ABSTRACT
Background: COVID19 complications cause inflammatory storm. Colchicine is a potent anti-inflammatory medication that has been proposed as a possible treatment option for COVID-19. Objective: to assess effectiveness and safety of add on use of colchicine to the standard treatment in moderate and severe COVID-19. Patients and methods: In this randomized controlled open label clinical trial, 160 patients hospitalized equally divided between moderate and severe COVID19 categories were randomized to 4 study groups in a 1:1:1:1 allocation (n = 40 for each group) according to type of treatment. Patients were randomly assigned to receive the standard treatment for 14 days (control group) or colchicine add on to the standard treatment 1 mg daily orally for 7 days then 0.5 mg daily for another 7 days. Survival rate, time to cure in days, and side effects were assessed. Results: Colchicine add on treatment was associated with a significantly shorter time to cure (referring to start of first symptom) by an average of 5 days in severe disease and 2 days in moderate disease (log-rank P=<0.001). In addition, the Colchicine add on significantly increased the risk of cure per unit of time by 2.69 times compared to controls after adjusting for disease severity, age, and time since the start of the disease to start of treatment. A severe COVID19 disease, a longer time for starting treatment, and the older age notably reduced the risk of cure (HR = 0.72, p = 0.07; HR = 0.74, p < 0.001; and HR = 0.59, p = 0.015 respectively). Possible side effects reported due to colchicine were 8/40 (20%) of severe COVID19 patients and 3/40 (7.5%) of moderate COVID19, non of which warranted stopping treatment by the data monitoring board. Generally, the side effects were 8/11 (72.73%) gastrointestinal disturbances. No immediate or late allergic reactions were observed. Conclusions: Colchicine add on treatment reduced significantly time to recovery in severe COVID19 (by five days) and in moderate cases (by two days) but did not lower the death rate. Side effects were mild, well tolerated and confined to gastrointestinal adverse events.
ABSTRACT
BACKGROUND: COVID-19 pandemic has ignited the urge for repurposing old drugs as candidate antiviral medicines to treat novel challenges of viral infections. Niclosamide (NCS) is an anti-parasitic drug of known antiviral potential. Therefore, this study attempts to investigate the antiviral effect and safety of NCS on SARS-CoV-2 caused COVID-19 patients. METHODS: Randomized controlled open label clinical trial encompassed 75 COVID-19 patients treated with standard of care plus NCS were included as experimental group and 75 COVID-19 patients treated with only standard of care therapy as control group. Survival rate, time to recovery, and side effects were the main endpoints for the assessment of the therapeutic effect and safety of NCS. RESULTS: No significant difference between the two study groups in the incidence of death Vs recovery within 30 days of follow up(p = 1).Median survival time to cure in the NCS addon group was significantly less than controls (5 Vs 7days, Log rank p = 0.005).All the recoveries took place within 20 days in the NCS add on group, which is 10 days shorter than that in the controls (30 days), NCS add on treatment increased the risk of cure by 60% per day compared to control group (adjusted HR = 1.6,p = 0,007) after adjusting for the count of comorbidities. Additionally, two or more comorbidities reduced the risk of cure to 33% (p < 0.001).Male gender increased the risk of cure by 42% (p = 0.046). Older age group decreased the risk of recovery per day to 0.58 and 0.53 for 50-59 and 60+ years of age. Hyypertension (HT) and diabetes mellitus (DM) significantly reduced the risk of being cured per day to 0.56 (p = 0.003)and 0.65 (p = 0.039) respectively. No significant signals of safety in NCS add on therapy compared to control group. CONCLUSION: adding NCS to the standards of care measures increased the risk of the cure and had shorter time to stay in the hospital compared with controls., male gender increased the risk of cure, while older patients>40 years, HT, and DM decreased the risk of cure. Also, NCS add on therapy was relatively safe; hence, NCS is of clinical benefit for freeing hospital beds for more patients in pandemic crisis.