-derived nutraceuticals, such as spirulina, have been reported to have biological activities that may minimize clinical consequences to COVID-19 infections. OBJECTIVES: This study aimed to determine whether spirulina is an effective treatment for high-risk patients with early COVID-19 in an outpatient setting. METHODS: The TOGETHER trial is a placebo-controlled, randomized, platform trial conducted in Brazil. Eligible participants were symptomatic adults with a positive rapid test for SARS-CoV-2 older than 50 y or with a known risk factor for disease severity. Patients were randomly assigned to receive placebo or spirulina (1 g twice daily for 14 d). The primary end point was hospitalization defined as either retention in a COVID-19 emergency setting for >6 h or transfer to tertiary hospital owing to COVID-19 at 28 d. Secondary outcomes included time-to-hospitalization, mortality, and adverse drug reactions. We used a Bayesian framework to compare spirulina with placebo. RESULTS: We recruited 1126 participants, 569 randomly assigned to spirulina and 557 to placebo. The median age was 49.0 y, and 65.3% were female. The primary outcome occurred in 11.2% in the spirulina group and 8.1% in the placebo group (odds ratio [OR]: 1.24; 95% credible interval: 0.84, 1.86). There were no differences in emergency department visit (OR: 1.21; 95% credible interval: 0.81, 1.83), nor time to symptom relief (hazard ratio: 0.90; 95% credible interval: 0.79, 1.03). Spirulina also not demonstrate important treatment effects in the prespecified subgroups defined by age, sex, BMI, days since symptom onset, or vaccination status. CONCLUSIONS: Spirulina has no any clinical benefits as an outpatient therapy for COVID-19 compared with placebo with respect to reducing the retention in an emergency setting or COVID-19-related hospitalization. There are no differences between spirulina and placebo for other secondary outcomes. This trial was registered at clinicaltrials.gov as NCT04727424.