Efficacy and safety of oral ivermectin in the treatment of mild to moderate Covid-19 patients: a multi-centre double-blind randomized controlled clinical trial.

BACKGROUND: Evidence on ivermectin as a treatment for Covid-19 is controversial. A Cochrane review concluded that the efficacy and safety of ivermectin is uncertain (evidence up to April 2022) and WHO recommended its use only in the setting of clinical trials. This study aimed to assess the efficacy and safety of oral ivermectin in hospitalized patients with mild to moderate Covid-19. TRIAL DESIGN AND METHODS: A double-blind, randomized placebo-controlled clinical trial was conducted among RT-PCR-confirmed, adults, hospitalised within the first four days of symptoms. Patients received oral ivermectin 24 mg or placebo daily for five days. RT-PCR was repeated on days five and ten. Clinical progression was monitored using the World Health Organization Clinical Progression Scale. Serum ivermectin levels were measured on days three, five, and seven. The primary outcome was the difference in the viral load between day zero and ten in the two groups. RESULTS: Out of 1699 patients screened, 249 underwent randomization and 127 received ivermectin, and 122 placebo. D10 median viral load for E gene (IQR) was 2,000 copies/mL (100 - 20,500) with ivermectin (n = 80) and 4,100 copies/mL (1,000-65,600) with placebo (n = 81, p = 0.028), per protocol analysis. The difference in Log viral load between day zero and ten between ivermectin and placebo was 3.72 and 2.97 respectively (p = 0.022). There was no significant difference in the WHO clinical progression scale or the adverse effects. Ivermectin blood levels taken before or with meals were not significantly different. Only 7 and 17 patients achieved blood levels above 160ng/ML and 100ng/ML respectively and they did not achieve a significantly lower viral load. CONCLUSION: Although ivermectin resulted in statistically significant lower viral load in patients with mild to moderate Covid-19, it had no significant effect on clinical symptoms. TRIAL REGISTRATION NUMBER: SLCTR/2021/020, Sri Lanka Clinical Trials Registry. 19/07/2021.

Sri Lanka's early success in the containment of COVID-19 through its rapid response: Clinical & epidemiological evidence from the initial case series.

BACKGROUND: Despite the rising global burden, Sri Lanka reported a relatively low caseload and mortality (13 deaths as of 20 October 2020) for COVID-19. This warrants exploration of the clinical and epidemiological characteristics of the case series during the initial passive case detection phase in Sri Lanka, in order to understand the success in containment of the disease for more than nine months in the country through its initial early and rapid pandemic response. METHODS: A retrospective study was conducted using secondary data (hospital records and investigation reports) extracted from all laboratory-confirmed patients admitted to the three main state-sector hospitals in Sri Lanka from 11 March to 7 April 2020. Clinical outcomes were categorized as mild, severe and critical, as per the international classification. Kruskal-Wallis H, Mann Whitney U and Fisher's exact tests compared differences between the variables. RESULTS: The case series comprised 146 live discharges and six deaths. Majority were males (63.2%); mean age of 40.9 (SD = 17.9); and symptomatic (72.4%). Sixty-one (40.1%) had co-morbidities, the commonest being diabetes (20.4%) and hypertension (17.8%). Mild (93.4%), severe (2.6%) and critical (4.0%) disease outcomes were noted. Disease severity was significantly higher with older age (p = 0.037), co-morbidities (p = 0.026); and higher white-cell (p = 0.045) and lymphocyte (p = 0.043) counts; but not with being symptomatic (p = 0.683). The commonest symptoms were fever (62.5%), dry cough (48.0%) and sore throat (26.9%). The median duration (IQR) was 3.0 (1.0-5.0) and 18.0 (15.0-29.5) days, respectively before and during hospitalization. CONCLUSIONS: In contrast to high-risk countries, the younger age, milder disease and low mortality observed in local patients during the initial phase of the pandemic, reflect the early success in containment of the pandemic in Sri Lanka. However, once the disease becomes severe, the factors determining disease fatality remain the same as in other countries. This highlights the value of establishing strong public health systems and disease surveillance in a country, which could provide long-term effects on disease control.