Hydroxychloroquine, evidence of efficacy

Belgium, not Dutch. Low-dose Hydroxychloroquine Therapy and Mortality in Hospitalized Patients with COVID-19: A Nationwide Observational Study of 8075 Participants (International Journal of Antimicrobial Agents, 24 August)

Background

Hydroxychloroquine (HCQ) has been largely used and investigated as therapy of COVID-19 , at total dose usually ranging from 2400 mg to 9600 mg.

In Belgium, off-label use of low-dose HCQ (2400 mg in total over five days) was recommended for hospitalized patients with COVID-19.

“low-dose” regimen of HCQ sulphate in monotherapy

400mg twice on day 1

200mg twice a day from day 2 to 5

i.e. a total dose of 2400 mg

Methods

Multi-centric design

Vast majority of Belgian hospitals

Retrospective analysis

In-hospital mortality in Belgium

40 day follow up

No difference in the baseline characteristics

Groups

HCQ alone and supportive care

Supportive care only

Adjusted for demographic and clinical features

Results

8075 patients with complete discharge data

HCQ group, n = 4,542

Deaths, 804, (17.7%)

no-HCQ group, n = 3,533

Deaths, 957 (27.1%)

Multivariable analysis

Mortality was lower in the HCQ group compared to the no-HCQ group

Hazard ratio = 0.684

Estimated direct-adjusted mortality at 40 days

19.1% with HCQ alone

26.5% with supportive care only

Mortality in the HCQ group was reduced

Both in patients diagnosed in less than 5 days and more than 5 days

Conclusions

Compared to supportive care only, low-dose HCQ monotherapy was independently associated with lower mortality in hospitalized patients with COVID-19 diagnosed and treated early or later after symptom onset.

Other positive studies

Risk Factors for Mortality in Patients with COVID-19 in New York City

Hydroxychloroquine use was associated with decreased in-hospital mortality

Treatment with hydroxychloroquine, azithromycin, and combination in patients hospitalized with COVID-19

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treatment with hydroxychloroquine alone and in combination with azithromycin was associated with reduction in COVID-19 associated mortality

Recovery Trial

Effect of Hydroxychloroquine in Hospitalized Patients with COVID-19: Preliminary results from a multi-centre, randomized, controlled trial. 15 July 2020

Hydroxychloroquine group, n = 1,561

Usual care group, n = 3,155

Patients allocated to hydroxychloroquine sulfate (200mg) received a loading dose of 4 tablets (800 mg) at zero and 6 hours, followed by 2 tablets (400 mg) starting at 12 hours after the initial dose and then every 12 hours for the next 9 days

9,200 mg over 10 days

Conclusion

In patients hospitalized with COVID-19, hydroxychloroquine was not associated with reductions in 28-day mortality

Was associated with an increased length of hospital stay and increased risk of progressing to invasive mechanical ventilation or death

WHO-led SOLIDARITY

9600 mg over 10 days

Provided no benefit in hospitalized patients with COVID-19

Hydroxychloroquine with or without Azithromycin in Mild-to-Moderate Covid-19 (NEJM23 July) Brazil

METHODS

55 hospitals, Brazil

Randomized

Open label

Three-group

Controlled

Patients

667 patients, 504 confirmed Covid-19

Receiving no supplemental oxygen

Or a maximum of 4 liters per minute

1:1:1

Standard care n = 229

Standard care plus hydroxychloroquine (400 mg twice daily) n = 221

Standard care plus hydroxychloroquine (400 mg twice daily) plus azithromycin (500 mg once

daily for 7 days) n = 277

RESULTS

No difference in need for ventilation, deaths, thromboembolic complications, AKI

Clinical status at 15 days

As compared with standard care = 1

Hydroxychloroquine alone, odds ratio, 1.21

Hydroxychloroquine plus azithromycin, odds ratio, 0.99

HCQ Group

Prolongation of the corrected QT interval and

Elevation of liver-enzyme levels

CONCLUSIONS

Among patients hospitalized with mild-to-moderate Covid-19, the use of hydroxychloroquine, alone or with azithromycin, did not improve clinical status at 15 days as compared with standard care.