Back >>

Can hydroxychloroquine be used as post-exposure prophylaxis for COVID-19 patients who have been exposed as healthcare workers, in a household setting, or other occupational settings?

Comment by InpharmD Researcher

There appears to be no benefit to using hydroxychloroquine as post-exposure prophylaxis for COVID-19 patients who have been exposed as a healthcare worker, in a household setting, or in another occupational setting.
Background

The National Institute of Health guidelines recommend against the use of chloroquine or hydroxychloroquine for the treatment of coronavirus (COVID)-19, except in the setting of a clinical trial. No agent given before or after an exposure to COVID-19 is known to be effective in preventing the infection. Agents for pre or post-exposure prophylaxis are only advised in the setting of a clinical trial.[1]

The Food and Drug Administration has not approved any drugs for the treatment of COVID-19, and has revoked the emergency use authorization of chloroquine and hydroxychloroquine. [2]

Current clinical management includes infection prevention and control measures and supportive care, including supplemental oxygen and mechanical ventilatory support when indicated. [3]

Infectious Diseases Society of America (IDSA) guidelines recommend that hydroxychloroquine be used in COVID-19 patients only in the context of a clinical trial. [4]

Hydroxychloroquine is recommended to be used for COVID-19 in the context of a carefully constructed randomized clinical trial, with a strong focus on the costs and benefits involved. [5]

A meta-analyses of 26 studies looked at clinical or observational trials exploring the effects of hydroxychloroquine treatment for COVID-19 patients. The meta-analyses demonstrated that there was no clinical benefit seen with hydroxychloroquine with or without azithromycin for COVID-19 patients. [6]

References:

[1] COVID-19 Treatment Guidelines Panel. Coronavirus Disease 2019 (COVID-19) Treatment Guidelines. National Institutes of
Health. Available at https://www.covid19treatmentguidelines.nih.gov/. Accessed [June 23, 2020].

[2]Commissioner, Office of the. “Coronavirus (COVID-19) Update: FDA Revokes Emergency Use Authorization for Chloroquine and Hydroxychloroquine.” U.S. Food and Drug Administration, FDA, www.fda.gov/news-events/press-announcements/coronavirus-covid-19-update-fda-revokes-emergency-use-authorization-chloroquine-and.

[3] “Therapeutic Options for COVID-19 Patients.” Centers for Disease Control and Prevention, Centers for Disease Control and Prevention, 25 Apr. 2020, www.cdc.gov/coronavirus/2019-ncov/hcp/therapeutic-options.html.

[4] Bhimraj, Adarsh, et al. “Infectious Diseases Society of America Guidelines on the Treatment and Management of Patients with COVID-19.” Clinical Infectious Diseases, 2020, doi:10.1093/cid/ciaa478.

[5] Meyerowitz, Eric A., et al. “Rethinking the Role of Hydroxychloroquine in the Treatment of COVID‐19.” The FASEB Journal, vol. 34, no. 5, 2020, pp. 6027–6037., doi:10.1096/fj.202000919.

[6] “Hydroxychloroquine Versus COVID-19: A Rapid Systematic Review and Meta-Analysis.” doi:10.37473/dac/10.1101/2020.04.14.20065276.

Relevant Prescribing Information

Hydroxychloroquine is an agent with anti-inflammatory and immunomodulatory effects. It is used to treat illnesses such as; Malaria, Lupus Erythematosus, and Rheumatoid Arthritis. It should be contraindicated in patients with known hypersensitivity to 4-aminoquinoline compounds.[1]

Associated warnings include ocular damage, cardiomyopathy and QT prolongation, worsening of psoriasis and porphyria, proximal myopathy and neuropathy, neuropsychiatric events including suicidal ideation, and hypoglycemia.[1]

This drug should be used with caution in patients with gastrointestinal, neurological, or blood disorders, and in those with a sensitivity to quinine.[1]

References:

[1] Hydroxychloroquine Sulfate Tablets, USP [package insert], St.Michael, Barbados: Concordia Pharmaceuticals Inc. accessFDA.gov

Literature Review

A search of the published medical literature revealed 1 study investigating the researchable question:

Can hydroxychloroquine be used as post-exposure prophylaxis for COVID-19 patients who have been exposed as healthcare workers, in a household setting, or other occupational settings?

Please see Table 1 for your response.


A Randomized Trial of Hydroxychloroquine as Post-Exposure Prophylaxis for COVID-19

Design

Randomized, double-blind, placebo-controlled trial

N= 821

Objective

To determine whether hydroxychloroquine could be used as postexposure prophylaxis to prevent symptomatic infection after exposure to COVID-19

Methods

Asymptomatic adults who had household or occupational exposure to someone with confirmed COVID-19 at a distance of less than six feet for more than ten minutes while wearing neither a face mask nor an eye shield (high-risk exposure), or while wearing a face mask but no eye shield (moderate-risk exposure), were enrolled in the study.

Within four days of exposure participants were randomized to receive placebo or hydroxychloroquine 800 mg once, followed by 600 mg in six to eight hours, then 600 mg daily for four additional days.

 The incidence of laboratory-confirmed COVID-19 or illness compatible with COVID-19 was assessed within 14 days.

Study Groups/Patients

 

Exposure

Type:

Patients:

Household contact

245

As a healthcare worker

545

Other occupational exposure

31

 

 

Study Groups:

Patients:

Hydroxychloroquine

414

Placebo

407

 

   

Outcome Measures

The primary outcome was symptomatic illness confirmed by a positive molecular assay or, if testing was unavailable, COVID-19-related symptoms (presence of cough, shortness of breath, difficulty breathing; or the combination of two of the following: fever, chills, rigors, myalgia, headache, sore throat, and olfactory or taste disorders).

 

 

Results

Overall, new COVID-19 developed in 107 of 821 participants (13.0%) during the 14 days of follow-up.

 

The incidence of new illness compatible with COVID-19 was seen in 49 patients receiving hydroxychloroquine (11.8%) and in 58 patients receiving placebo (14.3%), with a P-value of 0.35.

 

 

Outcomes of Hydroxychloroquine Therapy for Postexposure Prophylaxis against COVID-19

 

Shown in number (percent)

 

Outcome

Hydroxychloroquine

Placebo

P-value

Confirmed or probable COVID-19

49 (11.8)

58 (14.3)

0.35

Laboratory-confirmed diagnosis

11 (2.7)

9 (2.2)

0.82

Symptoms compatible with COVID-19

48 (11.6)

55 (13.5)

0.46

All new symptoms

57 (13.8)

59 (14.5)

0.84

Any hospitalizations

1 (0.2)

1 (0.2)

0.99

Deaths

0

0

––

Study Author Conclusions

No significant benefit of hydroxychloroquine as post-exposure prophylaxis for COVID-19 was demonstrated in this trial.

 

InpharmD Researcher Critique

While this study had a large sample size, the availability of testing was not standard amongst patient groups. Furthermore, evaluation of different COVID-19 symptoms and diagnoses was not uniform. No benefit was seen when using hydroxychloroquine for post- exposure prophylaxis.