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Ivermectin for COVID-19: real-time meta analysis of 55 studies
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100% of 36 early treatment and prophylaxis studies report positive effects (96% of all 55 studies). 26 studies show statistically significant improvements in isolation.
Random effects meta-analysis with pooled effects using the most serious outcome reported shows 79% and 85% improvement for early treatment and prophylaxis (RR 0.21 [0.11-0.37] and 0.15 [0.09-0.25]). Results are similar after exclusion based sensitivity analysis: 81% and 87% (RR 0.19 [0.14-0.26] and 0.13 [0.07-0.25]), and after restriction to 29 peer-reviewed studies: 82% and 88% (RR 0.18 [0.11-0.31] and 0.12 [0.05-0.30]).
81% and 96% lower mortality is observed for early treatment and prophylaxis (RR 0.19 [0.07-0.54] and 0.04 [0.00-0.58]). Statistically significant improvements are seen for mortality, ventilation, hospitalization, cases, and viral clearance.
100% of the 17 Randomized Controlled Trials (RCTs) for early treatment and prophylaxis report positive effects, with an estimated improvement of 73% and 83% respectively (RR 0.27 [0.18-0.41] and 0.17 [0.05-0.61]), and 93% of all 28 RCTs.
The probability that an ineffective treatment generated results as positive as the 55 studies to date is estimated to be 1 in 23 trillion (p = 0.000000000000043).
Heterogeneity arises from many factors including treatment delay, patient population, the effect measured, variants, and treatment regimens. The consistency of positive results across a wide variety of cases is remarkable. Heterogeneity is low in specific cases, for example early treatment mortality.
While many treatments have some level of efficacy, they do not replace vaccines and other measures to avoid infection. Only 29% of ivermectin studies show zero events in the treatment arm. Multiple approaches are required to protect everyone from all existing and future variants.
Many studies do not specify administration, or specify fasting. Administration with food may significantly increase plasma and tissue concentration.
All data to reproduce this paper and the sources are in the appendix. See [Bryant, Hill, Kory, Lawrie, Nardelli] for other meta analyses, all with similar results confirming effectiveness.
Resources: FLCCC, BIRD, WHO analysis
Show results for:
All studies
Exclusions
Mortality
Ventilation
ICU admission
Hospitalization
COVID-19 cases
Viral clearance
Peer reviewed
RCT mortality
All RCTs
00.250.50.7511.251.51.752+Kory et al.0.31[0.20-0.47]RRCIHill et al.0.25[0.12-0.52]Bryant et al.0.32[0.14-0.72]Lawrie et al.0.17[0.08-0.35]Nardelli et al.0.21[0.11-0.36]WHO (OR)0.19[0.09-0.36]ivmmeta0.26[0.15-0.44]Ivermectin meta analysis mortality resultsivmmeta.com 5/15/21Lower RiskIncreased Risk
ImprovementStudies AuthorsPatients
Early treatment 79% [63‑89%] 222022,510
Late treatment 46% [28‑60%] 191496,431
Prophylaxis 85% [75‑91%] 141088,789
Mortality 74% [56‑85%] 201797,361
RCTs only 66% [50‑76%] 282704,997
All studies 73% [65‑79%] 5545917,730
Evidence base used for other COVID-19 approvals
MedicationStudiesPatientsImprovement
Budesonide (UK)11,77917%
Remdesivir (USA)11,06331%
Casiri/imdevimab (USA)179966%
Ivermectin evidence5517,730 73% [65‑79%]
    
  
A
00.250.50.7511.251.51.752+Chowdhury (RCT)0.19[0.01-3.96]14mghosp.0/602/56OT​1 CT​2RRCIDose (4d)TreatmentControlEspitia-Hernandez0.03[0.01-0.11]12mgviral+0/287/7CT​2Carvallo0.12[0.01-1.06]36mgdeath1/333/12CT​2Mahmud (DB RCT)0.14[0.01-2.75]12mgdeath0/1833/183CT​2Cadegiani0.22[0.01-4.48]42mgdeath0/1102/137Ahmed (DB RCT)0.15[0.01-2.70]48mgsymptoms0/173/19Chaccour (DB RCT)0.47[0.19-1.16]28mgsymp. prob.1212Afsar0.08[0.00-1.32]48mgsymptoms0/377/53Babalola (DB RCT)0.36[0.10-1.27]24mgviral+4020OT​1Kirti (DB RCT)0.11[0.01-2.05]24mgdeath0/554/57Bukhari (RCT)0.18[0.07-0.46]12mgviral+4/4125/45Raad (SB RCT)0.14[0.01-2.70]14mghosp.0/503/50MD​3Mohan (DB RCT)0.38[0.08-1.75]28mgno recov.2/406/45Schwartz (DB RCT)0.30[0.03-2.76]36mghosp.1/473/42Elalfy0.13[0.06-0.27]36mgviral+7/6244/51CT​2López-Me.. (DB RCT)0.33[0.01-8.11]84mgdeath0/2001/198Roy0.94[0.52-1.93]n/arecov. time1415CT​2Chahla (CLUS. RCT)0.13[0.03-0.54]24mgno disch.2/11020/144Mourya0.11[0.05-0.25]48mgviral+5/5047/50Loue (QR)0.30[0.04-2.20]14mgdeath1/105/15Merino (QR)0.26[0.11-0.61]24mghosp.population-based cohortFaisal (RCT)0.32[0.14-0.72]48mgno recov.6/5019/50Tau​2 = 1.22; I​2 = 83.4%Early treatment0.21[0.11-0.37]29/1,249204/1,26179% improvementShouman (RCT)0.09[0.03-0.23]36mgsymp. case15/20359/101RRCIDose (1m)TreatmentControlCarvallo0.04[0.00-0.63]14mgcases0/13111/98CT​2Behera0.46[0.29-0.71]42mgcases41/117145/255Elgazzar (RCT)0.20[0.04-0.89]112mgcases2/10010/100Carvallo0.00[0.00-0.02]48mgcases0/788237/407CT​2Hellwig (ECO.)0.22[0.05-0.89]14mgcasesecologicalBernigaud0.01[0.00-0.10]84mgdeath0/69150/3,062CL​4Alam0.09[0.04-0.24]12mgcases4/5844/60Vallejos0.27[0.15-0.48]48mgcases13/38961/486MD​3Chahla (RCT)0.05[0.00-0.80]48mgcases0/11710/117CT​2Behera0.17[0.12-0.23]42mgcases45/2,199133/1,147Tanioka (ECO.)0.12[0.03-0.51]14mgdeathecologicalSeet (CLUS. RCT)0.50[0.33-0.76]12mgsevere case32/61764/619OT​1Morgenstern (PSM)0.20[0.01-4.15]56mghosp.0/2712/271Tau​2 = 0.58; I​2 = 83.8%Prophylaxis0.15[0.09-0.25]152/5,059926/3,73085% improvementAll studies0.17[0.11-0.26]181/6,3081,130/4,99183% improvementIvermectin COVID-19 early treatment and prophylaxis studiesivmmeta.com 5/15/211 OT: ivermectin vs. other treatment2 CT: study uses combined treatment3 MD: minimal detail available currently4 CL: control group size limited in totalsTau​2 = 0.97; I​2 = 89.8%; Z = 8.21 (p < 0.0001)Lower RiskIncreased Risk
    
  
B
00.250.50.7511.251.51.752+All studiesEarly treatmentmin, Q1, median, Q3, maxLower RiskIncreased Riskivmmeta.com 5/15/21
    
  
C
100+ 75 50 25 25 50 75 100 Chowdhuryhosp., p=0.23Espitia-Hernandezviral+, p<0.0001Carvallodeath, p=0.05Mahmuddeath, p=0.25Cadegianideath, p=0.50Ahmedsymptoms, p=0.09Chaccoursymp. prob., p<0.05Afsarsymptoms, p=0.04Babalolaviral+, p=0.11Kirtideath, p=0.12Bukhariviral+, p<0.0001Raadhosp., p=0.24Mohanno recov., p=0.27Schwartzhosp., p=0.34Elalfyviral+, p<0.0001López-Medinadeath, p=0.50Royrecov. time, p=0.87Chahlano disch., p=0.004Mouryaviral+, p<0.0001Louedeath, p=0.34Merinohosp., p<0.001Faisalno recov., p=0.005Early treatment% Lower Risk% Increased Riskivmmeta.com 5/15/21Probability results fromineffective treatmentDec 7 p<0.011 in 100Jan 9 p<0.0011 in 1 thousandFeb 12 p<0.00011 in 10 thousandMar 12 p<0.000011 in 100 thousandApr 17 p<0.0000011 in 1 million
    
  
D
100+ 75 50 25 25 50 75 100 Gorial, death, p=1.00Chowdhury, hosp., p=0.23Espitia-Hernandez, viral+, p<0.0001Shouman, symp. case, p<0.001Kishoria, no disch., p=1.00Podder, recov. time, p=0.34Carvallo, death, p=0.05Khan, death, p<0.05Chachar, no recov., p=0.50Soto-Becerra, death, p=0.01Mahmud, death, p=0.25Rajter, death, p=0.04Carvallo, cases, p<0.0001Hashim, death, p=0.27Behera, cases, p<0.0001Cadegiani, death, p=0.50Camprubí, ventilation, p=0.67Elgazzar, death, p<0.0001Elgazzar, cases, p=0.03Spoorthi, recov. time, p=0.03Carvallo, cases, p<0.0001Budhiraja, death, p=0.04Niaee, death, p=0.001Hellwig, cases, p<0.02Bernigaud, death, p=0.08Ahmed, symptoms, p=0.09Chaccour, symp. prob., p<0.05Afsar, symptoms, p=0.04Alam, cases, p<0.0001Vallejos, cases, p<0.0001Babalola, viral+, p=0.11Kirti, death, p=0.12Chahla, cases, p=0.002Okumuş, death, p=0.55Bukhari, viral+, p<0.0001Raad, hosp., p=0.24Shahbaznejad, death, p=1.00Mohan, no recov., p=0.27Lima-Morales, death, p<0.001Schwartz, hosp., p=0.34Behera, cases, p<0.001Elalfy, viral+, p<0.0001Gonzalez, death, p=1.00López-Medina, death, p=0.50Pott-Junior, ventilation, p=0.25Roy, recov. time, p=0.87Huvemek, no improv., p=0.28Tanioka, death, p=0.002Chahla, no disch., p=0.004Mourya, viral+, p<0.0001Seet, severe case, p=0.01Morgenstern, hosp., p=0.50Loue, death, p=0.34Merino, hosp., p<0.001Faisal, no recov., p=0.005All studies% Lower Risk% Increased Riskivmmeta.com 5/15/21Probability results fromineffective treatmentOct 9 p<0.011 in 100Nov 13 p<0.00011 in 10 thousandNov 18 p<0.000011 in 100 thousandNov 28 p<0.0000011 in 1 millionDec 15 p<0.00000011 in 10 millionFeb 121 in 1 billionApr 141 in 1 trillion
Figure 1. A. Random effects meta-analysis excluding late treatment. This plot shows pooled effects, analysis for individual outcomes is below, and more details on pooled effects can be found in the heterogeneity section. Simplified dosages are shown for comparison, these are the total dose in the first four days for treatment, and the monthly dose for prophylaxis, for a 70kg person. For full details see the appendix. B. Scatter plot showing the distribution of effects reported in early treatment studies and in all studies. C and D. Chronological history of all reported effects, with the probability that the observed frequency of positive results occurred due to random chance from an ineffective treatment.
Introduction
We analyze all significant studies concerning the use of ivermectin for COVID-19. Search methods, inclusion criteria, effect extraction criteria (more serious outcomes have priority), all individual study data, PRISMA answers, and statistical methods are detailed in Appendix 1. We present random effects meta-analysis results for all studies, for studies within each treatment stage, for mortality results, for COVID-19 case results, for viral clearance results, for peer-reviewed studies, for Randomized Controlled Trials (RCTs), and after exclusions.
We also perform a simple analysis of the distribution of study effects. If treatment was not effective, the observed effects would be randomly distributed (or more likely to be negative if treatment is harmful). We can compute the probability that the observed percentage of positive results (or higher) could occur due to chance with an ineffective treatment (the probability of >= k heads in n coin tosses, or the one-sided sign test / binomial test). Analysis of publication bias is important and adjustments may be needed if there is a bias toward publishing positive results.
Figure 2 shows stages of possible treatment for COVID-19. Prophylaxis refers to regularly taking medication before becoming sick, in order to prevent or minimize infection. Early Treatment refers to treatment immediately or soon after symptoms appear, while Late Treatment refers to more delayed treatment.
Figure 2. Treatment stages.
Results
Figure 3, 4, and 5 show results by treatment stage. Figure 6, 7, 8, 9, 10, 11, and 12 show forest plots for a random effects meta-analysis of all studies with pooled effects, and for studies reporting mortality results, ICU admission, mechanical ventilation, hospitalization, COVID-19 cases, and viral clearance results only. Figure 13 shows results for peer reviewed trials only. Table 1 summarizes the results.
Treatment timeNumber of studies reporting positive effects Total number of studiesPercentage of studies reporting positive effects Probability of an equal or greater percentage of positive results from an ineffective treatmentRandom effects meta-analysis results
Early treatment 22 22 100% 0.00000024 2.4e-07
1 in 4 million
79% improvement
RR 0.21 [0.11‑0.37] p < 0.0001
Late treatment 17 19 89.5% 0.00036 0.00036
1 in 3 thousand
46% improvement
RR 0.54 [0.40‑0.72] p < 0.0001
Prophylaxis 14 14 100% 0.000061 6.1e-05
1 in 16 thousand
85% improvement
RR 0.15 [0.09‑0.25] p < 0.0001
All studies 53 55 96.4% 0.000000000000043 4.3e-14
1 in 23 trillion
73% improvement
RR 0.27 [0.21‑0.35] p < 0.0001
Table 1. Results by treatment stage.
    
  
00.250.50.7511.251.51.752+All studiesLate treatmentEarly treatmentProphylaxismin, Q1, median, Q3, maxLower RiskIncreased Riskivmmeta.com 5/15/21
Figure 3. Results by treatment stage.
    
  
100+ 75 50 25 25 50 75 100 Chowdhuryhosp., p=0.23Espitia-Hernandezviral+, p<0.0001Carvallodeath, p=0.05Mahmuddeath, p=0.25Cadegianideath, p=0.50Ahmedsymptoms, p=0.09Chaccoursymp. prob., p<0.05Afsarsymptoms, p=0.04Babalolaviral+, p=0.11Kirtideath, p=0.12Bukhariviral+, p<0.0001Raadhosp., p=0.24Mohanno recov., p=0.27Schwartzhosp., p=0.34Elalfyviral+, p<0.0001López-Medinadeath, p=0.50Royrecov. time, p=0.87Chahlano disch., p=0.004Mouryaviral+, p<0.0001Louedeath, p=0.34Merinohosp., p<0.001Faisalno recov., p=0.005Early treatment% Lower Risk% Increased Riskivmmeta.com 5/15/21Probability results fromineffective treatmentDec 7 p<0.011 in 100Jan 9 p<0.0011 in 1 thousandFeb 12 p<0.00011 in 10 thousandMar 12 p<0.000011 in 100 thousandApr 17 p<0.0000011 in 1 million
    
  
100+ 75 50 25 25 50 75 100 Gorialdeath, p=1.00Kishoriano disch., p=1.00Podderrecov. time, p=0.34Khandeath, p<0.05Chacharno recov., p=0.50Soto-Becerradeath, p=0.01Rajterdeath, p=0.04Hashimdeath, p=0.27Camprubíventilation, p=0.67Elgazzardeath, p<0.0001Spoorthirecov. time, p=0.03Budhirajadeath, p=0.04Niaeedeath, p=0.001Okumuşdeath, p=0.55Shahbaznejaddeath, p=1.00Lima-Moralesdeath, p<0.001Gonzalezdeath, p=1.00Pott-Juniorventilation, p=0.25Huvemekno improv., p=0.28Late treatment% Lower Risk% Increased Riskivmmeta.com 5/15/21Probability results fromineffective treatmentOct 26 p<0.051 in 20Nov 14 p<0.011 in 100Mar 9 p<0.0011 in 1 thousand
Figure 4. Chronological history of early and late treatment results, with the probability that the observed frequency of positive results occurred due to random chance from an ineffective treatment.
100+ 75 50 25 25 50 75 100 Shoumansymp. case, p<0.001Carvallocases, p<0.0001Beheracases, p<0.0001Elgazzarcases, p=0.03Carvallocases, p<0.0001Hellwigcases, p<0.02Bernigauddeath, p=0.08Alamcases, p<0.0001Vallejoscases, p<0.0001Chahlacases, p=0.002Beheracases, p<0.001Taniokadeath, p=0.002Seetsevere case, p=0.01Morgensternhosp., p=0.50Prophylaxis% Lower Risk% Increased Riskivmmeta.com 5/15/21Probability results fromineffective treatmentNov 17 p<0.051 in 20Nov 28 p<0.011 in 100Jan 11 p<0.0011 in 1 thousandApr 16 p<0.00011 in 10 thousand
Figure 5. Chronological history of prophylaxis results.
    
  
00.250.50.7511.251.51.752+Chowdhury (RCT)0.19[0.01-3.96]14mghosp.0/602/56OT​1 CT​2RRCIDose (4d)TreatmentControlEspitia-Hernandez0.03[0.01-0.11]12mgviral+0/287/7CT​2Carvallo0.12[0.01-1.06]36mgdeath1/333/12CT​2Mahmud (DB RCT)0.14[0.01-2.75]12mgdeath0/1833/183CT​2Cadegiani0.22[0.01-4.48]42mgdeath0/1102/137Ahmed (DB RCT)0.15[0.01-2.70]48mgsymptoms0/173/19Chaccour (DB RCT)0.47[0.19-1.16]28mgsymp. prob.1212Afsar0.08[0.00-1.32]48mgsymptoms0/377/53Babalola (DB RCT)0.36[0.10-1.27]24mgviral+4020OT​1Kirti (DB RCT)0.11[0.01-2.05]24mgdeath0/554/57Bukhari (RCT)0.18[0.07-0.46]12mgviral+4/4125/45Raad (SB RCT)0.14[0.01-2.70]14mghosp.0/503/50MD​3Mohan (DB RCT)0.38[0.08-1.75]28mgno recov.2/406/45Schwartz (DB RCT)0.30[0.03-2.76]36mghosp.1/473/42Elalfy0.13[0.06-0.27]36mgviral+7/6244/51CT​2López-Me.. (DB RCT)0.33[0.01-8.11]84mgdeath0/2001/198Roy0.94[0.52-1.93]n/arecov. time1415CT​2Chahla (CLUS. RCT)0.13[0.03-0.54]24mgno disch.2/11020/144Mourya0.11[0.05-0.25]48mgviral+5/5047/50Loue (QR)0.30[0.04-2.20]14mgdeath1/105/15Merino (QR)0.26[0.11-0.61]24mghosp.population-based cohortFaisal (RCT)0.32[0.14-0.72]48mgno recov.6/5019/50Tau​2 = 1.22; I​2 = 83.4%Early treatment0.21[0.11-0.37]29/1,249204/1,26179% improvementGorial0.29[0.01-5.76]14mgdeath0/162/71RRCIDose (4d)TreatmentControlKishoria (RCT)1.08[0.57-2.02]12mgno disch.11/197/13Podder (RCT)0.84[0.55-1.12]14mgrecov. time3230Khan0.13[0.02-1.01]12mgdeath1/1159/133Chachar (RCT)0.90[0.44-1.83]36mgno recov.9/2510/25Soto-Becerra0.83[0.71-0.97]14mgdeath92/2031,438/2,630Rajter (PSM)0.54[0.27-0.99]14mgdeath13/9824/98Hashim (SB RCT)0.33[0.07-1.60]28mgdeath2/706/70CT​2Camprubí0.60[0.18-2.01]14mgventilation3/135/13Elgazzar (RCT)0.08[0.02-0.35]112mgdeath2/20024/200OT​1Spoorthi0.79[0.62-1.01]n/arecov. time5050CT​2Budhiraja0.01[0.00-0.15]n/adeath0/34103/942Niaee (DB RCT)0.18[0.06-0.55]28mgdeath4/12011/60Okumuş (DB RCT)0.67[0.27-1.64]56mgdeath6/309/30Shahbazn.. (DB RCT)2.97[0.13-70.51]14mgdeath1/350/34Lima-Morales0.22[0.12-0.41]12mgdeath15/48152/287CT​2Gonzalez (DB RCT)0.86[0.29-2.56]12mgdeath5/366/37Pott-Junior (RCT)0.15[0.01-1.93]14mgventilation1/271/4Huvemek (DB RCT)0.68[0.38-1.23]84mgno improv.13/5019/50Tau​2 = 0.18; I​2 = 66.9%Late treatment0.54[0.40-0.72]178/1,6541,726/4,77746% improvementShouman (RCT)0.09[0.03-0.23]36mgsymp. case15/20359/101RRCIDose (1m)TreatmentControlCarvallo0.04[0.00-0.63]14mgcases0/13111/98CT​2Behera0.46[0.29-0.71]42mgcases41/117145/255Elgazzar (RCT)0.20[0.04-0.89]112mgcases2/10010/100Carvallo0.00[0.00-0.02]48mgcases0/788237/407CT​2Hellwig (ECO.)0.22[0.05-0.89]14mgcasesecologicalBernigaud0.01[0.00-0.10]84mgdeath0/69150/3,062CL​4Alam0.09[0.04-0.24]12mgcases4/5844/60Vallejos0.27[0.15-0.48]48mgcases13/38961/486MD​3Chahla (RCT)0.05[0.00-0.80]48mgcases0/11710/117CT​2Behera0.17[0.12-0.23]42mgcases45/2,199133/1,147Tanioka (ECO.)0.12[0.03-0.51]14mgdeathecologicalSeet (CLUS. RCT)0.50[0.33-0.76]12mgsevere case32/61764/619OT​1Morgenstern (PSM)0.20[0.01-4.15]56mghosp.0/2712/271Tau​2 = 0.58; I​2 = 83.8%Prophylaxis0.15[0.09-0.25]152/5,059926/3,73085% improvementAll studies0.27[0.21-0.35]359/7,9622,856/9,76873% improvementAll 55 ivermectin COVID-19 studiesivmmeta.com 5/15/211 OT: ivermectin vs. other treatment2 CT: study uses combined treatment3 MD: minimal detail available currently4 CL: control group size limited in totalsTau​2 = 0.52; I​2 = 86.6%; Z = 9.69 (p < 0.0001)Lower RiskIncreased Risk
Figure 6. Random effects meta-analysis for all studies.