Working…
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 : December 28, 2020
Sponsor:
Collaborator:
Institut Pasteur
Information provided by (Responsible Party):
Centre Hospitalier Universitaire de Saint Etienne

Tracking Information
First Submitted Date  ICMJE March 25, 2020
First Posted Date  ICMJE March 31, 2020
Last Update Posted Date December 28, 2020
Actual Study Start Date  ICMJE April 14, 2020
Estimated Primary Completion Date March 30, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 27, 2020)
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.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: April 8, 2020)
  • 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.
  • 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
  • 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.
  • 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.
  • 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
  • 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).
  • corrected QT interval (ms) [ Time Frame: At baseline, at D2 (only for COVIDAXIS 1) and every week up to 2 months. ]
    Safety. Electrocardiogram (ECG)
Original Secondary Outcome Measures  ICMJE
 (submitted: March 27, 2020)
  • 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.
  • 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
  • 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.
  • 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.
  • 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
  • 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).
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Chemoprophylaxis of SARS-CoV-2 Infection (COVID-19) in Exposed Healthcare Workers
Official Title  ICMJE Chemoprophylaxis of SARS-CoV-2 Infection (COVID-19) in Exposed Healthcare Workers : A Randomized Double-blind Placebo-controlled Clinical Trial
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:

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

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE 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
Condition  ICMJE COVID-19
Intervention  ICMJE
  • Drug: Hydroxychloroquine
    Hydroxychloroquine Oral Tablets
    Other Name: Plaquenil
  • Drug: Placebo of Hydroxychloroquine
    Placebo of Hydroxychloroquine Oral Tablets Placebo manufactured to mimic Hydroxychloroquine tablets
  • 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
Study Arms  ICMJE
  • 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.

    Interventions:
    • Drug: Hydroxychloroquine
    • Drug: Placebo of Hydroxychloroquine
  • 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

    Interventions:
    • Drug: Lopinavir and ritonavir
    • Drug: Placebo of LPV/r Tablets
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Estimated Enrollment  ICMJE
 (submitted: March 27, 2020)
1200
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE March 30, 2021
Estimated Primary Completion Date March 30, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Adult healthcare workers (HCWs) (for instance physicians, nurses, assistant nurses, dentists, physiotherapists, midwives, etc.)
  • HCW involved at the time of enrolment in the care and the management of patients with confirmed or suspected SARS-CoV-2 infection in hospital settings, in outpatient care settings or in geriatric long-term care facilities. These HCWs have prolonged or repeated close contact to these patients.
  • 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 - COVIDAXIS 2)
  • Willing to comply to study design and the follow-up
  • Consent form signed

Exclusion Criteria:

For COVIDAXIS 1:

  • 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
  • HCW with comorbidities such as hypothyroidism that need hormonal substitution, or retinopathy 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
  • 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

For COVIDAXIS 2:

  • 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
  • HCW with comorbidities such as chronic HCV infection treated by direct antiviral drugs or with hypothyroidism that need hormonal substitution, or known to have hypercholesterolemia hypertriglyceridemiaor chronic renal failure (glomerular filtration rate < 30mL/min) or prior hepatic failure
  • HCW with known hypersensitivity/allergy to 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 LPV/r according to the official characteristics of the product
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE France
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04328285
Other Study ID Numbers  ICMJE 20PH061
2020-001188-96 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Centre Hospitalier Universitaire de Saint Etienne
Study Sponsor  ICMJE Centre Hospitalier Universitaire de Saint Etienne
Collaborators  ICMJE Institut Pasteur
Investigators  ICMJE
Principal Investigator: Elisabeth Botelho-Nevers, MD, PhD CHU de Saint-Etienne
Study Director: Bruno Hoen, MD, PhD Institut Pasteur
PRS Account Centre Hospitalier Universitaire de Saint Etienne
Verification Date December 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP