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34 colchicine COVID-19 controlled studies, 17 RCTs
68% improvement
for early treatment, RR
0.32
[0.15-0.67]
https://c19colchicine.com/meta.html
0
0.5
1
1.5+
All studies
40%
34
22,738
Improvement, Studies, Patients
Relative Risk
Mortality
42%
29
21,010
Ventilation
43%
6
12,814
ICU admission
29%
5
815
Hospitalization
23%
10
6,815
Progression
81%
3
289
Recovery
30%
9
12,419
Cases
-73%
1
1,278
RCTs
22%
17
19,059
RCT mortality
7%
14
18,677
Peer-reviewed
42%
31
22,217
Prophylaxis
26%
3
1,278
Early
68%
1
0
Late
39%
30
21,460
Colchicine for COVID-19
c19colchicine.com Aug 2022
Favors colchicine
Favors control
after exclusions
• Statistically significant improvements are seen for
mortality ,
ICU admission ,
hospitalization , and
recovery . 21 studies from 21 independent teams in 13 different countries show statistically significant
improvements in isolation (12 for the most serious outcome).
• Results are robust — in exclusion sensitivity analysis 24 of 34
studies must be excluded to avoid finding statistically significant efficacy
in pooled analysis.
0
0.5
1
1.5+
All studies
40%
34
22,738
Improvement, Studies, Patients
Relative Risk
Mortality
42%
29
21,010
Ventilation
43%
6
12,814
ICU admission
29%
5
815
Hospitalization
23%
10
6,815
Progression
81%
3
289
Recovery
30%
9
12,419
Cases
-73%
1
1,278
RCTs
22%
17
19,059
RCT mortality
7%
14
18,677
Peer-reviewed
42%
31
22,217
Prophylaxis
26%
3
1,278
Early
68%
1
0
Late
39%
30
21,460
Colchicine for COVID-19
c19colchicine.com Aug 2022
Favors colchicine
Favors control
after exclusions
• RCT results are less favorable, however they are dominated by the very late stage RECOVERY RCT,
for which the results are not generalizable to earlier usage.
• While
many treatments have some level
of efficacy, they do not replace vaccines and other measures to avoid
infection.
Only 15% of colchicine
studies show zero events in the treatment arm.
Multiple treatments are typically used
in combination, and
other treatments
may be more effective.
• No treatment, vaccine, or intervention is 100%
available and effective for all variants. All practical, effective, and safe
means should be used.
Denying the efficacy of treatments increases mortality, morbidity, collateral
damage, and endemic risk.
• All data to reproduce this paper and
sources are in the
appendix .
Other meta analyses for colchicine can be found in
[Rai , Yasmin , Zein ] , showing significant improvements for mortality and severity.
Highlights
We show traditional outcome specific analyses and combined
evidence from all studies, incorporating treatment delay, a primary
confounding factor in COVID-19 studies.
A
0
0.25
0.5
0.75
1
1.25
1.5
1.75
2+
Hunt
68%
0.32 [0.15-0.67]
death
Improvement, RR [CI]
Treatment
Control
Tau2 = 0.00, I2 = 0.0%, p = 0.0006
Early treatment
68%
0.32 [0.15-0.67]
68% improvement
Deftereos (RCT)
77%
0.23 [0.03-1.97]
death
1/55
4/50
Improvement, RR [CI]
Treatment
Control
Lopes (DB RCT)
80%
0.20 [0.01-4.03]
death
0/36
2/36
Brunetti (PSM)
73%
0.27 [0.08-0.89]
death
3/33
11/33
Scarsi
85%
0.15 [0.06-0.37]
death
122 (n)
140 (n)
Salehzadeh (RCT)
23%
0.77 [0.66-0.90]
hosp. time
50 (n)
50 (n)
Pinzón
35%
0.65 [0.34-1.21]
death
14/145
23/156
Sandhu
42%
0.58 [0.40-0.85]
death
16/34
63/78
Rodriguez-Nava
6%
0.94 [0.61-1.47]
death
16/52
85/261
Mahale
-7%
1.07 [0.59-1.96]
death
11/39
25/95
Valerio Pas.. (ICU)
23%
0.77 [0.31-1.94]
death
5/35
12/30
ICU patients CT1
Tardif (DB RCT)
44%
0.56 [0.19-1.67]
death
5/2,235
9/2,253
Mareev
80%
0.20 [0.01-4.01]
death
0/21
2/22
García-Posada
57%
0.43 [0.16-0.84]
death
48/99
59/110
CT1
Manenti (PSW)
76%
0.24 [0.09-0.67]
death
71 (n)
70 (n)
Mostafaie (RCT)
83%
0.17 [0.02-1.34]
death
1/60
6/60
CT1
Recovery C.. (RCT)
-1%
1.01 [0.93-1.10]
death
1,173/5,610
1,190/5,730
Hueda-Zavaleta
54%
0.46 [0.23-0.91]
death
10/50
109/301
Kevorkian
96%
0.04 [0.01-0.21]
progression
28 (n)
40 (n)
CT1
Gaitán-Dua.. (RCT)
22%
0.78 [0.44-1.36]
death
22/153
28/161
CT1
Pascual-Fi.. (RCT)
80%
0.20 [0.01-4.03]
death
0/52
2/51
Dorward (RCT)
70%
0.30 [0.01-7.37]
death
0/156
1/120
Absalón-.. (DB RCT)
29%
0.71 [0.21-2.40]
death
4/56
6/60
Diaz (RCT)
12%
0.88 [0.70-1.12]
death
131/640
142/639
Alsultan (RCT)
36%
0.64 [0.20-2.07]
death
3/14
7/21
Karakaş
13%
0.87 [0.46-1.64]
death
16/165
19/171
Pourdowlat (RCT)
73%
0.27 [0.11-0.71]
hosp.
5/102
18/100
Gorial (RCT)
67%
0.33 [0.04-3.14]
death
1/80
3/80
Pimenta B.. (RCT)
79%
0.21 [0.01-4.05]
death
0/14
2/16
Jalal (RCT)
24%
0.76 [0.62-0.93]
hosp. time
36 (n)
44 (n)
Cecconi (DB RCT)
29%
0.71 [0.28-1.79]
death
7/119
10/120
Tau2 = 0.10, I2 = 73.5%, p < 0.0001
Late treatment
39%
0.61 [0.51-0.73]
1,492/10,362
1,838/11,098
39% improvement
Monserrat V.. (PSM)
80%
0.20 [0.02-0.93]
death
n/a
n/a
Improvement, RR [CI]
Treatment
Control
Topless
23%
0.77 [0.56-1.07]
death
Oztas
-406%
5.06 [0.59-43.2]
hosp.
5/635
1/643
Tau2 = 0.86, I2 = 69.7%, p = 0.66
Prophylaxis
26%
0.74 [0.21-2.66]
5/635
1/643
26% improvement
All studies
40%
0.60 [0.50-0.71]
1,497/10,997
1,839/11,741
40% improvement
34 colchicine COVID-19 studies
c19colchicine.com Aug 2022
Tau2 = 0.11, I2 = 73.7%, p < 0.0001
Effect extraction pre-specified (most serious outcome, see appendix)
1 CT: study uses combined treatment
Favors colchicine
Favors control
B
C
Figure 1. A. Random effects
meta-analysis. This plot shows pooled effects, discussion can be found in the heterogeneity section,
and results for specific outcomes can be found in the individual outcome analyses.
Effect extraction is pre-specified, using the most serious outcome reported.
For details of effect extraction see the
appendix .
B. Scatter plot showing the
distribution of effects reported in studies.
C. History of all reported
effects (chronological within treatment stages).
Introduction
We analyze all significant studies
concerning the use of
colchicine
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 individual outcomes, for
peer-reviewed studies, for Randomized Controlled Trials (RCTs), and after
exclusions.
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.
Results
Figure 3 shows a visual overview of the results, with details in
Table 1 and
Table 2 .
Figure
4 ,
5 ,
6 ,
7 ,
8 ,
9 ,
10 ,
11 , and
12
show forest plots for a random effects meta-analysis of
all studies with pooled effects, mortality results, ventilation, ICU admission, hospitalization, progression, recovery, cases, and peer reviewed studies.
0
0.5
1
1.5+
ALL STUDIES
MORTALITY
VENTILATION
ICU ADMISSION
HOSPITALIZATION
PROGRESSION
RECOVERY
CASES
RANDOMIZED CONTROLLED TRIALS
RCT MORTALITY
PEER-REVIEWED
After Exclusions
ALL STUDIES
All
Prophylaxis
Early
Late
Colchicine for COVID-19
C19COLCHICINE.COM AUG 2022
Treatment time Number of studies reporting positive effects
Total number of studies Percentage of studies reporting positive effects
Random effects meta-analysis results
Early treatment
1
1
100%
68% improvement
RR 0.32 [0.15‑0.67]
p = 0.0029
Late treatment
28
30
93.3%
39% improvement
RR 0.61 [0.51‑0.73]
p < 0.0001
Prophylaxis
2
3
66.7%
26% improvement
RR 0.74 [0.21‑2.66]
p = 0.66
All studies
31
34
91.2%
40% improvement
RR 0.60 [0.50‑0.71]
p < 0.0001
Table 1. Results by treatment stage.
0
0.25
0.5
0.75
1
1.25
1.5
1.75
2+
Hunt
68%
0.32 [0.15-0.67]
death
Improvement, RR [CI]
Treatment
Control
Tau2 = 0.00, I2 = 0.0%, p = 0.0006
Early treatment
68%
0.32 [0.15-0.67]
68% improvement
Deftereos (RCT)
77%
0.23 [0.03-1.97]
death
1/55
4/50
Improvement, RR [CI]
Treatment
Control
Lopes (DB RCT)
80%
0.20 [0.01-4.03]
death
0/36
2/36
Brunetti (PSM)
73%
0.27 [0.08-0.89]
death
3/33
11/33
Scarsi
85%
0.15 [0.06-0.37]
death
122 (n)
140 (n)
Salehzadeh (RCT)
23%
0.77 [0.66-0.90]
hosp. time
50 (n)
50 (n)
Pinzón
35%
0.65 [0.34-1.21]
death
14/145
23/156
Sandhu
42%
0.58 [0.40-0.85]
death
16/34
63/78
Rodriguez-Nava
6%
0.94 [0.61-1.47]
death
16/52
85/261
Mahale
-7%
1.07 [0.59-1.96]
death
11/39
25/95
Valerio Pas.. (ICU)
23%
0.77 [0.31-1.94]
death
5/35
12/30
ICU patients CT1
Tardif (DB RCT)
44%
0.56 [0.19-1.67]
death
5/2,235
9/2,253
Mareev
80%
0.20 [0.01-4.01]
death
0/21
2/22
García-Posada
57%
0.43 [0.16-0.84]
death
48/99
59/110
CT1
Manenti (PSW)
76%
0.24 [0.09-0.67]
death
71 (n)
70 (n)
Mostafaie (RCT)
83%
0.17 [0.02-1.34]
death
1/60
6/60
CT1
Recovery C.. (RCT)
-1%
1.01 [0.93-1.10]
death
1,173/5,610
1,190/5,730
Hueda-Zavaleta
54%
0.46 [0.23-0.91]
death
10/50
109/301
Kevorkian
96%
0.04 [0.01-0.21]
progression
28 (n)
40 (n)
CT1
Gaitán-Dua.. (RCT)
22%
0.78 [0.44-1.36]
death
22/153
28/161
CT1
Pascual-Fi.. (RCT)
80%
0.20 [0.01-4.03]
death
0/52
2/51
Dorward (RCT)
70%
0.30 [0.01-7.37]
death
0/156
1/120
Absalón-.. (DB RCT)
29%
0.71 [0.21-2.40]
death
4/56
6/60
Diaz (RCT)
12%
0.88 [0.70-1.12]
death
131/640
142/639
Alsultan (RCT)
36%
0.64 [0.20-2.07]
death
3/14
7/21
Karakaş
13%
0.87 [0.46-1.64]
death
16/165
19/171
Pourdowlat (RCT)
73%
0.27 [0.11-0.71]
hosp.
5/102
18/100
Gorial (RCT)
67%
0.33 [0.04-3.14]
death
1/80
3/80
Pimenta B.. (RCT)
79%
0.21 [0.01-4.05]
death
0/14
2/16
Jalal (RCT)
24%
0.76 [0.62-0.93]
hosp. time
36 (n)
44 (n)
Cecconi (DB RCT)
29%
0.71 [0.28-1.79]
death
7/119
10/120
Tau2 = 0.10, I2 = 73.5%, p < 0.0001
Late treatment
39%
0.61 [0.51-0.73]
1,492/10,362
1,838/11,098
39% improvement
Monserrat V.. (PSM)
80%
0.20 [0.02-0.93]
death
n/a
n/a
Improvement, RR [CI]
Treatment
Control
Topless
23%
0.77 [0.56-1.07]
death
Oztas
-406%
5.06 [0.59-43.2]
hosp.
5/635
1/643
Tau2 = 0.86, I2 = 69.7%, p = 0.66
Prophylaxis
26%
0.74 [0.21-2.66]
5/635
1/643
26% improvement
All studies
40%
0.60 [0.50-0.71]
1,497/10,997
1,839/11,741
40% improvement
34 colchicine COVID-19 studies
c19colchicine.com Aug 2022
Tau2 = 0.11, I2 = 73.7%, p < 0.0001
Effect extraction pre-specified (most serious outcome, see appendix)
1 CT: study uses combined treatment
Favors colchicine
Favors control
Figure 4. Random effects meta-analysis for all studies with pooled effects.
This plot shows pooled effects, discussion can be found in the heterogeneity section,
and results for specific outcomes can be found in the individual outcome analyses.
Effect extraction is pre-specified, using the most serious outcome reported.
For details of effect extraction see the
appendix .
0
0.25
0.5
0.75
1
1.25
1.5
1.75
2+
Hunt
68%
0.32 [0.15-0.67]
Improvement, RR [CI]
Treatment
Control
Tau2 = 0.00, I2 = 0.0%, p = 0.0006
Early treatment
68%
0.32 [0.15-0.67]
68% improvement
Deftereos (RCT)
77%
0.23 [0.03-1.97]
1/55
4/50
Improvement, RR [CI]
Treatment
Control
Lopes (DB RCT)
80%
0.20 [0.01-4.03]
0/36
2/36
Brunetti (PSM)
73%
0.27 [0.08-0.89]
3/33
11/33
Scarsi
85%
0.15 [0.06-0.37]
122 (n)
140 (n)
Pinzón
35%
0.65 [0.34-1.21]
14/145
23/156
Sandhu
42%
0.58 [0.40-0.85]
16/34
63/78
Rodriguez-Nava
6%
0.94 [0.61-1.47]
16/52
85/261
Mahale
-7%
1.07 [0.59-1.96]
11/39
25/95
Valerio Pas.. (ICU)
23%
0.77 [0.31-1.94]
5/35
12/30
ICU patients CT1
Tardif (DB RCT)
44%
0.56 [0.19-1.67]
5/2,235
9/2,253
Mareev
80%
0.20 [0.01-4.01]
0/21
2/22
García-Posada
57%
0.43 [0.16-0.84]
48/99
59/110
CT1
Manenti (PSW)
76%
0.24 [0.09-0.67]
71 (n)
70 (n)
Mostafaie (RCT)
83%
0.17 [0.02-1.34]
1/60
6/60
CT1
Recovery C.. (RCT)
-1%
1.01 [0.93-1.10]
1,173/5,610
1,190/5,730
Hueda-Zavaleta
54%
0.46 [0.23-0.91]
10/50
109/301
Gaitán-Dua.. (RCT)
22%
0.78 [0.44-1.36]
22/153
28/161
CT1
Pascual-Fi.. (RCT)
80%
0.20 [0.01-4.03]
0/52
2/51
Dorward (RCT)
70%
0.30 [0.01-7.37]
0/156
1/120
Absalón-.. (DB RCT)
29%
0.71 [0.21-2.40]
4/56
6/60
Diaz (RCT)
12%
0.88 [0.70-1.12]
131/640
142/639
Alsultan (RCT)
36%
0.64 [0.20-2.07]
3/14
7/21
Karakaş
13%
0.87 [0.46-1.64]
16/165
19/171
Gorial (RCT)
67%
0.33 [0.04-3.14]
1/80
3/80
Pimenta B.. (RCT)
79%
0.21 [0.01-4.05]
0/14
2/16
Cecconi (DB RCT)
29%
0.71 [0.28-1.79]
7/119
10/120
Tau2 = 0.13, I2 = 71.6%, p < 0.0001
Late treatment
40%
0.60 [0.48-0.75]
1,487/10,146
1,820/10,864
40% improvement
Monserrat V.. (PSM)
80%
0.20 [0.02-0.93]
n/a
n/a
Improvement, RR [CI]
Treatment
Control
Topless
23%
0.77 [0.56-1.07]
Tau2 = 0.64, I2 = 71.1%, p = 0.24
Prophylaxis
53%
0.47 [0.13-1.67]
53% improvement
All studies
42%
0.58 [0.47-0.72]
1,487/10,146
1,820/10,864
42% improvement
29 colchicine COVID-19 mortality results
c19colchicine.com Aug 2022
Tau2 = 0.14, I2 = 72.7%, p < 0.0001
1 CT: study uses combined treatment
Favors colchicine
Favors control
Figure 5. Random effects meta-analysis for mortality results.
0
0.25
0.5
0.75
1
1.25
1.5
1.75
2+
Deftereos (RCT)
82%
0.18 [0.02-1.50]
1/55
5/50
Improvement, RR [CI]
Treatment
Control
Sandhu
53%
0.47 [0.33-0.67]
16/34
68/68
Tardif (DB RCT)
47%
0.53 [0.25-1.09]
11/2,235
21/2,253
Recovery C.. (RCT)
-18%
1.18 [0.99-1.40]
259/3,815
228/3,962
Pascual-Fi.. (RCT)
80%
0.20 [0.01-4.03]
0/52
2/51
Cecconi (DB RCT)
50%
0.50 [0.18-1.43]
5/119
10/120
Tau2 = 0.34, I2 = 82.5%, p = 0.075
Late treatment
43%
0.57 [0.31-1.06]
292/6,310
334/6,504
43% improvement
All studies
43%
0.57 [0.31-1.06]
292/6,310
334/6,504
43% improvement
6 colchicine COVID-19 mechanical ventilation results
c19colchicine.com Aug 2022
Tau2 = 0.34, I2 = 82.5%, p = 0.075
Favors colchicine
Favors control
Figure 6. Random effects meta-analysis for ventilation.
0
0.25
0.5
0.75
1
1.25
1.5
1.75
2+
Lopes (DB RCT)
50%
0.50 [0.10-2.56]
2/36
4/36
Improvement, RR [CI]
Treatment
Control
Valerio Pas.. (ICU)
40%
0.60 [0.38-0.95]
35 (n)
30 (n)
ICU patients CT1
Pascual-Fi.. (RCT)
51%
0.49 [0.09-2.56]
2/52
4/51
Karakaş
16%
0.84 [0.55-1.29]
30/165
37/171
Cecconi (DB RCT)
21%
0.79 [0.38-1.67]
11/119
14/120
Tau2 = 0.00, I2 = 0.0%, p = 0.018
Late treatment
29%
0.71 [0.54-0.94]
45/407
59/408
29% improvement
All studies
29%
0.71 [0.54-0.94]
45/407
59/408
29% improvement
5 colchicine COVID-19 ICU results
c19colchicine.com Aug 2022
Tau2 = 0.00, I2 = 0.0%, p = 0.018
1 CT: study uses combined treatment
Favors colchicine
Favors control
Figure 7. Random effects meta-analysis for ICU admission.
0
0.25
0.5
0.75
1
1.25
1.5
1.75
2+
Lopes (DB RCT)
22%
0.78 [0.64-0.94]
hosp. time
36 (n)
36 (n)
Improvement, RR [CI]
Treatment
Control
Salehzadeh (RCT)
23%
0.77 [0.66-0.90]
hosp. time
50 (n)
50 (n)
Tardif (DB RCT)
20%
0.80 [0.61-1.03]
hosp.
101/2,235
128/2,253
Mareev
26%
0.74 [0.53-1.04]
hosp. time
21 (n)
22 (n)
Mostafaie (RCT)
35%
0.65 [0.53-0.81]
hosp. time
59 (n)
54 (n)
CT1
Pascual-Fi.. (RCT)
-15%
1.15 [0.87-1.51]
hosp. time
52 (n)
51 (n)
Karakaş
25%
0.75 [0.65-0.87]
hosp. time
165 (n)
171 (n)
Pourdowlat (RCT)
73%
0.27 [0.11-0.71]
hosp.
5/102
18/100
Jalal (RCT)
24%
0.76 [0.62-0.93]
hosp. time
36 (n)
44 (n)
Tau2 = 0.01, I2 = 47.1%, p < 0.0001
Late treatment
23%
0.77 [0.69-0.85]
106/2,756
146/2,781
23% improvement
Oztas
-406%
5.06 [0.59-43.2]
hosp.
5/635
1/643
Improvement, RR [CI]
Treatment
Control
Tau2 = 0.00, I2 = 0.0%, p = 0.14
Prophylaxis
-406%
5.06 [0.59-43.2]
5/635
1/643
-406% improvement
All studies
23%
0.77 [0.69-0.86]
111/3,391
147/3,424
23% improvement
10 colchicine COVID-19 hospitalization results
c19colchicine.com Aug 2022
Tau2 = 0.01, I2 = 50.2%, p < 0.0001
1 CT: study uses combined treatment
Favors colchicine
Favors control
Figure 8. Random effects meta-analysis for hospitalization.