A Randomized, Double-Blind, Multicenter Clinical Study Comparing the Efficacy and Safety of a Drug Combination of Lopinavir/Ritonavir-Azithromycin, Lopinavir/Ritonavir-Doxycycline, and Azithromycin-Hydroxychloroquine for Patients Diagnosed with Mild to Moderate COVID-19 Infections
Table 4
The adverse events observed in the research subjects during the study period.
Adverse events
Number of subjects (n)
Control
A
B
C
D
E
value
Nausea
1
1
Vomiting
1
Dizziness
2
1
1
Pruritus
1
Tachycardia
1
1
1
1
1
Hearing loss
1
Abdominal pain
1
1
1
Otalgia
1
Diarrhea
1
Taste loss
1
Number of patients with leukocytosis (platelet count >12,000 per μL), n (%)
Day 1
4 (3.4)
4 (3.1)
4 (3.2)
4 (3.3)
3 (2.3)
5 (3.9)
0.543
Day 7
1 (1.0)
0 (0.0)
2 (1.7)
1 (0.9)
1 (0.9)
2 (1.7)
0.891
Number of patients with thrombocytopenia (platelet count <150,000 per μL), n (%)
Day 1
2 (1.7)
0 (0.0)
1 (0.8)
0 (0.0)
0 (0.0)
3 (2.3)
0.331
Day 7
1 (1.0)
0 (0.0)
0 (0.0)
0 (0.0)
0 (0.0)
3 (2.6)
0.147
Number of patients with lymphocytopenia (lymphocyte count <1,500 per μL), n (%)
Day 1
6 (5.1)
6 (4.7)
12 (9.7)
10 (8.3)
12 (9.2)
10 (7.8)
0.559
Day 7
2 (1.9)
3 (2.4)
11 (9.3)
7 (6.1)
5 (4.4)
7 (6.0)
0.102
Number of patients with an increase of AST level, n (%)
Day 1
>33 U/L
36 (30.5)
31 (24.4)
22 (17.7)
23 (19.0)
31 (23.8)
35 (27.1)
0.168
Day 7
>33 U/L
19 (18.1)
13 (10.2)
8 (6.8)
20 (17.4)
13 (11.4)
22 (19.0)
0.029
Number of patients with an increase of ALT level, n (%)
Day 1
>50 U/L
27 (22.8)
27 (21.3)
22 (15.7)
19 (15.7)
34 (26.2)
35 (27.1)
0.185
Day 7
>50 U/L
21 (20.0)
19 (14.8)
12 (10.2)
21 (18.3)
14 (12.3)
21 (18.1)
0.270
Number of patients categorized according to serum creatinine level, n (%)
Day 1
>1.2 mg/dL
4 (3.4)
6 (4.8)
4 (3.2)
3 (2.5)
7 (5.4)
5 (3.9)
0.860
Day 7
>1.2 mg/dL
9 (8.6)
8 (6.3)
8 (6.8)
11 (9.6)
11 (9.6)
15 (12.9)
0.515
Median level of AST (U/L, min–max)
Day 1
27 (13–69)
25 (12–78)
26 (12–78)
25 (5–68)
26 (13–65)
26 (13–213)
Day 7
27 (17–49)
22 (14–55)
24 (14–58)
25 (6–92)
25 (14–53)
25 (16–73)
<0.05
Median level of ALT (U/L, min–max)
Day 1
34 (12–144)
32 (16–142)
32 (3–106)
31 (14–141)
36 (11–116)
35 (7–337)
Day 7
33 (16–106)
26 (12–140)
28 (2–137)
35 (14–205)
32 (2–91)
28 (8–128)
<0.05
Median level of creatinine serum (mg/dL, min–max)
Day 1
0.95 ± 0.12
0.93 (0.68–1.34)
0.96 ± 0.12
0.95 (0.77–1.34)
0.97 ± 0.14
0.97 ± 0.13
Day 7
0.99 ± 0.16
0.94 (0.67–1.37)
0.95 ± 0.13
0.96 (0.71–1.31)
1.02 ± 0.16
0.99 ± 0.15
<0.05
BUN level (mg/dL)
Day 1
10.7 ± 2.2
11.3 ± 1.8
11.1 (6.4–15.8)
11.2 (7.2–18.6)
11.1 ± 2.3
11.3 ± 2.1
Day 7
11.6 ± 2.5
11.9 ± 2.2
11.7 (7.0–21.3)
12.0 (8.3–20.1)
12.4 ± 2.5
13.0 ± 2.6
<0.05
Control group: 1 × 500 mg azithromycin per day; Group A: 2 × 200/50 mg lopinavir/ritonavir + 1 × 500 mg azithromycin per day; Group B: 2 × 200/50 mg lopinavir/ritonavir + 2 × 100 mg doxycycline per day; Group C: 2 × 100 mg hydroxychloroquine + 1 × 500 mg azithromycin per day; Group D: 2 × 400/100 mg lopinavir/ritonavir + 1 × 500 mg azithromycin per day; Group E: 2 × 400/100 mg lopinavir/ritonavir + 2 × 100 mg doxycycline per day; AST: aspartate aminotransferase serum; ALT: alanine aminotransferase serum. Normally distributed data presented in mean ± SD was analyzed by means of a paired t-test, whereas the other data was analyzed using a Wilcoxon signed-rank test. compared to day 1, compared to day 1, and compared to day 1.
