Chemoprophylaxis of SARS-CoV-2 infection (COVID-19) in exposed healthcare workers: a randomized double-blind placebo-controlled clinical trial

Chemoprophylaxis of SARS-CoV-2 infection (COVID-19) in exposed healthcare workers: a randomized double-blind placebo-controlled clinical trial - COVIDAXIS

Status

Not yet recruiting

Phases

Phase 3

Study type

Interventional

Source

EU CTR

Registry ID

EUCTR2020-001188-96-FR

Enrollment

1200

Registered

2020-03-24

Start date

2020-04-07

Completion date

Unknown

Last updated

2020-04-14

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Healthcare workers MedDRA version: 21.1 Level: LLT Classification code 10008434 Term: Chemoprophylaxis NOS System Organ Class: 100000004865 MedDRA version: 20.0 Level: LLT Classification code 10061986 Term: SARS System Organ Class: 100000004862

Interventions

Trade Name: Lopinavir/Ritonavir Product Name: Lopinavir/Ritonavir Pharmaceutical Form: Coated tablet Pharmaceutical form of the placebo: Coated tablet Route of administration of the placebo: Oral use

Eligibility

Sex/Gender

All

Inclusion criteria

Inclusion criteria: - Adult Healthcare workers (HCWs) (physicians, nurses, assistant nurses, dentists, physiotherapists, and midwives) - HCWs 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 - HCWs 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 Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 1200 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range

Exclusion criteria

Exclusion criteria: - HCWs 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 HCV infection treated by direct antiviral drugs or with hypothyroidism that need hormonal substitution, or retinopathy or known to have hypercholesterolemia hypertriglyceridemia - Pregnant HCW - Breastfeeding HCW - HCW taking comedications known to have interactions with LPV/r according to the official characteristics of the product See sessions 4.3 Contraindications and 4.5 Interaction with other medicinal products and other forms of interaction Lopinavir and ritonavir are both inhibitors of the P450 isoform CYP3A in vitro. Co-administration of LPV/r and medicinal products primarily metabolised by CYP3A may result in increased plasma concentrations of the other medicinal product, which could increase or prolong its therapeutic and adverse reactions. LPV/r does not inhibit CYP2D6, CYP2C9, CYP2C19, CYP2E1, CYP2B6 or CYP1A2 at clinically relevant concentrations (see section 4.3). LPV/r has been shown in vivo to induce its own metabolism and to increase the biotransformation of some medicinal products metabolised by cytochrome P450 enzymes (including CYP2C9 and CYP2C19) and by glucuronidation. This may result in lowered plasma concentrations and potential decrease of efficacy of co-administered medicinal products - HCW taking comedications known to have interactions with hydroxychloroquine according to the official characteristics of the product

Design outcomes

Primary

Measure	Time frame
Secondary Objective: 1. To evaluate the occurrence of adverse events in each arm, 2. To evaluate the discontinuation rates of the investigational drug in each arm, 3. To evaluate the adherence of participants to study drug, 4. To evaluate the incidence of symptomatic cases of SARS-CoV-2 infection in each arm, 5. To evaluate the incidence of asymptomatic cases of SARS-CoV-2 infection in each arm, at to 2,5 months after randomization, 6. To evaluate the incidence of severe cases of SARS-CoV-2 infection in each arm. ;Primary end point(s): The primary endpoint is the 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 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.;Timepoint(s) of evaluation of this end point: Day: 7, 14, 21, 28, 35, 42, 49, 57, 71 after the start of the drug;Main Objective: To explore whether a 2-month treatment with either LPV/r or hydroxychloroquine may reduce the incidence of symptomatic or asymptomatic infection by SARS-CoV-2, as compared to their placebo in healthcare workers exposed to SARS-CoV-2.	—

Measure

Time frame

Secondary Objective: 1. To evaluate the occurrence of adverse events in each arm, 2. To evaluate the discontinuation rates of the investigational drug in each arm, 3. To evaluate the adherence of participants to study drug, 4. To evaluate the incidence of symptomatic cases of SARS-CoV-2 infection in each arm, 5. To evaluate the incidence of asymptomatic cases of SARS-CoV-2 infection in each arm, at to 2,5 months after randomization, 6. To evaluate the incidence of severe cases of SARS-CoV-2 infection in each arm. ;Primary end point(s): The primary endpoint is the 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 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.;Timepoint(s) of evaluation of this end point: Day: 7, 14, 21, 28, 35, 42, 49, 57, 71 after the start of the drug;Main Objective: To explore whether a 2-month treatment with either LPV/r or hydroxychloroquine may reduce the incidence of symptomatic or asymptomatic infection by SARS-CoV-2, as compared to their placebo in healthcare workers exposed to SARS-CoV-2.

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Secondary

Measure	Time frame
Secondary end point(s): 1. 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. Number of treatment discontinuations in each arm 3. Treatment adherence rate, which 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. 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. 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 • a 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. 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 50 %.;Timepoint(s) of evaluation of this end point: Day: 7, 14, 21, 28, 35, 42, 49, 57, 71 after the start of	—

Measure

Time frame

Secondary end point(s): 1. 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. Number of treatment discontinuations in each arm 3. Treatment adherence rate, which 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. 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. 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 • a 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. 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 50 %.;Timepoint(s) of evaluation of this end point: Day: 7, 14, 21, 28, 35, 42, 49, 57, 71 after the start of

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Countries

France

Contacts

Public ContactProject manager

CHU Saint Etienne

arnauld.garcin@chu-st-etienne.fr33(0)477120286

Outcome results

None listed

Source: EU CTR (via WHO ICTRP) · Data processed: Feb 4, 2026