In the initial phase of COVID-19 infection both Hydroxychloroquine and chloroquine, two old drugs with multiple indications were used as a treatment approach for COVID-19 infection. The clear indication for the above drugs was lacking strong published evidence. Most of the supported trials were small or/and lacking proper design. In the current study an adequate number of patients was randomized using a randomized, controlled, open-label platform trial. Patients were assigned to receive either hydroxychloroquine or usual care. The dose in the hydroxychloroquine group was 800mg at baseline followed by 400mg twice a day for the next 9 days or until discharge if the latter occurred earlier.
The primary outcome was 28-day mortality. Secondary outcomes were attributed to hospital stay, the use of invasive mechanical ventilation including ECMO. Safety data, mainly in terms of cardiac arrhythmias, was recorded. Of the eligible patients to receive hydroxychloroquine, 1561 were assigned to receive hydroxychloroquine and 3155 were assigned to receive usual care. Mean age was 62 years old, 61% males, 16% received mechanical ventilation. Regarding concomitant diseases an equal distribution of chronic lung diseases, diabetes and heart diseases was observed [20% for each]. The median duration of treatment was 6 days.
Death at 28 days occurred in 421 of 1561 patients (27.0%) in the hydroxychloroquine group and in 790 of 3155 patients (25.0%) in the usual-care group and was irrespective of a pre positive test for SARS COV2. The duration of hospitalization was longer in the hydroxychloroquine group, while among patients who did not receive invasive mechanical ventilation at baseline, the use of invasive ventilation was higher in the hydroxychloroquine group. Regarding safety issues focusing on cardiac arrhythmias the incidence was low and with no difference between the two arms.
The trial is negative and raises significant concerns for treatment approaches, when clinical and publishing data are not supportive.