gain, on the surface this looks promising, however going through the individual trials is essential, as the conclusions of any meta-analysis are only as good as the individual trials that go into it. Many of these individual trials have methodological flaws that limit the utility of this analysis.
Poorly Done Trial + Poorly Done Trial + Poorly Done Trial = Poor Conclusion
Discussion:
All of these trials discuss the efficacy of Ivermectin in the treatment of COVID-19 at various time points in illness, but very little was mentioned about safety
Due to its massive global use in low- and middle-income countries, the knowledge base establishing a high margin of safety and low rate of adverse effects is nearly unparalleled
Most common adverse events are mild and transient
Adverse effects are likely attributed to bodies inflammatory response and include itching, rash, swollen lymph nodes, joint pain, fever, and headache
In one trial of 17,877 patients treated with ivermectin 150mcg/kg for Loa loa in Cameroon. Only 20 patients (0.11%) developed serious reactions without neurological signs lasting for more than a week
The definition of insanity: Doing the same thing over and over again and expecting different results
We have seen the adoption of therapeutics too early during this pandemic with many of them not panning out with subsequent RCTs
Hydroxychloroquine is a perfect example of this:
In vitro studies showing decrease in viral load
REBEL EM: COVID-19: Clinical/Therapeutic Staging Proposal and Treatment
Subsequent observational trials showing associations of benefit
REBEL EM: COVID-19 Treatment Update: Can We Just Stop Wasting Time on Hydroxychloroquine
Later randomized clinical trials showing no benefit and potential harms
REBEL EM: Hydroxychloroquine is Ineffective for Post-Exposure Prophylaxis
If you believe the evidence thus far, which are severely flawed: Dosing of Ivermectin Used in Trials
Prophylaxis: 0.2 mg/kg on day 1 and day 3 followed by one dose/month
Treatment 0.2mg/kg o day 1 and day 3 followed by Days 6 and 8 if not recovered
Suggested Dosing of Ivermectin Based on Weight [1]
ADDENDUM (12/21/2020):
I want to be clear about what I am saying in this post. I am not against using ivermectin but not sold on it based on the available data thus far…lots of issues that bias the results to favor ivermectin. Maybe it works or maybe it doesn’t, but I think the jury is still out at this point in time.
ADDENDUM (01/21/2021) – Two More Trials Sent My Way for Review Evidence from Spain [8] What They Did:
Pilot, randomized, double-blind, single-center, parallel-arm, superiority placebo-controlled trial performed in Spain
Evaluating single dose of ivermectin to reduce transmission of SARS-CoV-2 when administered early after disease onset
Consecutive patients with non-severe COVID-19 and no risk factors for complicated disease presenting to the ED
All enrollments occurred within 72hrs of onset of fever or cough
Patients randomized 1:1 to receive:
Ivermectin 400mcg/kg single dose
Placebo single dose
Outcomes:
Primary: Proportion of patients with detectable SARS-CoV-2 RNA by PCR from nasopharyngeal swab at day 7 post treatment
Secondary:
Viral load at days 4, 7, 14, and 21 post treatment
Proportion of patients with symptoms (fever and cough) at days 4, 7, 14, and 21 post treatment
Proportion of patients progressing to severe disease or death during the trial
Proportion of patients with seroconversion at day 21 post treatment
Proportion of drug-related adverse events
Inclusion:
Patients presenting to the ED
Symptoms compatible with COVID-19
No more than 72hrs of fever or cough
Positive PCR for SARS-CoV-2
Exclusion:
Positive IgG against SARS-CoV-2
Comorbidities considered risk factors for severe disease
COVID-19 pneumonia at baseline
Results:
24 total patients
100% had symptoms at recruitment
Proportion of patients with Detectable SARS-CoV-2 at Day 7 Post Treatment:
Ivermectin:
Gene N: 100%
Gene E: 91%
Placebo:
Gene N: 100%
Gene E: 100%
RR 0.92; 95% CI 0.77 – 1.09; p = 1.0
Ivermectin group had significantly lower viral loads at day 4 (3-fold lower) and day 7 (18-fold lower)
Confidence intervals crossed at all time points making this not statistically significant
Symptoms
Fewer days of any symptoms, however driven by anosmia/hyposmia (50% less) and cough (30% less)
No patients from either group progressed to severe disease
IgG Titers:
All patients in both groups seroconverted by day 21 post treatment
Lower IgG titers at day 21 post treatment in the ivermectin group (4.7 vs 7.5)
Not statistically significant
Safety:
No severe adverse events in either group
More dizziness and blurred vision with Ivermectin
Strengths:
Asks a clinically relevant question
Randomized, double-blind, placebo-controlled trial
All patients recruited completed the trial
No difference in vital signs, inflammatory markers or blood counts between groups
Limitations:
Small trial (n = 24 patients)
Surrogate soft outcomes without any patient oriented outcomes (i.e. mortality)
Placebo tablets did not match Ivermectin tablets which could lead to unblinding
Slow recruitment (24 patients over 10 weeks)
94 patients assessed however many excluded due to not wanting to participate, or asymptomatic (70 patients excluded)
Trial too small to make any conclusions about adverse effects
Only included healthy patients with no comorbid disease
Discussion:
Authors were looking for a 50% reduction in the proportion of positive SARS-CoV-2. This large reduction was due to the small size of the trial.
Endpoint of negative PCR is not reflective of disease as patient can be fully recovered but still have enough viral material to be amplified by PCR (ie irrelevant viral material)
credited to rebelem
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