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

COVID-19 Clinical Trial

— COVIDAXIS  

Official title:

Chemoprophylaxis of SARS-CoV-2 Infection (COVID-19) in Exposed Healthcare Workers : A Randomized Double-blind Placebo-controlled Clinical Trial

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT04328285
• Other study ID #: 20PH061
• Secondary ID: 2020-001188-96
• Status: Terminated
• Phase: Phase 3
• Start date: April 14, 2020
• Est. completion date: March 30, 2022

Study information

• Verified date: February 2023
• Source: Centre Hospitalier Universitaire de Saint Etienne
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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:

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

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 118
• Est. completion date: March 30, 2022
• Est. primary completion date: May 13, 2020
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• COVID-19

Intervention

Drug:
• Hydroxychloroquine
Hydroxychloroquine Oral Tablets
• Placebo of Hydroxychloroquine
Placebo of Hydroxychloroquine Oral Tablets Placebo manufactured to mimic Hydroxychloroquine tablets
• Lopinavir and ritonavir
LPV/r Oral Tablets
• Placebo of LPV/r Tablets
Placebo of LPV/r Oral Tablets Placebo manufactured to mimic LPV/r tablets

Locations

Country	Name	City	State
France	CHU d'Angers	Angers
France	CHU de Bordeaux	Bordeaux
France	CHU de Clermont-Ferrand	Clermont-ferrand
France	CHU de Montpellier	Montpellier
France	CHU de Nancy	Nancy
France	CHU de Nantes	Nantes
France	CHU de Rennes	Rennes
France	CHU de Rouen	Rouen
France	CHU de Saint-Etienne	Saint-Étienne

Sponsors (2)

Lead Sponsor	Collaborator
Centre Hospitalier Universitaire de Saint Etienne	Institut Pasteur

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Up to 2.5 months
Secondary	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.	Up to 2.5 months
Secondary	Evaluation of the discontinuation rates of the investigational drug in each arm,	Number of treatment discontinuations in each arm	Up to 2 months
Secondary	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.	Up to 2 months
Secondary	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.	Up to 2.5 months
Secondary	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	Up to 2.5 months
Secondary	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).	Up to 2.5 months
Secondary	corrected QT interval (ms)	Safety. Electrocardiogram (ECG)	At baseline, at D2 (only for COVIDAXIS 1) and every week up to 2 months.