Hydroxychloroquine Post-Exposure Prophylaxis for Coronavirus Disease (COVID-19) Among Health-Care Workers

NCT04438837 | Unknown

• 1 other identifier: 0193-20-RMB CTIL
• Study Type: interventional
• Target: 582
• Locations: 1 country
• Sites: 1

Brief Summary

Background: The rapid spread and high infectivity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) makes identifying an effective prophylaxis agent highly important. One of the important target populations for such intervention who are at high risk of exposure are health care workers (HCWs) who may develop disease and/or expose patients and other HCWs. Hydroxychloroquine (HCQ), currently in usage for treatment of severe Coronavirus Disease 2019 (COVID-19), has in addition to in-vitro activities of inhibition of virus replication and immunomodulation, an important role in the inhibition of pre-entry step of the virus to host cells. Such activity in the early stage of infection may play a role in prevention of disease progression. Objectives: To evaluate the effect of HCQ in prevention of clinical disease and reduction of viral shedding among HCWs following exposure to confirmed COVID-19 patients. Study design: Multi-center, randomized controlled, superiority, open label trial Setting: The study will be conducted at Rambam Health Care Campus. Eligibility: Participants eligible for inclusion will include non-pregnant adult (\>18 years old) HCWs who were exposed to a confirmed case of COVID-19 without full adherence to droplet precautions. Participants will be eligible in a period no longer than 72 hours after exposure. Intervention: HCQ will be given in the intervention group in a dosage regimen of 400mg BID in the first day followed by 200mg BID for overall 10 days. Participants in the control group will receive no treatment. Treatment will be started no longer than 72 hours following exposure. Outcomes: The primary outcome will be the number of participants who develop clinical signs compatible with COVID 19 (defined in full protocol) within 14 days of exposure. Secondary outcomes will include virologically-confirmed COVID 19, disease severity (need for hospitalization, mechanical ventilation and 30-day mortality) and viral shedding duration (time between first positive PCR to last of two consecutive negative tests) for confirmed COVID 19 cases. Sample size: The trial will test for HCQ's superiority assuming a primary outcome incidence of 20% in the control group and a reduction of 50% with HCQ. The sample size required for a power of 80% (alpha 0.05) is 291 participants per each group.

Conditions

Coronavirus Disease 2019 (COVID-19); Post-Exposure Prophylaxis

Keywords

COVID-19; severe acute respiratory syndrome coronavirus 2; Hydroxychloroquine; Post-Exposure Prophylaxis

Outcome Measures

Primary Outcomes (1)

• Clinical COVID-19

  Number of patients developing clinical symptoms and signs compatible with COVID-19 following exposure

  14 days following exposure.

Secondary Outcomes (9)

• Confirmed COVID-19

  14 days following exposure.

• Time to virological recovery

  30 days

• Time to symptoms onset

  14 days

• Development of pneumonia

  14 days

• Development of severe disease

  14 days

Study Arms (2)

control group

NO INTERVENTION

no intervention

intervention group

ACTIVE COMPARATOR

participants will recieve hydroxychloroquine in a dosage regimen of 400mg BID in the first day followed by 200mg BID for overall 10 days.

Drug: Hydroxychloroquine

Interventions

Hydroxychloroquine DRUG

Hydroxychloroquine post exposure prohylaxis

Also known as: Plaquenil

intervention group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adult participant (\>18 years)
• HCW who had a contact without adequate personal protective equipment (PPE) with a confirmed COVID-19 patient.
• Time between exposure to randomization no longer than 72 hours.
• Informed consent from participant

You may not qualify if:

• Symptoms compatible with COVID-19 upon randomization
• Known allergy to HCQ or chloroquine
• History of any arrhythmia.
• Severely reduced LV function (Ejection fraction\<30%)
• Retinopathy
• Pregnancy or breast feeding
• Concomitant treatment with azithromycin, flecainide, amiodarone, digoxin, procainamide, propafenone, thioridazine, pimozide.
• Chronic chloroquine/ HCQ treatment

Sponsors & Collaborators

• Rambam Health Care Campus: lead

Study Sites (1)

Rambam Health Care Campus

Haifa, Israel

Location

Related Publications (6)

• Wu Z, McGoogan JM. Characteristics of and Important Lessons From the Coronavirus Disease 2019 (COVID-19) Outbreak in China: Summary of a Report of 72 314 Cases From the Chinese Center for Disease Control and Prevention. JAMA. 2020 Apr 7;323(13):1239-1242. doi: 10.1001/jama.2020.2648. No abstract available.

  PMID: 32091533 RESULT

• Livingston E, Bucher K. Coronavirus Disease 2019 (COVID-19) in Italy. JAMA. 2020 Apr 14;323(14):1335. doi: 10.1001/jama.2020.4344. No abstract available.

  PMID: 32181795 RESULT

• Chan JF, Yuan S, Kok KH, To KK, Chu H, Yang J, Xing F, Liu J, Yip CC, Poon RW, Tsoi HW, Lo SK, Chan KH, Poon VK, Chan WM, Ip JD, Cai JP, Cheng VC, Chen H, Hui CK, Yuen KY. A familial cluster of pneumonia associated with the 2019 novel coronavirus indicating person-to-person transmission: a study of a family cluster. Lancet. 2020 Feb 15;395(10223):514-523. doi: 10.1016/S0140-6736(20)30154-9. Epub 2020 Jan 24.

  PMID: 31986261 RESULT

• Chang D, Xu H, Rebaza A, Sharma L, Dela Cruz CS. Protecting health-care workers from subclinical coronavirus infection. Lancet Respir Med. 2020 Mar;8(3):e13. doi: 10.1016/S2213-2600(20)30066-7. Epub 2020 Feb 13. No abstract available.

  PMID: 32061333 RESULT

• Shiryaev SA, Mesci P, Pinto A, Fernandes I, Sheets N, Shresta S, Farhy C, Huang CT, Strongin AY, Muotri AR, Terskikh AV. Repurposing of the anti-malaria drug chloroquine for Zika Virus treatment and prophylaxis. Sci Rep. 2017 Nov 17;7(1):15771. doi: 10.1038/s41598-017-15467-6.

  PMID: 29150641 RESULT

• Devaux CA, Rolain JM, Colson P, Raoult D. New insights on the antiviral effects of chloroquine against coronavirus: what to expect for COVID-19? Int J Antimicrob Agents. 2020 May;55(5):105938. doi: 10.1016/j.ijantimicag.2020.105938. Epub 2020 Mar 12.

  PMID: 32171740 RESULT

Related Links

• coronaviruse/situation-reports

MeSH Terms

Conditions

COVID-19

Interventions

Hydroxychloroquine

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Chloroquine; Aminoquinolines; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Mical Paul, MD

  Rambam

  STUDY CHAIR

Central Study Contacts

Nesrin Ghanem-Zoubi, MD

CONTACT

97247772991; n_ghanem@rambam.health.gov.il

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Infectious Diseases Institute senior physician

Study Record Dates

• First Submitted: June 18, 2020
• First Posted: June 19, 2020
• Study Start: July 1, 2020
• Primary Completion: June 1, 2022
• Study Completion: June 1, 2022
• Last Updated: July 23, 2020

Record last verified: 2020-07

Locations

IL (1)