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

Primary Purpose

COVID-19

Status
Terminated
Phase
Phase 3
Locations
France
Study Type
Interventional
Intervention
Hydroxychloroquine
Placebo of Hydroxychloroquine
Lopinavir and ritonavir
Placebo of LPV/r Tablets
Sponsored by
Centre Hospitalier Universitaire de Saint Etienne
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for COVID-19 focused on measuring SARS-CoV-2, COVID-19, nasopharyngeal swab, pneumonia, Hydroxychloroquine, Lopinavir/ritonavir, Healthcare Workers

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesAccepts Healthy Volunteers

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

Sites / Locations

  • CHU d'Angers
  • CHU de Bordeaux
  • CHU de Clermont-Ferrand
  • CHU de Montpellier
  • CHU de Nancy
  • CHU de Nantes
  • CHU de Rennes
  • CHU de Rouen
  • CHU de Saint-Etienne

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Hydroxychloroquine (HCQ) vs Placebo

Lopinavir/ritonavir (LPV/r) vs Placebo

Arm Description

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.

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

Outcomes

Primary Outcome Measures

Occurrence of an symptomatic or asymptomatic SARS-CoV-2 infection among healthcare workers (HCWs)
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

Evaluation of the occurrence of adverse events in each arm,
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,
Number of treatment discontinuations in each arm
Evaluation of the adherence of participants to study drug,
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,
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
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.
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)
Safety. Electrocardiogram (ECG)

Full Information

First Posted
March 25, 2020
Last Updated
February 28, 2023
Sponsor
Centre Hospitalier Universitaire de Saint Etienne
Collaborators
Institut Pasteur
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1. Study Identification

Unique Protocol Identification Number
NCT04328285
Brief Title
Chemoprophylaxis of SARS-CoV-2 Infection (COVID-19) in Exposed Healthcare Workers
Acronym
COVIDAXIS
Official Title
Chemoprophylaxis of SARS-CoV-2 Infection (COVID-19) in Exposed Healthcare Workers : A Randomized Double-blind Placebo-controlled Clinical Trial
Study Type
Interventional

2. Study Status

Record Verification Date
February 2023
Overall Recruitment Status
Terminated
Why Stopped
French authority's decision
Study Start Date
April 14, 2020 (Actual)
Primary Completion Date
May 13, 2020 (Actual)
Study Completion Date
March 30, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Centre Hospitalier Universitaire de Saint Etienne
Collaborators
Institut Pasteur

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
COVID-19
Keywords
SARS-CoV-2, COVID-19, nasopharyngeal swab, pneumonia, Hydroxychloroquine, Lopinavir/ritonavir, Healthcare Workers

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Model Description
A randomized double-blind placebo-controlled clinical trial
Masking
ParticipantInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
118 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Hydroxychloroquine (HCQ) vs Placebo
Arm Type
Experimental
Arm Description
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.
Arm Title
Lopinavir/ritonavir (LPV/r) vs Placebo
Arm Type
Experimental
Arm Description
Group 2.1: LPV/r 200/50 mg, 2 tablets twice daily Group 2.2: Placebo of LPV/r, 2 tablets twice daily
Intervention Type
Drug
Intervention Name(s)
Hydroxychloroquine
Other Intervention Name(s)
Plaquenil
Intervention Description
Hydroxychloroquine Oral Tablets
Intervention Type
Drug
Intervention Name(s)
Placebo of Hydroxychloroquine
Intervention Description
Placebo of Hydroxychloroquine Oral Tablets Placebo manufactured to mimic Hydroxychloroquine tablets
Intervention Type
Drug
Intervention Name(s)
Lopinavir and ritonavir
Other Intervention Name(s)
Kaletra
Intervention Description
LPV/r Oral Tablets
Intervention Type
Drug
Intervention Name(s)
Placebo of LPV/r Tablets
Intervention Description
Placebo of LPV/r Oral Tablets Placebo manufactured to mimic LPV/r tablets
Primary Outcome Measure Information:
Title
Occurrence of an symptomatic or asymptomatic SARS-CoV-2 infection among healthcare workers (HCWs)
Description
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.
Time Frame
Up to 2.5 months
Secondary Outcome Measure Information:
Title
Evaluation of the occurrence of adverse events in each arm,
Description
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.
Time Frame
Up to 2.5 months
Title
Evaluation of the discontinuation rates of the investigational drug in each arm,
Description
Number of treatment discontinuations in each arm
Time Frame
Up to 2 months
Title
Evaluation of the adherence of participants to study drug,
Description
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.
Time Frame
Up to 2 months
Title
Evaluation of the incidence of symptomatic cases of SARS-CoV-2 infection in each arm,
Description
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.
Time Frame
Up to 2.5 months
Title
Evaluation of the incidence of asymptomatic cases of SARS-CoV-2 infection in each arm
Description
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
Time Frame
Up to 2.5 months
Title
Evaluation of the incidence of severe cases of SARS-CoV-2 infection in each arm.
Description
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).
Time Frame
Up to 2.5 months
Title
corrected QT interval (ms)
Description
Safety. Electrocardiogram (ECG)
Time Frame
At baseline, at D2 (only for COVIDAXIS 1) and every week up to 2 months.

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Elisabeth Botelho-Nevers, MD, PhD
Organizational Affiliation
CHU de Saint-Etienne
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Bruno Hoen, MD, PhD
Organizational Affiliation
Institut Pasteur
Official's Role
Study Director
Facility Information:
Facility Name
CHU d'Angers
City
Angers
Country
France
Facility Name
CHU de Bordeaux
City
Bordeaux
ZIP/Postal Code
33000
Country
France
Facility Name
CHU de Clermont-Ferrand
City
Clermont-ferrand
ZIP/Postal Code
63000
Country
France
Facility Name
CHU de Montpellier
City
Montpellier
ZIP/Postal Code
34000
Country
France
Facility Name
CHU de Nancy
City
Nancy
ZIP/Postal Code
54000
Country
France
Facility Name
CHU de Nantes
City
Nantes
ZIP/Postal Code
44000
Country
France
Facility Name
CHU de Rennes
City
Rennes
ZIP/Postal Code
35000
Country
France
Facility Name
CHU de Rouen
City
Rouen
ZIP/Postal Code
76000
Country
France
Facility Name
CHU de Saint-Etienne
City
Saint-Étienne
Country
France

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

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

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