Summary of findings 2. Summary of findings table 2.
| Ivermectin for treating COVID‐19 in outpatient settings with asymptomatic or mild disease | ||||||
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Patient or population: all trials contributing results to the summary of findings table included people with mild disease (WHO scale 1 to 3)§ Setting: outpatients Intervention: ivermectin plus standard of care Comparison: standard of care plus/minus placebo | ||||||
| Outcomes | Anticipated absolute effects* (95% CI) | Relative effect (95% CI) | № of participants (trials) | Certainty of the evidence (GRADE) | Comments | |
| Risk with standard of care plus/minus placebo | Risk with ivermectin | |||||
| All‐cause mortality at day 28 | 27 per 1000 | 21 per 1000 (13 to 34) | RR 0.77 (0.47 to 1.25) | 2860 (6 RCTs) | ⨁⨁⨁◯ Moderatea |
Ivermectin probably has little or no effect on all‐cause mortality at day 28. |
| Worsening of clinical status: admission to hospital or death within 28 days | 74 per 1000 | 81 per 1000 (15 to 445) | RR 1.09 (0.20 to 6.02) | 590 (2 RCTs) | ⨁⨁◯◯ Lowb |
Ivermectin may have little or no effect on clinical admission to hospital or death within 28 days. |
| Improvement of clinical status: all initial symptoms resolved (asymptomatic) at day 14 | 591 per 1000 | 532 per 1000 (355 to 804) | RR 0.90 (0.60 to 1.36) | 478 (2 RCTs) | ⨁⨁◯◯ Lowc |
Ivermectin may have little or no effect on clinical improvement, assessed by the number of participants with all initial symptoms resolved up to 14 days. |
| Improvement of clinical status: time to symptom resolution | NA | NA | NA | NA | NAd | No trial reported data for time to symptom resolution suitable for meta‐analysis. |
| QoL (physical component) at up to 28 days, measured on the PROMIS Global‐10 scale and normalized to values from 16.2, low QoL, to 67.2, maximum QoL | The mean score on a numerical quality of life scale was 49.6 points with a SD of 10.4 points | The mean score on a numerical quality of life scale was 49.6 points with a SD of 7.8 points | MD 0.00 (‐0.98 to 0.98) points | 1358 (1 RCT) |
⨁⨁⨁⨁ High |
Ivermectin has little or no effect on QoL (PROMIS Global‐10 physical component) at up to 28 days. |
| QoL (mental component) at up to 28 days, measured on the PROMIS Global‐10 scale and normalized to values from 21.2, low QoL, to 67.6, maximum QoL | The mean score on a numerical quality of life scale was 52.5 points with a SD of 9 points | The mean score on a numerical quality of life scale was 52.5 points with a SD of 11.2 points | MD 0.00 (‐1.08 to 1.08) points | 1358 (1 RCT) | ⨁⨁⨁⨁ High |
Ivermectin has little or no effect on QoL (PROMIS Global‐10 mental component) at up to 28 days. |
| Serious adverse events during the trial period | 4 per 1000 | 9 per 1000 (2 to 33) | RR 2.27 (0.62 to 8.31) | 1502 (5 RCTs) | ⨁⨁◯◯ Lowe |
Ivermectin may have little or no effect on serious adverse events during the trial period. |
| Any adverse events during the trial period | 320 per 1000 | 397 per 1000 (278 to 563) | RR 1.24 (0.87 to 1.76) | 1502 (5 RCTs) | ⨁⨁◯◯ Lowf |
Ivermectin may have little or no effect on any adverse events during the trial period. |
| Viral clearance at day 7 | 237 per 1000 | 240 per 1000 (164 to 351) | RR 1.01 (0.69 to 1.48) | 331 (2 RCTs) | ⨁⨁◯◯ Lowg |
Ivermectin may have little or no effect on viral clearance at day 7. |
| *The risk in the intervention group (and its 95% CI) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: confidence interval; MD: mean difference; NA: not available; RCT: randomized controlled trial; RR: risk ratio; SD: standard deviation; QoL: quality of life; §One contributing trial included people at WHO scale 2 to 4, but was considered an outpatient trial (WHO 2 to 3) based on the trial author's statement (majority of participants were ambulatory and well during admission, hospitalization mostly for isolation and close monitoring only in case of high risk of disease progression based on public health policy at the time of trial). | ||||||
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GRADE Working Group grades of evidence High certainty: we are very confident that the true effect lies close to that of the estimate of the effect. Moderate certainty: we are moderately confident in the effect estimate; the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different. Low certainty: our confidence in the effect estimate is limited; the true effect may be substantially different from the estimate of the effect. Very low certainty: we have very little confidence in the effect estimate; the true effect is likely to be substantially different from the estimate of effect. | ||||||
Explanations aDowngraded one level for serious imprecision due to wide CI. bDowngraded one level for serious inconsistency (I2 = 44%) and one level for serious imprecision due to few events and wide CI. cDowngraded one level for serious risk of bias and one level for serious inconsistency (I2 = 57%). dTwo trials reported the median duration of symptom resolution for ivermectin versus placebo: one study reported 12 days (interquartile range (IQR) 9 to 13 days) in the placebo group versus 10 days (IQR 9 to 13 days) in the ivermectin group, the second study reported 14 days (IQR 11 to 14 days) for both groups. eDowngraded one level for serious risk of bias and one level for serious imprecision due to very few events and wide CI. fDowngraded one level for serious risk of bias (exclusion of one unblinded study with high risk of bias revealed an effect estimate of RR 1.07 (0.84 to 1.36), indicating no difference between ivermectin and placebo) and one level for serious inconsistency (I2 = 80%). gDowngraded one level for serious risk of bias and one level for serious imprecision due to wide CI.