ABSTRACT
BackgroundPassive immunotherapy with convalescent plasma (CP) is a potential treatment for COVID-19 for which evidence from controlled clinical trials is lacking. MethodsWe conducted a multi-center, randomized clinical trial in patients hospitalized for COVID-19. All patients received standard of care treatment, including off-label use of marketed medicines, and were randomized 1:1 to receive one dose (250-300 mL) of CP from donors with IgG anti-SARS-CoV-2. The primary endpoint was the proportion of patients in categories 5, 6 or 7 of the COVID-19 ordinal scale at day 15. ResultsThe trial was stopped after first interim analysis due to the fall in recruitment related to pandemic control. With 81 patients randomized, there were no patients progressing to mechanical ventilation or death among the 38 patients assigned to receive plasma (0%) versus 6 out of 43 patients (14%) progressing in control arm. Mortality rates were 0% vs 9.3% at days 15 and 29 for the active and control groups, respectively. No significant differences were found in secondary endpoints. At inclusion, patients had a median time of 8 days (IQR, 6-9) of symptoms and 49,4% of them were positive for anti-SARS-CoV-2 IgG antibodies. ConclusionsConvalescent plasma could be superior to standard of care in avoiding progression to mechanical ventilation or death in hospitalized patients with COVID-19. The strong dependence of results on a limited number of events in the control group prevents drawing firm conclusions about CP efficacy from this trial. (Funded by Instituto de Salud Carlos III; NCT04345523).
ABSTRACT
Objectives. To evaluate the efficacy and safety of switching from a selective serotonin reuptake inhibitor (SSRI) to duloxetine in non- or partial responders. Methods. This is a post-hoc analysis of the pooled data of the Spanish sample from an open-label, multicentre study. Additionally, a 6-month continuation safety phase was performed. Results. A total of 156 patients were switched to duloxetine from SSRIs. More than 83% completed the acute phase, of whom 75% went into the continuation phase. At baseline, the mean duration of SSRI treatment was 71.2 weeks and the HAM-D17 mean score was 22.4. In the acute-phase, symptoms severity significantly improved after 10 weeks of duloxetine treatment as measured by mean change from baseline in HAM-D17 total score (-10.5; P<0.001) and all secondary efficacy measures, including painful symptoms. Response (≥50% decrease in HAM-D17 total score) and remission rates (HAM-D17 total score ≤ 7) were 52.9 and 27.7%, respectively. The most common adverse events reported in both phases were headache (11.5% [acute]; 6.1% [continuation]) and nausea (6.4% [acute]; 5.1% [continuation]). Conclusions. In a population of Spanish SSRI non- and partial responders, switch to duloxetine was associated with significant improvement in emotional and painful symptoms of depression. Duloxetine was well tolerated and safe during both phases.
