Results
Of the 969 screened patients, adequate data, baseline, and final ECG
were available in 194 patients for analysis, and this group constitutes
the study population. Table 2 depicts the clinical characteristics and
laboratory data of the participants. The entire group’s mean age was
55.4±13.8. The male participants’ proportion was slightly higher
(50.5%). The favipiravir group was older than the HQ group (59.0±13.2
vs. 51.5±13.4, p<0.001, respectively). There was no
significant difference in the gender distribution of the two groups
(p=0.77). History of coronary artery disease and hypertension were more
frequent in the favipiravir group than in the HQ group (13 [12.9%]
vs 4 [4.3%], p=0.03; 44 [43.6%] vs 27 [29.0%], p=0.03,
respectively). The diabetes mellitus rates of the two groups were
similar (26 [25.7%] vs. 17 [18.3%], p=0.21). The HQ group’s
white blood cell count was significantly higher than in the favipiravir
group (8.0±4.4 vs. 6.4±2.9, p=0.004, respectively). A significantly
higher level of alanine aminotransferase was found in the favipiravir
group as compared to the HQ group (22 [IQR:5-155]vs. 19
[IQR:7-83], p= 0.01.) Sodium and calcium levels were significantly
higher in the HQ group than the favipiravir group (140.0±3.3 vs.
138.0±3.8, p<0.001; 8.8±0.4 vs. 8.5±0.5, p<0.001,
respectively). The value of troponin and D-dimer in the HQ group was
significantly higher than those in the favipiravir group (6.4 [IQR:
0-57] vs 3.3 [IQR:0-133], p=0.003; 461 [IQR:74-26100] vs 269
[IQR:50-8076], p<0.001, respectively). Conversely,
C-reactive protein levels were significantly higher in the favipiravir
group as compared to the HQ group (31 [IQR:1-231] vs. 7.5
[IQR:2-104], p<0.001, respectively). The favipiravir
group’s hospitalization day was shorter than the HQ group (6.0±2.4 vs.
7.0±3.0, p=0.01, respectively). There was no significant difference in
hemoglobin, creatinine, and potassium levels between the two groups.
Table 3 describes the ECG evaluation results. The primary outcome
involving the arrhythmogenic adverse effects was non significantly
higher in the favipiravir group as compared to the HQ group (20
[19.8%] vs. 13 [13.9%], p=0.42, respectively) (Figure-2A). The
patients’ baseline HR, PR, and QTc intervals were 89±12 bpm, 151±15 ms,
and 402±20 ms, respectively (Figure-3). No significant difference was
found in the baseline HR, PR, and QTc interval among the groups (p=0.64;
p=0.63; p=0.14, respectively). The subjects’ final HR, PR, and QTc
interval were 78 ± 14 bpm, 161 ± 20 ms, 417 ± 27 ms, respectively
(Figure-3). The predischarge HR was significantly lower in the
favipiravir group than the HQ group (73±16 vs. 82±12, p<0.001,
respectively). The difference in the pretreatment and the post-treatment
heart rate (ΔHR) was significantly higher in the favipiravir group than
the HQ group (12 [IQR:-6—70] vs. 5 [IQR:-8—41)],
p<0.001, respectively) (Figure-2C). Also, patients with sinus
bradycardia were significantly higher in the favipiravir group than in
the HQ group (13 [12.9%] vs. 3 [3.2%], p=0.01, respectively)
(Figure-2B). Favipiravir was terminated in five symptomatic sinus
bradycardia patients in the favipiravir group. Subsequently, the
subjects’ heart rates raised without intervention in the follow-up.
Considering that patients with sinus bradycardia in the HQ group were
asymptomatic, the treatment regimen was continued. No significance was
found in the PR interval difference (ΔPR) among the groups (9
[IQR:-11—77] vs. 7 [IQR:-8—50], p=0.08, respectively). The
most extended PR interval was 240 ms, and treatment protocols were
completed without intervention in this patient. The prolongation from
baseline in QTc (ΔQTc) was similar between the groups (11
[IQR:-9—57] vs. 12 [IQR:-7—103], p=0.59, respectively)
(Figure-2D). The number of patients with prolonged QTc was higher in the
HQ group when compared with the favipiravir group ( 9 [9.7%] vs. 3
[3%], p=0.04, respectively). Four of the patients had a QTc
>500 ms during the medication in the HQ group, and the most
prolonged QTc interval was 534 ms. Of those, two patients’ QTc interval
shortened to <500 ms after HQ withdrawal. The other twos’ QTc
regressed to <500 ms with discontinuation of both HQ and
azithromycin. The other subjects with extended QTc intervals completed
the 5-day HQ cure without QTc prolongation >500 ms. In
contrast, none of the participants had a QTc >500 ms in the
favipiravir group. Furthermore, three patients had first-degree, and
five patients had a third-degree atrioventricular (AV) block in the
entire study (Table-3). A temporary pacemaker was implanted in whole
patients with complete AV block. In one, the pacemaker was converted
into permanent. Additionally, monomorphic non-sustained ventricular
tachycardia that was not progress in the follow-up was recorded in two
patients in the HQ group. TdP induced by QT prolongation, atrial
fibrillation, and arrhythmogenic death was not observed in the entire
cohort.