Replies

Baseline demographic and clinical characteristics

Between 1 September 2021 and 30 November 2021, 208 patients with mild-to-moderate COVID-19 infection within 3 days of symptoms onset were assessed for eligibility. Of the 208 assessed individuals, 134 were excluded due to severe co-morbid diseases, such as asthma and active malignancies, age-related ineligibility, and unwillingness to participate.

One patient each from the ivermectin and placebo group withdrew their consent during the study due to drug addiction and psychiatric problems.

The remaining 72 patients were equally randomized to either the ivermectin plus standard care (n=36) group or the placebo plus standard care (n=36) group (Figure 1). The mean age of all the enrolled cases was 48.57± 14.80 years, patients in both groups were balanced in demographic and disease characteristics at baseline (Table 1).

The mean age of cases in the control and intervention arms were not significantly different (47.72± 15.45 years versus 49.42± 29 years, p=0.631). The majority of patients in both the control and intervention group were female (63.9% and 61.1%, respectively). The main concomitant diseases were hypertension (49%), dyslipidemia (34.7 %), and diabetes mellitus (23.6 %). The biochemical parameters were not significantly different between both the groups and were all within normal limits (Supplemental File)

Clinical Outcomes

The most common symptoms were fever (43.1%), cough (77.8%), runny nose (50%), followed by loss of smell and taste (30.6 and 23.6%, respectively), sore throat (37.5%), and diarrhea (11%) (Table 2). The proportion of patients in the ivermectin group recovered from various symptoms sooner than those in the control group, such as cough (OR: 0.54; 95% CI: 0.15–1.94; p=0.346), smell disturbance (OR: 0.34; 95% CI: 0.04–3.11; p=0.342), runny nose (OR: 0.37, 95% CI: 0.08–1.67; p=0.196), fatique (OR: 0.13; 95% CI: 0.00–8.94; p=0.345), and headache (OR: 0.24; 95% CI: 0.03–1.71; p=0.153), although the difference was not statistically significant.

Table 3 shows the baseline and follow-up hemodynamics and vital signs from day 1 to day 14. Both the control and treatment arms demonstrated stable blood pressure control, oxygen saturation, and respiratory rate throughout the disease course. None of the patients required intensive care (ICU) admission or invasive ventilation. Nearly all of the patients were discharged by day 14, except two patients that requested to get discharged on day 10, and returned to repeat their laboratory tests on day 14 on an outpatient basis. The hemodynamic characteristics were not significantly different between the two groups from baseline until day 14. Time till resolution of symptoms in patients assigned to the ivermectin versus placebo group was not significantly different between both the groups (HR: 1.18; 95% CI: 0.67–2.08; p=0.572) (Figure 2).

Primary Outcome

The proportion of patients in the treatment and control arm whose reverse transcription polymerase chain reaction (RT-PCR) result was negative on day 7 (7 [17.3%] vs 6 [14.3%], respectively; p=0.743) and day 14 (17 [47.2%] vs 16 [44.4%], respectively; p=0.813) of enrollment was not significant different (Table 4).

Furthermore, the Ct ratio on day 14 was also not significantly different between the treatment and control groups (17.43 ± 16.82 vs 18.51 ± 17.34, respectively; p=0.788). One-third of the patients in each group still had residual abnormal chest radiograph at day 14 (12 [33%] vs 11 [30.6%] in the treatment and control group; p= 0.800).

Secondary Outcome

All patients survived at day 28 and almost all of them (,92.1%) were admitted in the hospital until day 14. The proportion of patients who felt healthy on day 14 were not significantly different between the two treatment groups. The remaining symptoms upon discharge in the treatment and control arms were cough (19.4% and 19.4%), dyspnea (5.6% and 0%), smell disturbance (0% and 8.3%), runny nose (0.28% and 0%), sore throat (5.6% and 0%), headache (0% and 5.6%), muscle pain (8.3% and 2.8%), and malaise (0% and 5.6%). None of the patients required escalation of care. There were no major differences in the evolution of vital signs (Table 3), inflammatory markers (C-reactive protein, procalcitonin, ferritin, and interleukin-6), and other laboratory parameters in patients belonging to each group (Supplemental File).

However, the time to resolution of many symptoms, such as cough (HR: 1.19 [95% CI: 0.71–1.99]; p=0.513), runny nose (HR: 1.36 [95%CI: 0.84–2.21]; p=0.206), smell disturbances (HR: 1.23 [95% CI: 0.76–199]; p=0.391), and fatique (HR: 1.19 [95%CI: 0.73–1.92], p=0.488) were reported to be shorter, eventhough the difference was not statistically significant.

Effect of vaccination

The proportion of patients who received vaccination was not differed between the two groups, regardless of receiving one or two doses of a vaccine. Most patients were vaccinated with the ChAdOx1 nCoV-19 (Oxford-AstraZeneca) vaccine.

Of the vaccinated patients, 47.2% received their first dose while only 18% received both doses of the vaccine (p=0.636). Time from last dose of vaccination to COVID-19 infection was comparable in both the ivermectin and control group.

Adverse events

All patients completed the follow-up period of 28 days. No adverse events were recorded in any patients during the trial period (14 days) and up to 28 days of follow up.

There were no major differences in the evolution of vital signs, inflammatory markers (C-reactive protein, procalcitonin, and interleukin-6), and other laboratory parameters of patients in both the groups (Supplemental File).