Hydroxychloroquine as a therapeutic

Background

Hydroxychloroquine has been widely promoted as a potential therapy

Anti-inflammatory, reduced production of pro-inflammatory cytokines

Antiviral activity

Ionophore for zinc

Invitro reduced viral entry into cells

Adopted into routine care for hospitalized adults with COVID-19

UK recovery trial, (5th June, 2020)

)304604/fulltext

11,000 patients from 175 NHS hospitals in the UK

No clinical benefit from use of hydroxychloroquine in hospitalised patients with COVID-19

WHO Solidarity trial

December 2019 to April 2020, 96,000 patients

Showed an increased risk of dying in hospital and de novo ventricular arrhythmia

800 mg BD for one day

then

400 mg BD for 10 days

Total of 22 doses

Previous video on Hydroxychloroquine

Does Hydroxychloroquine work (10th May, 2020)

Hydroxychloroquine, Studies (27th May, 2020)

Hydroxychloroquine, evidence of efficacy (27th August 2020)

Pandemic Science, Reinfections and hydroxychloroquine (28th August, 2020)

Effect of Hydroxychloroquine on Clinical Status at 14 Days in Hospitalized Patients With COVID-19

JAMA, 9th November

Multicenter, blinded, placebo-controlled randomized trial

Conducted at 34 hospitals in the US

Adults hospitalized with respiratory symptoms

Severe acute respiratory syndrome

April 2 and June 19, 2020

Trial was stopped at the fourth interim analysis for futility with a sample size of 479 patients

Interventions group, n = 242

Hydroxychloroquine

400 mg twice daily for 2 doses

then 200 mg twice daily for 8 doses

A total of 10 doses over 5 days

Placebo group n = 237

Given placebo meds

Outcomes and Measures

The primary outcome was clinical status 14 days after randomization

Assessed with a 7-category ordinal scale

Ranging from 1 (death) to 7 (discharged able to do normal duties)

1, death

2, hospitalized, receiving extracorporeal membrane oxygenation (ECMO) or invasive mechanical ventilation

3, hospitalized, receiving noninvasive mechanical ventilation or nasal high-flow oxygen therapy

4, hospitalized, receiving supplemental oxygen without positive pressure or high flow

5, hospitalized, not receiving supplemental oxygen

6, not hospitalized and unable to perform normal activities

7, not hospitalized and able to perform normal activities

Also 12 secondary outcomes, including 28-day mortality.

Participants

Female, 44.3%

Hispanic/Latinx, 23.4%

Black, 20.1%

Receiving supplemental oxygen, 46.8%

Oxygen with pressure,11.5%

Invasive mechanical ventilation, 6.7%

Median duration of symptoms prior to randomization was 5 days

Result

Clinical status on the ordinal outcome scale at 14 days did not significantly differ between the hydroxychloroquine and placebo groups

aOR, 1.02

None of the 12 secondary outcomes were significantly different between groups

At 28 days after randomization

Hydroxychloroquine group

25 of 241 patients (10.4%) had died

Placebo group

25 of 236 (10.6%) had died

aOR, 1.07

Conclusions and Relevance

Among adults hospitalized with respiratory illness from COVID-19

Hydroxychloroquine, did not significantly improve clinical status at day 14 or reduce deaths at 28 days

These findings do not support the use of hydroxychloroquine for treatment of COVID-19 among hospitalized adults.