Table 2c. Ivermectin: Selected Clinical Data

Last Updated: February 11, 2021

The clinical trials described in this table do not represent all the trials that the Panel reviewed while developing the recommendations for IVM. The studies summarized below are those that have had the greatest impact on the Panel’s recommendations.

Table 2c. Ivermectin: Selected Clinical Data
Study Design Methods Results Limitations and Interpretation
Ivermectin Versus Ivermectin Plus Doxycycline Versus Placebo for Treatment of COVID-191
Randomized, double-blind, placebo-controlled trial of hospitalized adults in Dhaka, Bangladesh (n = 72) Key Inclusion Criteria:
  • Aged 18–65 years
  • Laboratory-confirmed SARS-CoV-2 infection with fever, cough, or sore throat
  • Admitted to hospital within previous 7 days

Key Exclusion Criteria:

  • Chronic cardiac, renal, or liver disease

Interventions:

  • IVM 12 mg PO once daily for 5 days
  • Single dose of IVM 12 mg PO plus DOX 200 mg PO on Day 1, then DOX 100 mg every 12 hours for 4 days
  • Placebo

Primary Endpoints:

  • Time to virologic clearance, measured by obtaining an NP swab for SARS-CoV-2 PCR on Days 3, 7, and 14, then weekly until PCR result was negative
  • Resolution of fever and cough within 7 days
Number of Participants:
  • IVM (n = 24; 2 withdrew), IVM plus DOX (n = 24; 1 withdrew), and placebo (n = 24; 1 withdrew)

Participant Characteristics:

  • Mean age was 42 years.
  • 54% of participants were female.
  • Mean time from symptom onset to assessment was 3.83 days.
  • No patients required supplemental oxygen.

Primary Outcomes:

  • Shorter mean time to virologic clearance with IVM than placebo (9.7 days vs. 12.7 days; P = 0.02), but not with IVM plus DOX (11.5 days; P = 0.27).
  • Rates of virologic clearance were greater in IVM arm at Day 7 (HR 4.1; 95% CI, 1.1–14.7; P = 0.03) and at Day 14 (HR 2.7; 95% CI, 1.2–6.0; P = 0.02) compared to placebo, but not in the IVM plus DOX arm (HR 2.3; 95% CI, 0.6–9.0; P = 0.22 and HR 1.7; 95% CI, 0.8–4.0; P = 0.19).
  • No statistically significant difference in time to resolution of fever, cough, or sore throat between IVM and placebo arms (P = 0.35, P = 0.18, and P = 0.35, respectively) or IVM plus DOX and placebo arms (P = 0.09, P = 0.23, and P = 0.09, respectively).

Other Outcomes:

  • Mean values of CRP, LDH, procalcitonin, and ferritin declined in all arms from baseline to Day 7, but there were no between-arm comparisons of the changes.
  • No between-arm differences in duration of hospitalization (P = 0.93).
  • No SAEs recorded.
Limitations:
  • Small sample size
  • Not clear whether both IVM and DOX placebos were used.
  • Patients with chronic diseases were excluded.
  • Disease appears to have been mild in all participants; thus, the reason for hospitalization is unclear.
  • Absolute changes in inflammatory markers are not presented but were reportedly significant.
  • PCR results are not a validated surrogate marker for clinical efficacy.

Interpretation:

  • A 5-day course of IVM resulted in faster virologic clearance than placebo, but not a faster time to resolution of symptoms (fever, cough, and sore throat). Because time to virologic clearance is not a validated surrogate marker for clinical efficacy, the clinical efficacy of IVM is unknown.
Ivermectin Versus Placebo for Outpatients With Mild COVID-192
Open-label RCT of adult outpatients in Lahore, Pakistan (n = 50) Key Inclusion Criteria:
  • SARS-CoV-2 PCR positive
  • Mild disease

Key Exclusion Criteria:

  • Severe symptoms likely related to cytokine storm
  • Malignancy, chronic kidney disease, or cirrhosis
  • Pregnancy

Interventions:

  • IVM 12 mg PO immediately, followed by 12 mg doses at 12 and 24 hours, plus symptomatic treatment
  • Symptomatic treatment

Primary Endpoint:

  • Symptoms reported on Day 7. Patients were stratified as asymptomatic or symptomatic.
Number of Participants:
  • IVM (n = 25) and control (n = 25)

Participant Characteristics:

  • Mean age was 40.6 years.
  • 62% of participants were male.
  • 40% of participants had diabetes, 30% were smokers, 26% had hypertension, 8% had cardiovascular disease, and 12% had obesity.

Outcomes:

  • Proportion of asymptomatic patients at Day 7 was similar in IVM and control arms (64% vs. 60%; P = 0.500).
  • AEs were attributed to IVM in 8 patients (32%).
Limitations:
  • Small sample size
  • Open-label study
  • Authors reported the proportions of participants with certain symptoms and comorbidities but did not provide objective assessment of disease severity. This precludes the ability to compare outcomes between arms.
  • Study classified outcomes at Day 7 as “symptomatic” and “asymptomatic,” but did not account for symptom worsening or improvement.

Interpretation:

  • IVM showed no effect on symptom resolution in patients with mild COVID-19.
Ivermectin Plus Doxycycline Versus Hydroxychloroquine Plus Azithromycin for Asymptomatic Patients and Patients with Mild to Moderate COVID-193

RCT of outpatients with SARS-CoV-2 infection with or without symptoms in Bangladesh (n = 116)

This is a preliminary report that has not yet been peer reviewed.

Key Inclusion Criteria:
  • Laboratory-confirmed SARS-CoV-2 infection by RT-PCR
  • SpO2 ≥95%
  • Normal or near-normal CXR
  • No unstable comorbidities

Interventions

Group A:
  • A single dose of IVM 200 μg/kg plus DOX 100 mg twice daily for 10 days
Group B:
  • HCQ 400 mg on Day 1, then HCQ 200 mg twice daily for 9 days plus AZM 500 mg once daily for 5 days

Primary Endpoints:

  • Time to negative PCR result. Asymptomatic patients were tested starting on Day 5, then every other day until a negative result occurred. Symptomatic patients were tested on their second symptom-free day, then every other day until a negative result occurred.
  • Time to resolution of symptoms
Number of Participants:
  • Group A (n = 60) and Group B (n = 56)

Participant Characteristics:

  • Mean age was 33.9 years.
  • 72% of participants were male.
  • 91 of 116 participants (78.5%) were symptomatic.

Outcomes:

  • In Group A, PCR became negative in 60 of 60 patients (100%). Mean time to negative PCR result was 8.93 days (range 8–13 days).
  • In Group B, PCR became negative in 54 of 56 patients (96.4%). Mean time to negative PCR result was 9.33 days (range 5–15 days).
  • Difference between groups in time from recovery to negative PCR result was not statistically significant (P = 0.2314).
  • In a subgroup analysis of patients who were symptomatic at baseline, the mean durations to negative PCR for Groups A and B were 9.06 days and 9.74 days, respectively (P = 0.0714).
  • In the subgroup analysis, the mean symptom recovery durations for Groups A and B were 5.93 days (range 5–10 days) and 6.99 days (range 4–12 days), respectively (P = 0.071).
  • Patients receiving IVM plus DOX had fewer AEs than those receiving HCQ plus AZM (31.7% vs. 46.4%) in the subgroup analysis.
Limitations:
  • Small sample size
  • Open-label study
  • No SOC alone group
  • Study enrolled young patients without major risk factors for disease progression.
  • None of the comparative outcome measures were statistically significant.

Interpretation:

  • In this small study with a young population, the authors suggested that IVM plus DOX was superior to HCQ plus AZM despite no statistically significant difference in time from recovery to negative PCR result and symptom recovery between patients who received IVM plus DOX and those who received HCQ plus AZM.
Effect of Early Treatment With Ivermectin Versus Placebo on Viral Load, Symptoms, and Humoral Response in Patients With Mild COVID-194
A single-center, randomized, double-blind, placebo-controlled pilot trial in Spain (n = 24) Key Inclusion Criteria:
  • Laboratory-confirmed SARS-CoV-2 infection
  • ≤72 hours of symptoms
  • No risk factors for severe disease or COVID-19 pneumonia

Interventions:

  • Single dose of IVM 400 μg/kg
  • Nonmatching placebo tablet administered by a nurse who did not participate in the patient’s care

Primary Endpoint:

  • Positive SARS-CoV-2 PCR result from an NP swab at Day 7 post-treatment
Number of Participants:
  • IVM (n = 12) and placebo (n = 12)

Participant Characteristics:

  • Mean age was 26 years (range 18–54 years).
  • 50% of participants were male.
  • All participants had symptoms at baseline; 70% had headache, 66% had fever, 58% had malaise, and 25% had cough.
  • Median onset of symptoms was 24 hours in IVM arm and 48 hours in placebo arm.

Outcomes:

  • At Day 7, 12 patients (100%) in both groups had a positive PCR (for gene N), and 11 of 12 who received IVM (92%) and 12 of 12 who received placebo (100%) had a positive PCR (for gene E); P = 1.0 for both comparisons.
  • In a post hoc analysis, the authors reported fewer patient-days of cough and anosmia in the IVM-treated patients, but no differences in the patient-days for fever, general malaise, headache, and nasal congestion.
Limitations:
  • Small sample size
  • PCR is not a validated surrogate marker for clinical efficacy.
  • PCR cycle threshold values were higher for patients who received IVM than those who received placebo at some time points, but these comparisons are not statistically significant.
  • Symptom results were not a prespecified outcome and are of unclear statistical and clinical significance.

Interpretation:

  • Patients who received IVM showed no difference in viral clearance compared to those who received placebo.
  • The small sample size and large number of comparisons make it difficult to assess the clinical efficacy of IVM in this population.
Ivermectin Plus Doxycycline Plus Standard Therapy Versus Standard Therapy Alone in Patients With Mild to Moderate COVID-195

Randomized, unblinded, single-center study of patients with laboratory-confirmed SARS-CoV-2 infection in Baghdad, Iran (n = 140)

This is a preliminary report that has not yet been peer reviewed.

Key Inclusion Criteria:
  • Diagnosis by clinical, radiological, and PCR testing
  • Outpatients had mild or moderate COVID-19, while inpatients had severe and critical COVID-19.

Interventions:

  • IVM 200 μg/kg PO daily for 2 days. If patient required more time to recover, a third dose was given 7 days after the first dose, plus DOX 100 mg twice daily for 5–10 days plus standard therapy (based on clinical condition).
  • Standard therapy was based on clinical condition and included AZM, acetaminophen, vitamin C, zinc, vitamin D3, dexamethasone 6 mg daily or methylprednisolone 40 mg twice daily if needed, and oxygen or mechanical ventilation if needed.
  • All critically ill patients were assigned to receive IVM plus DOX.
Number of Participants:
  • IVM plus DOX plus standard therapy (n = 70) and standard therapy alone (n = 70)

Participant Characteristics:

  • Median age was 50 years in IVM arm and 47 years in standard therapy arm.
  • 50% of patients were male in IVM arm and 53% were male in standard therapy arm.
  • In IVM arm, 48 patients had mild or moderate COVID-19, 11 had severe COVID-19, and 11 had critical COVID-19.
  • In standard therapy arm, 48 patients had mild or moderate COVID-19, 22 had severe COVID-19, and no patients had critical COVID-19.

Outcomes:

  • Mean recovery time in IVM arm was 10.1 days (SD 5.3 days) vs. 17.9 days (SD 6.8 days) for standard therapy arm (P < 0.0001). This result was only significant for those with mild to moderate disease.
  • Disease progression occurred in 3 of 70 patients (4.3%) in IVM arm and 7 of 70 (10.0%) in standard therapy arm (P = 0.19)
  • 2 of 70 patients (2.85%) in IVM arm and 6 of 70 (8.57%) in standard therapy arm died (P = 0.14)
Limitations:
  • Not blinded
  • Patient deaths prevent an accurate comparison of mean recovery time between arms in this study, and the authors did not account for competing mortality risks.
  • Relies heavily on post hoc subgroup comparisons.
  • Substantial imbalance in disease severity at baseline
  • Authors noted that critical patients were not assigned to standard therapy arm; thus, the arms were not truly randomized.
  • Unclear how many patients required corticosteroids.

Interpretation:

  • IVM may shorten the time to recovery for patients with mild or moderate disease, but the lack of control for competing mortality causes in the study limits the ability to interpret the results.
Efficacy and Safety of Ivermectin Versus Hydroxychloroquine for Treatment of COVID-196

Multicenter RCT that compared the use of IVM and HCQ in patients with mild, moderate, or severe COVID-19 in hospital settings (n = 400)

This is a preliminary report that has not yet been peer reviewed.

Key Inclusion Criteria:
  • Positive RT-PCR result
  • Mild, moderate, or severe cases of COVID-19

Key Exclusion Criteria:

  • Contraindications for HCQ
  • Critical cases of COVID-19
  • Chronic kidney, liver, or heart disease

Interventions

All Patients:
  • SOC, which included AZM 500 mg once daily for 6 days, vitamin C 1 gm once daily, zinc 50 mg once daily, lactoferrin 100 mg twice daily, acetylcysteine 200 mg 3 times daily, prophylactic or therapeutic anticoagulation if D-dimer >1,000, and paracetamol as needed.
Group 1 (Mild or Moderate) and Group 3 (Severe):
  • IVM 400 μg/kg once daily for 4 days (maximum of IVM 24 mg per day)
Group 2 (Mild or Moderate) and Group 4 (Severe):
  • HCQ 400 mg every 12 hours on Day 1, then HCQ 200 mg every 12 hours for 5 days
Primary Endpoints:
  • Clinical laboratory improvement and/or 2 consecutive negative PCR results ≥48 hours apart
  • Length of hospital stay
Number of Participants
  • All 4 arms (n = 100 in each arm)

Participant Characteristics:

  • Mean age was 53.8–59.6 years.
  • 67% to 72% of patients were male.
  • Fatigue and dyspnea reported in 36% to 38% of patients with mild or moderate disease and 86% to 88% of those with severe disease.

Primary Outcomes:

  • In those with mild or moderate disease, patients who received IVM had significant differences in improvement compared to those who received HCQ (99% vs. 74%), progression of disease (1% vs. 22%), death (0% vs. 4%), and mean number of hospital days (5±1 vs. 15±8) (P < 0.001 for all parameters except death).
  • For those with severe disease, patients who received IVM had significant differences compared to those who received HCQ in improvement (94% vs. 50%), progression of disease (4% vs. 30%), death (2% vs. 20%), and mean number of hospital days (6±8 vs. 18±8) (P < 0.001 for all parameters).
  • For all patients, those treated with IVM had significant improvement in TLC, CRP, ferritin, D-dimer, and RT-PCR conversion days by Week 1 (P < 0.001) compared to those who received HCQ.
  • In addition to the markers listed above, patients with severe disease showed greater improvement in hemoglobin in IVM arm than in HCQ arm.
Limitations:
  • Unclear whether the study team and patients were blinded.
  • The role of SOC therapy in clinical and laboratory responses is unknown.
  • Cannot rule out potential harm from HCQ. It is unknown whether using AZM plus HCQ could have led to worse outcomes.
  • No SOC alone group
  • Laboratory results are only reported after 1 week of treatment. Length of follow up for clinical outcomes and mortality is unclear.

Interpretation:

  • Compared to those who received HCQ, IVM recipients had improved inflammatory markers and time to RT-PCR conversion after 1 week. Improvement in clinical status and decreased mortality was also observed in the IVM arm
Antiviral Effect of High-Dose Ivermectin in Adults with COVID-197

Multicenter, randomized, open-label, blinded trial of hospitalized adults with mild to moderate COVID-19 (n = 45)

This is a preliminary report that has not yet been peer-reviewed.

Key Inclusion Criteria:
  • Laboratory-confirmed SARS-CoV-2 infection
  • Hospitalized with WHO Stage 3 to 5 COVID-19
  • ≤5 days of symptoms

Key Exclusion Criteria:

  • Use of any agent with potential anti-SARS-CoV-2 activity or immunomodulators prior to enrollment
  • Poorly controlled comorbidities

Interventions:

  • IVM 600 μg/kg once daily plus SOC for 5 days
  • SOC for 5 days
Primary Endpoint:
  • VL reduction at Day 5. VL was quantified by NP swab at baseline, then at 24, 48, and 72 hours and Day 5.
PK Sampling:
  • Performed 4 hours after dose on Days 1, 2, 3, 5, and 7 to assess elimination
Number of Participants
  • IVM (n = 30) and SOC (n = 15)
  • After excluding patients with poor sample quality, those without a detectable VL at baseline, and those who withdrew, 32 patients (20 IVM, 12 SOC) were included in the viral efficacy analysis population.

Participant Characteristics:

  • Mean age was 40.9 years ± 12.5 years.
  • 56% of patients were male.

Primary Outcomes:

  • Nonstatistically significant difference in baseline VL between arms. The baseline median VL was 3.74 log10 copies/mL (range 2.8–5.79) in IVM arm and 5.59 log10 copies/mL in SOC arm (P = 0.08).
  • By Day 5, a similar magnitude of viral reduction was seen in both arms.

Other Outcomes:

  • A significant positive correlation was found after analysis of mean plasma IVM concentration in relation to VL reduction. Participants with higher IVM concentrations had greater reductions in VL (r 0.44; P < 0.04). This correlation was stronger when reduction in VL was related to the IVM exposure corrected by baseline VL (r 0.60; P < 0.004).
  • Treated patients were divided into 2 groups based on IVM Cmax: IVM >160 ng/mL (median of 202 ng/mL) and ≤160 ng/mL (median of 109 ng/mL).
    • Median percentage of VL reduction by Cmax concentration vs. control (P = 0.0096) was 72% (IQR 59% to 77%) in >160 ng/mL group (n = 9), 40% (IQR 21% to 46%) in ≤160 ng/mL group (n = 11), and 42% (IQR 31% to 73%) in SOC arm.
    • Median viral decay rate (P = 0.041) was 0.64 d-1 in >160 ng/mL group, 0.14 d-1 in ≤160 ng/mL group, and 0.13 d-1 in SOC arm.
  • Percentages of AEs were similar between the arms (43% in IVM arm, 33% in SOC arm), and AEs were mostly mild. No correlation was found between IVM concentration and the occurrence of AEs.
Limitations:
  • Small sample size
  • No clinical response data reported.
  • The Cmax level of 160 ng/mL used in the analysis appears to be arbitrary.

Interpretation:

  • Concentration-dependent virologic response was seen using a higher-than-usual dose of IVM (600 μg/kg vs. 200 or 400 μg/kg once daily), with minimal associated toxicities.
  • The study results showed large interpatient variation of IVM Cmax. Larger sample sizes are needed to further assess the safety and efficacy of using higher doses of IVM to treat COVID-19.
Ivermectin as Adjunctive Therapy to Hospitalized Patients With COVID-198

Randomized, double-blind, placebo-controlled multicenter Phase 2 clinical trial of hospitalized adults with mild to severe SARS-CoV-2 infection in 5 facilities in Iran (n = 180)

This is a preliminary report that has not yet been peer-reviewed.

Key Inclusion Criteria:
  • Symptoms suggestive of COVID-19 pneumonia, with chest CT compatible with mild to severe COVID-19 or positive RT-PCR result for SARS-CoV-2

Key Exclusion Criteria:

  • Severe immunosuppression, malignancy, or chronic kidney disease
  • Pregnancy

Interventions:

  • HCQ 200 mg/kg twice daily alone as SOC (standard arm)
  • SOC plus 1 of the following:
    • Placebo
    • Single dose of IVM 200 μg/kg
    • IVM 200 μg/kg on Days 1, 3, and 5
    • Single dose of IVM 400 μg/kg
    • IVM 400 μg/kg on Day 1, then IVM 200 μg/kg on Days 3 and 5
Primary Endpoint:
  • Clinical recovery within 45 days of enrollment (defined as normal temp, respiratory rate, and SpO2 >94% for 24 hours)
Number of Participants
  • All 6 arms (n = 30 in each arm)

Participant Characteristics:

  • Average age was 56 years (range 45–67 years).
  • 50% of patients were male.
  • Disease stratification (based on CT findings): negative (1%), mild (14%), moderate (73%), and severe (12%)
  • Mean SpO2 at baseline was 89%.

Primary Outcomes:

  • Durations of hypoxemia (P = 0.025) and hospitalization (P = 0.006) were shorter in the IVM arms compared to placebo arm, and mortality was lower in the IVM arms (P = 0.001).
  • There was no difference in number of days of tachypnea (P = 0.584) or return to normal temperature (P = 0.102).
  • Significant differences in change from baseline to Day 5 in absolute lymphocyte count, platelet count, erythrocyte sedimentation rate, and CRP.
  • Higher mortality was reported in standard and placebo arm than IVM arms.
Limitations:
  • Small study
  • Power estimation is confusing.
  • Mortality was not listed as the primary or secondary outcome.
  • It is unclear whether IVM patients also received HCQ.
  • It is unclear whether the between-group comparisons are between combined IVM group and placebo plus SOC.
  • Participants were stratified by disease severity based on CT findings. These categorizations are unclear and were not taken into account in outcome comparisons.
  • The post hoc grouping of randomized arms raises risk of false positive findings.

Interpretation:

  • IVM appeared to improve laboratory outcomes and some clinical outcomes (shorter duration of hypoxemia and hospitalization) and lowered mortality.
  • The small size of the study, the unclear treatment arm assignments, and the lack of accounting of disease severity at baseline make it difficult to draw conclusions about the efficacy of using IVM to treat patients with mild COVID-19.
Retrospective Analysis of Ivermectin in Hospitalized Patients With COVID-199
Retrospective analysis of consecutive patients with laboratory-confirmed SARS-CoV-2 infection who were admitted to 4 Florida hospitals (n = 276) Key Inclusion Criteria:
  • Positive NP swab with SARS-CoV-2 RNA

Interventions:

  • Single dose of IVM 200 µg/kg, repeated on Day 7 at the doctors’ discretion; 90% percent of patients also received HCQ.
  • Usual care: 97% of patients received HCQ and most also received AZM.
Primary Endpoint:
  • All-cause, in-hospital mortality
Number of Participants:
  • IVM (n = 173; 160 participants received a single dose, 13 participants received a second dose) and usual care (n = 103)

Participant Characteristics:

  • Mean age was 60.2 years in IVM arm and 58.6 years in the usual care arm.
  • 51.4% of patients were male in IVM arm and 58.8% were male in usual care arm.
  • 56.6% of patients were Black in IVM arm and 51.4% were Black in usual care arm.

Outcomes:

  • All-cause mortality was lower in IVM arm than in usual care arm (OR 0.27; 95% CI, 0.09–0.80; P = 0.03); the benefit appeared to be limited to the subgroup of patients with severe disease.
  • No difference in median length of hospital stay between arms (7 days for both) or proportion of mechanically ventilated patients who were successfully extubated (36% in IVM arm vs. 15% in usual care arm; P = 0.07).
Limitations:
  • Not randomized
  • Little to no information on oxygen saturation or radiographic findings
  • Timing of therapeutic interventions was not standardized.
  • Ventilation and hospitalization duration analyses do not appear to account for death as a competing risk.
  • No virologic assessments were performed.

Interpretation:

  • IVM use was associated with lower mortality than usual care. However, the limitations of this retrospective analysis make it difficult to draw conclusions about the efficacy of using IVM to treat patients with COVID-19.
Observational Study on the Effectiveness of Hydroxychloroquine, Azithromycin, and Ivermectin Among Hospitalized Patients With COVID-1910

Retrospective cohort study of hospitalized adults with COVID-19 in Peru (n = 5,683)

This is a preliminary report that has not yet been peer-reviewed.

Key Inclusion Criteria:
  • Aged ≥18 years
  • Symptomatic
  • Laboratory-confirmed SARS-CoV-2 infection
  • No life-threatening illness at admission

Key Exclusion Criteria:

  • Required oxygen at admission
  • Use of tocilizumab, LPV/RTV, or RDV

Interventions:

  • One of the following interventions administered within 48 hours of admission:
    • HCQ or CQ alone
    • IVM alone
    • AZM alone
    • HCQ or CQ plus AZM
    • IVM plus AZM
    • SOC (e.g., supportive care, antipyretics, hydration)

Primary Endpoint:

  • All-cause mortality

Secondary Endpoint:

  • All-cause mortality and/or transfer to ICU
Number of Participants:
  • HCQ or CQ alone (n = 200), IVM alone (n = 203), AZM alone (n = 1,600), HCQ or CQ plus AZM (n = 692), IVM plus AZM (n = 358), and SOC (n = 2,630)

Participant Characteristics:

  • 63% of patients were male.
  • Mean age was 59.4 years (range 18–104 years).
  • All patients had mild or moderate disease.

Outcomes:

  • Median follow-up time was 7 days. Mortality rate was 18.9% at the end of follow up.
  • IVM alone was associated with increased risk of death and/or ICU transfer compared to SOC (wHR 1.58; 95% CI, 1.11–2.25).
  • IVM plus AZM did not have an effect on deaths or any secondary outcomes (all-cause death and/or ICU transfer, all-cause death and/or oxygen prescription) compared to SOC.
  • HCQ or CQ plus AZM was associated with a higher risk of death (wHR 1.84; 95% CI, 1.12–3.02), death and/or ICU transfer (wHR 1.49; 95% CI, 1.01–2.19), and death and/or oxygen prescription (wHR 1.70; 95% CI, 1.07–2.69) compared to SOC.
Limitations:
  • Not randomized
  • Unclear whether all patients received IVM or other medications according to Peruvian guidelines referred to in the manuscript.
  • Dosing and timing of administration are unclear.

Interpretation:

  • Compared to SOC, IVM alone was associated with increased risk of death and/or ICU admission. Using IVM in combination with AZM was not associated with effects on mortality, ICU transfer, or oxygen prescription compared to SOC.
Retrospective Study of Ivermectin Versus Standard of Care in Patients With COVID-1911

Retrospective study of consecutive adult patients hospitalized in Bangladesh with laboratory-confirmed SARS-CoV-2 infection (n = 248)

Key Inclusion Criteria:
  • Aged ≥18 years
  • Positive NP swab with SARS-CoV-2 RNA
  • “Free from any other serious pathological conditions”

Interventions:

  • Single dose of IVM 12 mg within 24 hours of hospital admission
  • SOC

Primary Endpoint:

  • Not specified
Number of Participants
  • IVM (n = 115) and SOC (n = 133)

Participant Characteristics:

  • Median age in IVM arm was 34 years; 70% of participants were male.
  • Median age in SOC arm was 35 years; 52% of participants were male.
  • All participants had mild or moderate disease.
  • 12% of participants had hypertension in both arms.
  • 17% of participants in IVM arm and 12% in SOC arm had diabetes mellitus.

Outcomes:

  • Fewer patients in IVM arm had evidence of disease progression compared to SOC arm (P < 0.001): moderate respiratory distress (2.6% vs. 15.8%), pneumonia (0% vs. 9.8%), ischemic stroke (0% vs. 1.5%).
  • Fewer patients in IVM arm required intensive care management compared to SOC arm (0.9% vs. 8.8%; P < 0.001).
  • Fewer patients in IVM arm required antibiotic therapy (15.7% vs. 60.2%; P < 0.001) or supplemental oxygen (9.6% vs. 45.9%; P < 0.001) compared to SOC arm.
  • Shorter median duration of viral clearance in IVM arm compared to SOC arm (4 vs. 15 days; P < 0.001).
  • Shorter median duration of hospital stay in IVM arm compared to SOC arm (9 vs. 15 days; P < 0.001)
  • Lower mortality in IVM arm compared to SOC arm (0.9% vs. 6.8%; P < 0.05)
Limitations:
  • Not randomized
  • Disease severity at admission was reported as mild or moderate, but 12% of patients in IVM arm and 9% in SOC arm had SpO2 <94%
  • Even though only 10% of patients developed pneumonia, 60% received antibiotics.
  • Possibility of harm from concomitant medications

Interpretation:

  • Compared to SOC, IVM use was associated with faster rates of viral clearance and better clinical outcomes, including shorter hospital stay and lower mortality.