Supplementary material 7 to: Fluvoxamine for the treatment of COVID-19
Nyirenda JLZ, Sofroniou M, Toews I, Mikolajewska A, Lehane C, Monsef I, Abu-taha A, Maun A, Stegemann M, Schmucker C
https://doi.org/10.1002/14651858.CD015391
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Analyses
Analysis group 1 — Fluvoxamine plus standard care compared to placebo plus standard care for outpatients with mild COVID-19
Analysis or subgroup title
No. of studies
No. of participants
Statistical method
Effect size
1.1 All-cause mortality (at day 28)
2
1649
Risk Ratio (M-H, Random, 95% CI)
0.69 [0.38, 1.27]
1.2 All-cause hospital admission or death (before hospital admission)
2
1649
Risk Ratio (M-H, Random, 95% CI)
0.55 [0.16, 1.89]
1.3 Serious adverse events
2
1649
Risk Ratio (M-H, Random, 95% CI)
0.56 [0.15, 2.03]
1.4 Adverse events (any grade)
2
1649
Risk Ratio (M-H, Random, 95% CI)
1.06 [0.82, 1.37]
Figures and tables
Analysis 1.1: All-cause mortality (at day 28)
Study or Subgroup
Lenze 2020 (1)
TOGETHER 2021 (2)
Total (95% CI)
Total events:
Heterogeneity: Not applicable
Test for overall effect: Z = 1.18 (P = 0.24)
Test for subgroup differences: Not applicable
Fluvoxamine
Events
0
17
17
Total
80
741
821
Placebo
Events
0
25
25
Total
72
756
828
Weight
100.0%
100.0%
Risk Ratio
M-H, Random, 95% CI
Not estimable
0.69 [0.38 , 1.27]
0.69 [0.38 , 1.27]
Risk Ratio
M-H, Random, 95% CI
0.2
0.5
1
2
5
Favours fluvoxamine
Favours placebo
Risk of Bias
A
+
+
B
+
+
C
-
+
D
+
+
E
+
+
F
-
+
Footnotes
(1) Patient recruitment between 04/2020 and 08/2020. No vaccination was available at this time.
(2) Participant recruitment between January 2021 and August 2021. Vaccination was introduced during this time (6% of entire study population received at least 1 vaccine).
Risk of bias legend
(A) Bias arising from the randomization process
(B) Bias due to deviations from intended interventions
(C) Bias due to missing outcome data
(D) Bias in measurement of the outcome
(E) Bias in selection of the reported result
(F) Overall bias
Analysis 1.2: All-cause hospital admission or death (before hospital admission)
Study or Subgroup
Lenze 2020 (1)
TOGETHER 2021 (2)
Total (95% CI)
Total events:
Heterogeneity: Tau² = 0.49; Chi² = 1.82, df = 1 (P = 0.18); I² = 45%
Test for overall effect: Z = 0.94 (P = 0.35)
Test for subgroup differences: Not applicable
Fluvoxamine
Events
1
76
77
Total
80
741
821
Placebo
Events
5
99
104
Total
72
756
828
Weight
23.5%
76.5%
100.0%
Risk Ratio
M-H, Random, 95% CI
0.18 [0.02 , 1.50]
0.78 [0.59 , 1.04]
0.55 [0.16 , 1.89]
Risk Ratio
M-H, Random, 95% CI
0.2
0.5
1
2
5
Favours fluvoxamine
Favours placebo
Risk of Bias
A
+
+
B
+
+
C
+
+
D
+
+
E
+
+
F
+
+
Footnotes
(1) Participant recruitment between April 2020 and August 2020. No vaccination was available at this time.
(2) Participant recruitment between January 2021 and August 2021. Vaccination was introduced during this time (6% of entire study population received at least 1 vaccine).
Risk of bias legend
(A) Bias arising from the randomization process
(B) Bias due to deviations from intended interventions
(C) Bias due to missing outcome data
(D) Bias in measurement of the outcome
(E) Bias in selection of the reported result
(F) Overall bias
Analysis 1.3: Serious adverse events
Study or Subgroup
Lenze 2020 (1)
TOGETHER 2021 (2)
Total (95% CI)
Total events:
Heterogeneity: Tau² = 0.56; Chi² = 1.93, df = 1 (P = 0.16); I² = 48%
Test for overall effect: Z = 0.88 (P = 0.38)
Test for subgroup differences: Not applicable
Fluvoxamine
Events
1
77
78
Total
80
741
821
Standard care/placebo
Events
5
96
101
Total
72
756
828
Weight
25.0%
75.0%
100.0%
Risk Ratio
M-H, Random, 95% CI
0.18 [0.02 , 1.50]
0.82 [0.62 , 1.09]
0.56 [0.15 , 2.03]
Risk Ratio
M-H, Random, 95% CI
0.02
0.1
1
10
50
Favours fluvoxamine
Favours placebo
Risk of Bias
A
+
+
B
+
+
C
-
+
D
-
-
E
+
+
F
-
-
Footnotes
(1) Patient recruitment between 04/2020 and 08/2020. No vaccination was available at this time.
(2) Participant recruitment between January 2021 and August 2021. Vaccination was introduced during this time (6% of entire study population received at least 1 vaccine).
Risk of bias legend
(A) Bias arising from the randomization process
(B) Bias due to deviations from intended interventions
(C) Bias due to missing outcome data
(D) Bias in measurement of the outcome
(E) Bias in selection of the reported result
(F) Overall bias
Analysis 1.4: Adverse events (any grade)
Study or Subgroup
Lenze 2020 (1)
TOGETHER 2021 (2)
Total (95% CI)
Total events:
Heterogeneity: Tau² = 0.00; Chi² = 0.92, df = 1 (P = 0.34); I² = 0%
Test for overall effect: Z = 0.43 (P = 0.67)
Test for subgroup differences: Not applicable
Fluvoxamine
Events
11
92
103
Total
80
741
821
Standard care/placebo
Events
6
92
98
Total
72
756
828
Weight
7.6%
92.4%
100.0%
Risk Ratio
M-H, Random, 95% CI
1.65 [0.64 , 4.23]
1.02 [0.78 , 1.34]
1.06 [0.82 , 1.37]
Risk Ratio
M-H, Random, 95% CI
0.2
0.5
1
2
5
Favours fluvoxamine
Favours placebo
Risk of Bias
A
+
+
B
+
+
C
-
+
D
-
-
E
+
+
F
-
-
Footnotes
(1) Participant recruitment between April 2020 and August 2020. No vaccination was available at this time.
(2) Participant recruitment between January 2021 and August 2021. Vaccination was introduced during this time (6% of entire study population received at least 1 vaccine).
Risk of bias legend
(A) Bias arising from the randomization process
(B) Bias due to deviations from intended interventions
(C) Bias due to missing outcome data
(D) Bias in measurement of the outcome
(E) Bias in selection of the reported result
(F) Overall bias