The Efficacy and safety of Ivermectin in the treatment of mild-to-moderate COVID-19 infection: A randomized, double blind, placebo, controlled trial

Research Square ^ | 02/02/2002 | Anan Manomaipiboon, Kitisak Pholtawornkulchai, Sujaree Pupipatpab, et. al.,

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Abstract

The emergent outbreak of coronavirus disease (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has emphasized the requirement for therapeutic opportunities to overcome this pandemic.

Ivermectin is an antiparasitic drug that has shown to be effective against various agents, including SARS-CoV-2, and is under extensive research in clinical trials.

In this randomized, double-blind, placebo-controlled trial among adult hospitalized patients with mild-to-moderate COVID-19, 72 patients (mean age 48.57 ± 14.80 years) were randomly assigned to either the ivermectin (n=36) or placebo (n=36) group, along with receiving standard care. The primary outcomes were a negative reverse transcription polymerase chain reaction (RT-PCR) result at day 7 and 14 of enrolment.

The secondary outcomes were duration of hospitalization, frequency of clinical worsening, survival on day 28, and adverse events. At day 7 and 14, a negative RT-PCR result was not significantly different between the two groups.

The other secondary outcomes were reported to be comparable. However, the time to resolution of many symptoms were shorter in the Ivermectin group, albeit not significantly.

No adverse events were reported. In conclusion, early symptomatic recovery was observed with no side effects after treatment with Ivermectin and standard care in mild-to-moderate COVID-19 patients.

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Ping for your interest

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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).

[rightwingcrazy]

I can find no mention of dosage.

[SeekAndFind]

You'll have to read the article in detail. But it says under the section STUDY DESIGN

This study was a randomized, double-blind, placebo controlled trial, conducted at the Faculty of Medicine, Vajira Hospital, Navamindradhiraj University, from September 2021 to November 2021.

The patients were randomized in a permuted block of four in a randomized sequence prepared by a pharmacist, who was unblinded, in Microsoft excel [28]. Allocation assignment was concealed from the investigators and patients. The patients were allocated in one of the two groups: group A (Ivermectin arm) or group B (control arm), as shown in Figure 1. The patients were randomized in a 1:1 ratio. Group A received 12 mg per day of ivermectin for 5 days, as recommended by previous studies [23, 25], along with standard care. Group B received standard care alone, which included favipiravir or andrographolide, corticosteroids, cetrizine and paracetamol.

[metmom]

Any mention of zinc with it?

Or is it another designed to fail study?

[rightwingcrazy]

Thanks. I’ve seen weight-adjusted dosages recommended elsewhere, but this doesn’t seem to be far off.

[ManardG]

Bookmark for later

[Libloather]

...Manomaipiboon, Pholtawornkulchai, Pupipatpab...

My guess - there's at least one missing vowel in there somewhere.

[SeekAndFind]

From the names, my guess is the research was done by a team in Thailand.

[SeekAndFind]

RE: Any mention of zinc with it?

I tried to look for the word Zinc in the study but it was never mentioned.

RE: Or is it another designed to fail study?

From this study, it looks like it succeeded in showing the efficacy and safety of Ivermectin.

[gas_dr]

Thank you for your post and ping. There are two other things in this study worth noting

1. Exclusions based on severe comorbidities such as asthma were used -- so there is a flaw in the study that it is not examining those whom are at the greatest risk of disease

2. In the present study, a 5 day course of ivermectin did not improve clinical and microbiological outcomes of patients with mild or moderate COVID-19 infection.

The secondary outcome of shortened symptoms is not statistically significant.

Overall this supports Ivermectin as a class 2B intervention -- if not lower. It does not demonstrate any superiority in clinical and microbiological outcomes and excludes those whom are at highest risks. At best, an equivocal study.

[dadfly]

something seems wrong with this study. assuming i read it right, if these are normal male adults, 12 mg dose per day seems way to low to be meaningful. the dose per day has to be adjusted by weight. it can’t be fixed first of all.

12 mg per day. that’s about good for maybe a 50 pound kid. and of course you’ve got to have zinc to get the best use of the ionophoric effects of the drug.

[olivia3boys]

Scott adams pointed this out: if Fauci funded the wuhan lab gain of function research, and the virus escaped from that lab, then really the United States—not China really—caused the Covid pandemic. Fauci is a bureaucrat. He works for the federal government. His actions mean the United States is responsible for the worldwide pandemic. The “blame” on Fauci is a diversion. As a federal employee myself, I see the truth in this.

[Dead Dog]

72 total, averaging in their 40s, too a small sample to see severe disease in the control.

[Cobra64]

FYI… FLCCC dosage recommendations here:

https://covid19criticalcare.com/wp-content/uploads/2020/11/FLCCC-Alliance-I-MASKplus-Protocol-ENGLISH.pdf

[metmom]

IOW, another “study” designed to fail.

Except that it still showed some promise.
Ivermectin must be way better than we thought then.

[FreedomForce]

I’m not sure if ivermectin is a zinc ionophore. I haven’t seen any studies showing that it is. Seen a few assertions from people but haven’t found any papers.

[PsechsySr]

IVM without Zinc, Fluvoxamine, Doxycycline/Z-Pac and a cortical steroid inhaler will have almost no effect. Per Glenn Beck’s doctors, IVM is NOT the silver bullet to take out SARS-CoV-2...Zinc is the silver bullet and IVM helps it to cross the cell barrier, where it interferes with the replication of the virus.