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| Authors | Study design | Population | Intervention | Outcomes | Adverse effects of HCQ | Remark |
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| Molina et al., 2020 [12] | Prospective, nonrandomized, noncomparative open-labeled study | (i) 11 patients
(ii) Mean age 58.7 years | HCQ 600 mg/day for 10 days and + AZ 500 mg on day 1 and then 250 mg on days 2–5 | After 5 days,
(i) One died
(ii) Two transferred to the ICU | 1 patient discontinued drugs after 4 days due to QT interval prolongation from 405 ms before treatment to 460 and 470 ms under the combination | (i) Very small sample size
(ii) Risk factors for QTc prolongation were not addressed
(iii) The cause of death was not stated
(iv) The severity of the disease was not stated |
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| Million et al., 2020 [11] | Retrospective report | (i) 1061 patients: mean age 43.6 years (14–95 years)
(ii) The majority (95.0%) of patients had a low NEWS score | HCQ 200 mg TID for 10 days
HCQ+ AZ (500 mg on day 1 followed by 250 mg daily for the next 4 days) for at least 3 days | (i) Trans to ICU: 10
(ii) Death: 8 (due to respiratory failure) | (i) 25 reported mild adverse events. 3 patients discontinued treatment (due to abdominal pain, urticaria, erythematous, and bullous rash)
(ii) 9 patients had a QTc prolongation of more than 60 ms from baseline but no patient exceeded 500 ms. No rhythmic, cardiac events or sudden deaths. None showing torsade de pointe | Other drugs suspected to affect QT were systematically stopped |
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| Saleh et al., 2020 [26] | Prospective observational study | (i) 210 patients
(ii) Mean age: 58.5 ± 9.1yrs
(iii) Baseline QTc: 439.5 ± 24.8 | HCQ: 191 (95.0%) patients
(i) HCQ 400 mg PO BID for one day followed by 200 mg PO BID for 4 days ± AZ 500 mg PO or IV daily for 5 days to 119 (59.2%) patients | — | (i) TDPs due to ↑QTc = 0 patients
(ii) 18 patients: ↑QTc (≥500 ms)
(iii) Arrhythmogenic death = 0 patients
(iv) 7 (3.5%) patients discontinued HCQ ± AZ due to ↑QTc | (i) 8 patients (4.0%) had a baseline QTc> 500 ms
(ii) Receiving other QT-prolonging medications (81/210patients) |
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| Chorin et al., 2020 [27] | Multicenter retrospective study | 251 patients median age: 64 ± 13; baseline QTc (ms): 439 ± 29 | (i) HCQ 400 mg BID for one day followed by 200 mg BID for 4 days
HCQ+ AZ was given orally at a dose of 500 mg daily for 5 days | 44 (17.5%) died of respiratory or multiorgan failure | (i) 1 TdP developed after extreme QTc prolongation
(ii) 40 (15.9%) patients’ extreme QTc prolongation (>500 ms)
(iii) Change from baseline by > 60 ms, occurred in 51 (20.3%) patients.
(iv) 7 extreme QTcpts discontinued a drug | QTc-prolonging medications (78 patients) |
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| Chorin et al. 2020 [16] | Retrospective study | (i) 84 patients. Mean: 63 ± 15 years.
(ii) Baseline average of QTc: 435 ± 24 ms | (i) HCQ 400 mg BID on the first day, followed by 200 mg BID for 5 days
HCQ+ AZ 500 mg per day for 5 days | (i) 4 patients died from multiorgan failure, without evidence of arrhythmia and severe QTc prolongation
(ii) 64 remained in hospital at the end
(iii) 16 discharged | (i) 9 (11%) patients QTc prolonged to >500 ms
(ii) 10 (12%) patients had increased >60 ms
(iii) No tdp events | Receiving other suspected QTc prolonging drugs, 32 (39%) patients |
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| Bessière et al. 2020 [28] | Retrospective study | (i) 40 critically ill patients
(ii) median (IQR), 68 (58–74) yrs
(ii) Baseline QTc, median (IQR), ms 414 (392–428)
Excluded: QTc greater than 460 milliseconds | (i) HCQ 200 mg, bid/10 days) ± AZ 250 mg/d for 5 days
(ii) HCQ alone 22 (55%) patients
(iii) HCQ and AZ 18 (45%) patients | After treatment initiation, 30 (75%) patients required invasive mechanical ventilation | (i) After 2–5 days
QTc ≥500 ms or ΔQTc>60 ms (n = 14 patients)
(ii) No ventricular arrhythmia, including torsade de pointes
The antiviral treatment ceased before completion for 7 patients (17.5%) following ECG abnormalities | (i) Lack of generalizability beyond the ICU
(ii) Use of other QTc prolonging drugs (propofol, amiodarone, ciprofloxacin, and ondansetron), 20 (50%) patients |
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| Gautret et al. 2020 [8] | Prospective observational study | (i) 80 patients
(ii) Median: 52.5 (18–88) years
(iii) 92% low NEWS score
(iv) QTc prolonging medical conditions and drugs excluded at baseline | HCQ 200 mg of PO, TID for 10 days.
HCQ + azithromycin 500 mg on D1 followed by 250 mg per day for the next 4 days | Transfer to ICU: 3 (3.8%), where 2 were improved and 1 returned to IDW. Death: 1 (1.2%). Discharged/improved: 65 (81.2%); currently hospitalized: 14 (1 in ICU and 13 in IDW) | (i) Possible adverse events: 7 (8.7%)
(ii) Nausea or vomiting: 2 (2.5%)
(iii) Diarrhea 4 (5.0%)
Blurred vision: 1 (1.2%) | (i) Patients followed-up for at least six days were included in analysis
(ii) Max. 10 days
Lost to follow-up patients were not known |
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| Cipiriani et al. 2020 [34] | Observational case-control study | (i) 22 patients
(ii) Median age: 64
(iii) Baseline QTc-interval: 426 (403–447) ms
Controls: 34 health individuals, matched for age and sex | HCQ 200 mg BID and AZ 500 mg, once daily for at least three days | — | (i) QTc prolongation (QTc ≥ 480 ms) after HCQ treatment: 4 (18%) patients, of which 1 patient developed > 500 ms
(ii) No cases of syncope, fatal arrhythmias, and sudden cardiac death | (i) Conditions predisposing to QTc prolongation including medications were excluded
(ii) There was a significant QTc difference after HCQ initiation (426 vs. 450 ms, p = 0.02)
(iii) Mean of QTc of patients was 453 (439–477) ms while of controls was 407 (397–418); P value <0.001. |
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