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

NCT04328285 | Terminated Phase 3 DMC

• 2 other identifiers: 20PH0612020-001188-96
• Study Type: interventional
• Target: 118
• Locations: 1 country
• Sites: 9

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:

Conditions

COVID-19

Keywords

SARS-CoV-2; COVID-19; nasopharyngeal swab; pneumonia; Hydroxychloroquine; Lopinavir/ritonavir; Healthcare Workers

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (7)

• Evaluation of the occurrence of adverse events in each arm,

  Up to 2.5 months

• Evaluation of the discontinuation rates of the investigational drug in each arm,

  Up to 2 months

• Evaluation of the adherence of participants to study drug,

  Up to 2 months

• Evaluation of the incidence of symptomatic cases of SARS-CoV-2 infection in each arm,

  Up to 2.5 months

• Evaluation of the incidence of asymptomatic cases of SARS-CoV-2 infection in each arm

  Up to 2.5 months

Study Arms (2)

Hydroxychloroquine (HCQ) vs Placebo

EXPERIMENTAL

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; Drug: Placebo of Hydroxychloroquine

Lopinavir/ritonavir (LPV/r) vs Placebo

EXPERIMENTAL

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; Drug: Placebo of LPV/r Tablets

Interventions

Hydroxychloroquine DRUG

Hydroxychloroquine Oral Tablets

Also known as: Plaquenil

Hydroxychloroquine (HCQ) vs Placebo

Placebo of Hydroxychloroquine DRUG

Placebo of Hydroxychloroquine Oral Tablets Placebo manufactured to mimic Hydroxychloroquine tablets

Hydroxychloroquine (HCQ) vs Placebo

Lopinavir and ritonavir DRUG

LPV/r Oral Tablets

Also known as: Kaletra

Lopinavir/ritonavir (LPV/r) vs Placebo

Placebo of LPV/r Tablets DRUG

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

Lopinavir/ritonavir (LPV/r) vs Placebo

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• For COVIDAXIS 1:
• HCW with past history of confirmed SARS-CoV-2 infection
• 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 past history of confirmed SARS-CoV-2 infection
• 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)

Sponsors & Collaborators

• Centre Hospitalier Universitaire de Saint Etienne: lead
• Institut Pasteur: collaborator

Study Sites (9)

CHU d'Angers

Angers, France

Location

CHU de Bordeaux

Bordeaux, 33000, France

Location

CHU de Clermont-Ferrand

Clermont-Ferrand, 63000, France

Location

CHU de Montpellier

Montpellier, 34000, France

Location

CHU de Nancy

Nancy, 54000, France

Location

CHU de Nantes

Nantes, 44000, France

Location

CHU de Rennes

Rennes, 35000, France

Location

CHU de Rouen

Rouen, 76000, France

Location

CHU de Saint-Etienne

Saint-Etienne, France

Location

MeSH Terms

Conditions

COVID-19; Pneumonia

Interventions

Hydroxychloroquine; lopinavir-ritonavir drug combination

Condition Hierarchy (Ancestors)

Pneumonia, Viral; 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

• Elisabeth Botelho-Nevers, MD, PhD

  CHU de Saint-Etienne

  PRINCIPAL INVESTIGATOR

• Bruno Hoen, MD, PhD

  Institut Pasteur

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: A randomized double-blind placebo-controlled clinical trial

Study Record Dates

• First Submitted: March 25, 2020
• First Posted: March 31, 2020
• Study Start: April 14, 2020
• Primary Completion: May 13, 2020
• Study Completion: March 30, 2022
• Last Updated: March 1, 2023

Record last verified: 2023-02

Data Sharing

• IPD Sharing: Will not share

Locations

FR (9)