Dataset Information

Lack of efficacy of hydroxychloroquine and azithromycin in patients hospitalized for COVID-19 pneumonia: A retrospective study.

ABSTRACT:

Background

Hydroxychloroquine combined with azithromycin (HCQ/AZI) has initially been used against coronavirus disease-2019 (COVID-19). In this retrospective study, we assessed the clinical effects of HCQ/AZI, with a 28-days follow-up.

Methods

In a registry-study which included patients hospitalized for COVID-19 between March 15 and April 2, 2020, we compared patients who received HCQ/AZI to those who did not, regarding a composite outcome of mortality and mechanical ventilation with a 28-days follow-up. QT was monitored for patients treated with HCQ/AZI. Were excluded patients in intensive care units, palliative care and ventilated within 24 hours of admission. Three analyses were performed to adjust for selection bias: propensity score matching, multivariable survival, and inverse probability score weighting (IPSW) analyses.

Results

Overall, 203 patients were included: 60 patients treated by HCQ/AZI and 143 control patients. During the 28-days follow-up, 32 (16.3%) patients presented the primary outcome and 23 (12.3%) patients died. Propensity-score matching identified 52 unique pairs of patients with similar characteristics. In the matched cohort (n = 104), HCQ/AZI was not associated with the primary composite outcome (log-rank p-value = 0.16). In the overall cohort (n = 203), survival and IPSW analyses also found no benefit from HCQ/AZI. In the HCQ/AZI group, 11 (18.3%) patients prolonged QT interval duration, requiring treatment cessation.

Conclusions

HCQ/AZI combination therapy was not associated with lower in-hospital mortality and mechanical ventilation rate, with a 28-days follow-up. In the HCQ/AZI group, 18.3% of patients presented a prolonged QT interval requiring treatment cessation, however, control group was not monitored for this adverse event, making comparison impossible.

SUBMITTER: Saib A

PROVIDER: S-EPMC8189518 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:RationaleThe COVID-19 pandemic struck an immunologically naïve, globally interconnected population. In the face of a new infectious agent causing acute respiratory failure for which there were no known effective therapies, rapid, often pragmatic trials were necessary to evaluate potential treatments, frequently starting with medications that are already marketed for other indications. Early in the pandemic, hydroxychloroquine and azithromycin were two such candidates.ObjectiveAssess the relative efficacy of hydroxychloroquine and azithromycin among hospitalized patients with COVID-19.MethodsWe performed a randomized clinical trial of hydroxychloroquine vs. azithromycin among hospitalized patients with COVID-19. Treatment was 5 days of study medication. The primary endpoint was the COVID Ordinal Outcomes scale at day 14. Secondary endpoints included hospital-, ICU-, and ventilator-free days at day 28. The trial was stopped early after enrollment of 85 patients when a separate clinical trial concluded that a clinically important effect of hydroxychloroquine over placebo was definitively excluded. Comparisons were made a priori using a proportional odds model from a Bayesian perspective.ResultsWe enrolled 85 patients at 13 hospitals over 11 weeks. Adherence to study medication was high. The estimated odds ratio for less favorable status on the ordinal scale for hydroxychloroquine vs. azithromycin from the primary analysis was 1.07, with a 95% credible interval from 0.63 to 1.83 with a posterior probability of 60% that hydroxychloroquine was worse than azithryomycin. Secondary outcomes displayed a similar, slight preference for azithromycin over hydroxychloroquine. QTc prolongation was rare and did not differ between groups. The twenty safety outcomes were similar between arms with the possible exception of post-randomization onset acute kidney injury, which was more common with hydroxychloroquine (15% vs. 0%). Patients in the hydroxychloroquine arm received remdesivir more often than in the azithromycin arm (19% vs. 2%). There was no apparent association between remdesivir use and acute kidney injury.ConclusionsWhile early termination limits the precision of our results, we found no suggestion of substantial efficacy for hydroxychloroquine over azithromycin. Acute kidney injury may be more common with hydroxychloroquine than azithromycin, although this may be due to the play of chance. Differential use of remdesivir may have biased our results in favor of hydroxychloroquine. Our results are consistent with conclusions from other trials that hydroxychloroquine cannot be recommended for inpatients with COVID-19; azithromycin may merit additional investigation.Clinical trial registrationThis trial was prospectively registered (NCT04329832) before enrollment of the first patient.

Project description:BackgroundHydroxychloroquine and chloroquine have been proposed as treatments for coronavirus disease 2019 (Covid-19) on the basis of in vitro activity and data from uncontrolled studies and small, randomized trials.MethodsIn this randomized, controlled, open-label platform trial comparing a range of possible treatments with usual care in patients hospitalized with Covid-19, we randomly assigned 1561 patients to receive hydroxychloroquine and 3155 to receive usual care. The primary outcome was 28-day mortality.ResultsThe enrollment of patients in the hydroxychloroquine group was closed on June 5, 2020, after an interim analysis determined that there was a lack of efficacy. Death within 28 days occurred in 421 patients (27.0%) in the hydroxychloroquine group and in 790 (25.0%) in the usual-care group (rate ratio, 1.09; 95% confidence interval [CI], 0.97 to 1.23; P = 0.15). Consistent results were seen in all prespecified subgroups of patients. The results suggest that patients in the hydroxychloroquine group were less likely to be discharged from the hospital alive within 28 days than those in the usual-care group (59.6% vs. 62.9%; rate ratio, 0.90; 95% CI, 0.83 to 0.98). Among the patients who were not undergoing mechanical ventilation at baseline, those in the hydroxychloroquine group had a higher frequency of invasive mechanical ventilation or death (30.7% vs. 26.9%; risk ratio, 1.14; 95% CI, 1.03 to 1.27). There was a small numerical excess of cardiac deaths (0.4 percentage points) but no difference in the incidence of new major cardiac arrhythmia among the patients who received hydroxychloroquine.ConclusionsAmong patients hospitalized with Covid-19, those who received hydroxychloroquine did not have a lower incidence of death at 28 days than those who received usual care. (Funded by UK Research and Innovation and National Institute for Health Research and others; RECOVERY ISRCTN number, ISRCTN50189673; ClinicalTrials.gov number, NCT04381936.).

Project description:BackgroundHydroxychloroquine has been widely administered to patients with Covid-19 without robust evidence supporting its use.MethodsWe examined the association between hydroxychloroquine use and intubation or death at a large medical center in New York City. Data were obtained regarding consecutive patients hospitalized with Covid-19, excluding those who were intubated, died, or discharged within 24 hours after presentation to the emergency department (study baseline). The primary end point was a composite of intubation or death in a time-to-event analysis. We compared outcomes in patients who received hydroxychloroquine with those in patients who did not, using a multivariable Cox model with inverse probability weighting according to the propensity score.ResultsOf 1446 consecutive patients, 70 patients were intubated, died, or discharged within 24 hours after presentation and were excluded from the analysis. Of the remaining 1376 patients, during a median follow-up of 22.5 days, 811 (58.9%) received hydroxychloroquine (600 mg twice on day 1, then 400 mg daily for a median of 5 days); 45.8% of the patients were treated within 24 hours after presentation to the emergency department, and 85.9% within 48 hours. Hydroxychloroquine-treated patients were more severely ill at baseline than those who did not receive hydroxychloroquine (median ratio of partial pressure of arterial oxygen to the fraction of inspired oxygen, 223 vs. 360). Overall, 346 patients (25.1%) had a primary end-point event (180 patients were intubated, of whom 66 subsequently died, and 166 died without intubation). In the main analysis, there was no significant association between hydroxychloroquine use and intubation or death (hazard ratio, 1.04, 95% confidence interval, 0.82 to 1.32). Results were similar in multiple sensitivity analyses.ConclusionsIn this observational study involving patients with Covid-19 who had been admitted to the hospital, hydroxychloroquine administration was not associated with either a greatly lowered or an increased risk of the composite end point of intubation or death. Randomized, controlled trials of hydroxychloroquine in patients with Covid-19 are needed. (Funded by the National Institutes of Health.).

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