Discussion
COVID-19 disease, COVID-19 infected
ADVERSE EVENTS, EVENTS, DISEASE, VIRUS
This clinical trial explored the antiviral activity in the clinical practice of an already marketed product, domperidone, as drug repositioning for COVID-19 treatment. As main result, no significant differences were observed in the evolution of the viral load nor in the symptoms frequency or severity comparing domperidone versus placebo in the 28 days of follow-up.It has been reported that COVID-19 vaccine can effectively reduce the mortality of COVID-19 infected patients [Recently, three oral drugs have shown effective results in clinical trials for COVID-19: molnupiravir, fluvoxamine and Paxlovid. A meta-analysis of the published data [Our group investigated the efficacy of bromhexine as repurposing treatment for COVID-19 compared to SOC group in an open-label phase III clinical trial. The study design and primary care setting were common with the trial presented in this report to facilitate the results comparisons, except the double-blind design that was feasible in the present study that avoided bias in the concomitant medications use. The conclusion was that bromhexine did not offer advantages in the treatment of patients with mild-to-moderate COVID-19 [In this randomized double-blind clinical trial, domperidone was compared with placebo. A total of 173 patients were included, being 63% women, ant the mean age of the patients was of 47.8 years. This figure is consistent with global data recorded in Spain for patients with COVID-19, resulting the patients in the age range of 50–69 years the most affected during the pandemic, 55% of them were women [It was remarkable the wide range of symptoms, observing up to 20 symptoms in one patient, and the already known variety of system organ class related (Overall baseline data, including vital signs and symptom distribution, were similar in the two study groups, making them comparable (Viral load at baseline was similar in the two study groups as well as the percentages of patients with low, medium and high viral loads. We observe great proportion of patient with high viral load, up to 75.9% for the domperidone group and 81.4% for the placebo group. It was notable that at day 14, 30% of the patients were still positive, although the viral load was low (22%), or medium (6.9%), but still high in 1.2%. We observed the lack of differences between the study groups in the evolution of vital signs, overall improvement of severity of symptoms and percentage of patients with persistent symptoms after day 28.It was not possible to translate from Ct values to number of viral copies, in consequence the viral loads comparison was not feasible. Regarding the primary efficacy endpoint of as was the reduction in the viral load from baseline-day 4, no differences were found between the domperidone versus placebo patient’s groups for the specific genes of the SARS-CoV-2 pathogenic viral RNA strain. Statistically significant reductions in viral loads were found from baseline for the total study population, but without differences between the study groups. Moreover, the percentage of patients with positive RT-qPCR results at days 4, 7 and 14 and the proportion of patients classified by viral load degree were similar in the two study groups.In terms of safety outcome, few patients reported adverse events, and there were no significant differences between the study groups. Almost all adverse events were mild and not related to treatment. Eight adverse events in the placebo group and two adverse events in the domperidone group lead to discontinuation of the study drug but no patients needed to be hospitalized due to the COVID-19 disease.The double-blind design is a strength of the study. The effect of domperidone on the evolution of symptoms could not be properly evaluated due to the limited sample size and the wide range of symptoms observed in patients with COVID-19, but no differences were observed. The increasement of prolactine levels occur with the doses of domperidone used in the study assuring the effects described in the introduction but could not be measured for this trial. We observed limitations due to distant communication and difficulty interpreting the symptoms severity by the patients and physicians. In addition, the study size did not allow the evaluation of the effect on hospitalization rates nor mortality, considering that the patients included in the study with mild-to-moderate COVID-19 had lower hospitalization and mortality risk. The inclusion of 96% patients with mild disease where almost all cure spontaneously limited the observation of risk events. With the inclusion of more moderate cases perhaps differences between treatment groups might be observed. It is unknown if the effect of domperidone could be different as per virus variant.