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.