Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

Chemoprophylaxis of SARS-CoV-2 Infection (COVID-19) in Exposed Healthcare Workers (COVIDAXIS)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04328285
Recruitment Status : Active, not recruiting
First Posted : March 31, 2020
Last Update Posted : June 1, 2020
Sponsor:
Collaborator:
Institut Pasteur
Information provided by (Responsible Party):
Centre Hospitalier Universitaire de Saint Etienne

Brief Summary:

Since December 2019, the emergence of a new coronavirus named SARS-Cov-2 in the city of Wuhan in China has been responsible for a major epidemic of respiratory infections, including severe pneumonia. Within weeks, COVID-19 became a pandemic.

In the absence of specific antiviral treatment, a special attention should be given to prevention. Personal protection equipments may be insufficiently protective, including in healthcare workers, a significant proportion of whom (around 4%) having been infected in the outbreaks described in China and more recently in Italy. Infection in healthcare workers could result from the contact with COVID-19 people in community or with infected colleagues or patients.

As it will take at least a year before vaccines against SARS-CoV-2 becomes available, chemoprophylaxis is an option that should be considered in this setting where prevention of SARS-CoV-2 infection in Health Care Workers.

The COVIDAXIS trial evaluates a chemoprophylaxis of SARS-CoV-2 infection in Health Care Workers. This trial is divided into two distinct studies that could start independently each with its own randomization process: COVIDAXIS 1 will study Hydroxychloroquine (HCQ) versus placebo; COVIDAXIS 2 will study Lopinavir/ritonavir (LPV/r) versus placebo.

Upon randomization healthcare workers (HCWs) involved in the management of suspected or confirmed COVID-19 cases will be assigned to one of the following 2 treatment groups:


Condition or disease Intervention/treatment Phase
COVID-19 Drug: Hydroxychloroquine Drug: Placebo of Hydroxychloroquine Drug: Lopinavir and ritonavir Drug: Placebo of LPV/r Tablets Phase 3

Detailed Description:

The study COVIDAXIS 1(Hydroxychloroquine (HCQ) versus placebo) will be realized on 600 participants and will be implemented first in as many centers as possible.

Upon randomization, with 1:1 allocation ratio, healthcare workers involved in the management of suspected or confirmed COVID-19 cases will be assigned to one of the following 2 treatment groups:

  • Group 1.1: HCQ 200 mg : 2 tablets on the evening at Day 1 and 2 tablets on the morning at Day 2 and 1 tablet once daily afterwards
  • Group 1.2: Placebo of HCQ, 2 tablets on the evening at Day 1 and 2 tablets on the morning at Day 2 and 1 tablet once daily afterwards.

The COVIDAXIS 2 (Lopinavir/ritonavir (LPV/r) versus placebo will be realized on 600 participants and will be implemented in already participating and newer centers in a second step (when LPV/r becomes available).

Upon randomization, with 1:1 allocation ratio, healthcare workers involved in the management of suspected or confirmed COVID-19 cases will be assigned to one of the following 2 treatment groups:

  • Group 2.1: LPV/r 200/50 mg : 2 tablets twice daily
  • Group 2.2: Placebo of LPV/r, 2 tablets twice daily

Participants will receive the randomized treatment for 2 months and will be followed upon a 2.5 months period.

NB: there is no randomization procedure for participant inclusion in either COVIDAXIS 1 or COVIDAXIS 2

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 1200 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: A randomized double-blind placebo-controlled clinical trial
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: Chemoprophylaxis of SARS-CoV-2 Infection (COVID-19) in Exposed Healthcare Workers : A Randomized Double-blind Placebo-controlled Clinical Trial
Actual Study Start Date : April 14, 2020
Estimated Primary Completion Date : November 30, 2020
Estimated Study Completion Date : November 30, 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Hydroxychloroquine (HCQ) vs Placebo

Group 1.1: HCQ 200 mg : 2 tablets on the evening at Day 1 and 2 tablets on the morning at Day 2 and 1 tablet once daily afterwards

Group 1.2: Placebo of HCQ, 2 tablets on the evening at Day 1 and 2 tablets on the morning at Day 2 and 1 tablet once daily afterwards.

Drug: Hydroxychloroquine
Hydroxychloroquine Oral Tablets
Other Name: Plaquenil

Drug: Placebo of Hydroxychloroquine
Placebo of Hydroxychloroquine Oral Tablets Placebo manufactured to mimic Hydroxychloroquine tablets

Experimental: Lopinavir/ritonavir (LPV/r) vs Placebo

Group 2.1: LPV/r 200/50 mg, 2 tablets twice daily

Group 2.2: Placebo of LPV/r, 2 tablets twice daily

Drug: Lopinavir and ritonavir
LPV/r Oral Tablets
Other Name: Kaletra

Drug: Placebo of LPV/r Tablets
Placebo of LPV/r Oral Tablets Placebo manufactured to mimic LPV/r tablets




Primary Outcome Measures :
  1. Occurrence of an symptomatic or asymptomatic SARS-CoV-2 infection among healthcare workers (HCWs) [ Time Frame: Up to 2.5 months ]

    An infection by SARS-CoV-2 is defined by either:

    • a positive specific Reverse Transcription - Polymerase Chain Reaction (RT-PCR) on periodic systematic nasopharyngeal swab during follow-up OR
    • a positive specific RT-PCR on a respiratory sample in case of onset of symptoms consistent with COVID-19 during follow-up OR
    • a seroconversion to SARS-CoV-2 after randomization.


Secondary Outcome Measures :
  1. Evaluation of the occurrence of adverse events in each arm, [ Time Frame: Up to 2.5 months ]
    Number of adverse events expected or unexpected, related and unrelated to the treatment, notably grades 2, 3 and 4 (moderate, severe and lifethreatening, according to the Adverse National Cancer Institute Common Terminology Criteria for Adverse Events, version 5.0) in each arm.

  2. Evaluation of the discontinuation rates of the investigational drug in each arm, [ Time Frame: Up to 2 months ]
    Number of treatment discontinuations in each arm

  3. Evaluation of the adherence of participants to study drug, [ Time Frame: Up to 2 months ]

    Treatment adherence rate will be assessed by:

    • measurement of LPV and HCQ plasma concentrations using LC-MS/MS or LC-Fluorimetric detection
    • the count of returned drugs at each visit.

  4. Evaluation of the incidence of symptomatic cases of SARS-CoV-2 infection in each arm, [ Time Frame: Up to 2.5 months ]

    Number of incident cases of symptomatic SARS-CoV-2 infections among HCWs in each arm.

    Symptomatic infection is defined as :

    • a positive specific RT-PCR on a respiratory or non respiratory sample OR
    • a thoracic CT scan with imaging abnormalities consistent with COVID-19.

    These investigations being performed in case of signs/symptoms consistent with COVID-19 during follow-up.


  5. Evaluation of the incidence of asymptomatic cases of SARS-CoV-2 infection in each arm [ Time Frame: Up to 2.5 months ]

    Number of incident cases of asymptomatic SARS-CoV-2 infection among HCWs in each randomization arm.

    Asymptomatic infection is defined as :

    • a positive specific RT-PCR on periodic systematic nasopharyngeal swab during clinical follow-up without consistent clinical signs/symptoms during follow-up OR
    • as seroconversion to SARS-CoV-2 between start and end of the study in HCWs that did not reported any consistent clinical symptoms during follow-up

  6. Evaluation of the incidence of severe cases of SARS-CoV-2 infection in each arm. [ Time Frame: Up to 2.5 months ]

    Number of incident cases of severe SARS-CoV-2 infections among HCWs in each randomization arm, defined as :

    • a positive specific RT-PCR on a respiratory sample OR
    • a thoracic CT scan with imaging abnormalities consistent with COVID-19 performed in case of onset of symptoms consistent with COVID-19 during follow-up in a participant who need to be hospitalized for respiratory distress. Respiratory distress defined as dyspnea with a respiratory frequency > 30/min, blood oxygen saturation <93%, partial pressure of arterial oxygen to fraction of inspired oxygen ratio <300 and/or lung infiltrates >50% (1).

  7. corrected QT interval (ms) [ Time Frame: At baseline, at D2 (only for COVIDAXIS 1) and every week up to 2 months. ]
    Safety. Electrocardiogram (ECG)



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Adult healthcare workers (HCWs) (physicians, nurses, assistant nurses, dentists, physiotherapists, and midwives)
  • HCW involved at the time of enrolment in the care of patients with confirmed or suspected SARS-CoV-2 infection in hospital settings, in outpatient care settings or in geriatric long-term care facilities
  • HCW tested negative for HIV
  • HCW affiliated to the French health insurance system
  • HCW women of childbearing age with an effective contraception (ethinylestradiol-containing contraceptive pills are not regarded as effective in the context of LPV/r treatment)
  • Willing to comply to study design and the follow-up
  • Consent form signed

Exclusion Criteria:

  • HCW with positive SARS-CoV-2 RT-PCR of nasopharyngeal swab at the inclusion visit.
  • HCW with past history of confirmed SARS-CoV-2 infection
  • HCW with positive SARS-CoV-2 serology at the inclusion visit (if the serology is available at inclusion time, if SARS-CoV-2 serology is not available, it will be a secondary exclusion criteria)
  • HCW with comorbidities such as chronic hepatitis C virus (HCV) infection treated by direct antiviral drugs or with hypothyroidism that need hormonal substitution, or retinopathy, or known to have hypercholesterolemia hypertriglyceridemia, or with prior intermittent porphyria, or chronic renal failure (glomerular filtration rate < 30mL/min) or prior hepatic failure or psoriasis.
  • HCW with prior diagnosis of glucose-6-phosphate dehydrogenase (G6PD) deficiency
  • HCW with known hypersensitivity/allergy to HCQ or LPV/r
  • HCW with baseline QTc interval > 450ms in men or > 460ms in women and QTc <320 ms (both gender)
  • HCW with personal or family history of long QT syndrome, torsades de pointes, or sudden death
  • Pregnant HCW
  • Breastfeeding HCW
  • HCW taking comedications known to have interactions with HCQ according to the official characteristics of the product

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04328285


Locations
Layout table for location information
France
CHU d'Angers
Angers, France
CHU de Bordeaux
Bordeaux, France, 33000
CHU de Clermont-Ferrand
Clermont-ferrand, France, 63000
CHU de Montpellier
Montpellier, France, 34000
CHU de Nancy
Nancy, France, 54000
CHU de Nantes
Nantes, France, 44000
AP-HP - Hôpital Bichat
Paris, France
CHU de Rennes
Rennes, France, 35000
CHU de Rouen
Rouen, France, 76000
CHU de Saint-Etienne
Saint-Étienne, France
Sponsors and Collaborators
Centre Hospitalier Universitaire de Saint Etienne
Institut Pasteur
Investigators
Layout table for investigator information
Principal Investigator: Elisabeth Botelho-Nevers, MD, PhD CHU de Saint-Etienne
Study Director: Bruno Hoen, MD, PhD Institut Pasteur
Layout table for additonal information
Responsible Party: Centre Hospitalier Universitaire de Saint Etienne
ClinicalTrials.gov Identifier: NCT04328285    
Other Study ID Numbers: 20PH061
2020-001188-96 ( EudraCT Number )
First Posted: March 31, 2020    Key Record Dates
Last Update Posted: June 1, 2020
Last Verified: May 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Centre Hospitalier Universitaire de Saint Etienne:
SARS-CoV-2
COVID-19
nasopharyngeal swab
pneumonia
Hydroxychloroquine
Lopinavir/ritonavir
Healthcare Workers
Additional relevant MeSH terms:
Layout table for MeSH terms
Infection
Ritonavir
Lopinavir
Hydroxychloroquine
HIV Protease Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Cytochrome P-450 CYP3A Inhibitors
Cytochrome P-450 Enzyme Inhibitors
Antimalarials
Antiprotozoal Agents
Antiparasitic Agents
Antirheumatic Agents