Repurposing of Chlorpromazine in Covid-19 Treatment (reCoVery)

Centre Hospitalier St Anne

Status and phase: Withdrawn; Phase 3

Conditions: COVID-19

Treatments: Drug: CHLORPROMAZINE (CPZ); Combination Product: Standard of Care (SOC)

Study type: Interventional

Funder types: Other

Identifiers

NCT04366739

D20-P016

Details and patient eligibility

About

This study evaluates the effects of the addition of chlorpromazine to the standard therapeutic protocol in COVID-19 patients hospitalized for respiratory symptom management (score 3-5 WHO Ordinal Scale for Clinical Improvement).

Full description

This study evaluates the effects of the addition of chlorpromazine to the standard therapeutic protocol in COVID 19 patients hospitalized for respiratory symptom management (score 3-5 WHO Ordinal Scale for Clinical Improvement).

The investigators have observed in GHU-Paris psychiatry Hospital units (140 beds), significantly lower prevalence of symptomatic and severe forms of COVID-19 in patients (3%) than in the health workers operating in the same facilities (19% of nurses and 18% of physicians). COVID-psychiatry units report similar feedback in France, Spain, and Italy. One hypothesis could be that psychotropic drugs have a protective action on COVID-19 and protect patients from symptomatic and virulent forms of COVID-19.

This hypothesis is consistent with research studies that have shown that several psychotropic drugs inhibit in vitro viral replication of the coronaviruses MERS-CoV and SARS-CoV-1. The SARS-CoV-2 has many characteristics in common with the coronavirus family and has phylogenetic similarities to the SARS-CoV-1 engaged in the 2002-2003 outbreak. It is, therefore, possible that one or more psychotropic drugs having demonstrated efficacy against MERS-CoV and SARS-CoV-1 also have anti-SARS-CoV-2 antiviral activity.

The current global epidemic of COVID-19, with a high number of deaths in many countries, makes it urgent to search drugs potentially useful to reduce the severity and lethality of the infection. Drug repositioning represents a possible alternative to the news medicines discovery. This strategy makes it possible to eliminate many stages of development; it makes it possible to deploy a therapy whose side effects are known and which physicians already well know how to handle.

To confirm the hypothesis of the antiviral action of chlorpromazine on SARS-CoV-2, a preclinical in vitro experiment began in April 2020 at the level III high-security biological laboratory at the Pasteur Institute (in collaboration with the GHU PARIS Psychiatry & Neurosciences). The first results are encouraging and show a marked antiviral effect of chlorpromazine on SARS-CoV-2. Technical replicas are underway to validate these preliminary results.

By integrating all these evidence, the investigators hypothesize that chlorpromazine could decrease the unfavorable evolution of COVID-19 infection when administered at the onset of respiratory signs.

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Biological and/or radiological diagnosis of COVID-19 infection
• WHO-OSCI at 3, 4 or 5 at the time of inclusion
• Benefiting from a social security scheme
• Voluntarily participating in the clinical study; fully understanding and being fully informed of the study and having signed the Informed Consent Form (ICF); willingness and capability to complete all the study procedures

Exclusion criteria

• Treatment with chlorpromazine (CPZ) the month preceding the inclusion visit
• Contraindication to the CPZ:
• Hypersensitivity to the active substance or any of the excipients
• Risk of glaucoma by closing the angle.
• Risk of urinary retention linked to urethroprostatic disorders.
• History of agranulocytosis
• Association with dopaminergic outside Parkinson's (cabergoline, quinagolide), citalopram, escitalopram, domperidone, hydroxyzine, and piperaquine
• Wheat allergy
• Risk of QT prolongation and occurrence of severe ventricular rhythm disorders: the existence of bradycardia, hypokalaemia, long congenital or acquired QT
• History of ischemic stroke
• Treatment with chloroquine or hydroxychloroquine during the inclusion visit or the previous month
• Need for mechanical ventilation linked to COVID-19, during the inclusion visit or the last month
• In the opinion of the clinical team, imminent progression to death within the next 24 hours regardless of treatment
• Psychiatric care under duress
• Protected adults, persons under the protection of justice
• Pregnant or lactating woman

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

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0 participants in 2 patient groups

CHLORPROMAZINE (CPZ)

Experimental group

Description:

Standard of Care (SOC) plus CHLORPROMAZINE (CPZ)

Treatment:

Combination Product: Standard of Care (SOC)

Drug: CHLORPROMAZINE (CPZ)

standard of care (SOC)

Active Comparator group

Description:

In the absence of a reference treatment in COVID-19, the "standard of care" (SOC) is the comparator arm

Treatment:

Combination Product: Standard of Care (SOC)