Repurposing of Chlorpromazine in Covid-19 Treatment

NCT04366739 | Withdrawn Phase 3 DMC

• 1 other identifier: D20-P016
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

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).

Conditions

COVID-19

Keywords

COVID-19; Chlorpromazine

Outcome Measures

Primary Outcomes (1)

• Time To Response (TTR)

  The primary endpoint is the time to response (TTR) in days, from randomization to 28th day. By response to treatment is meant the reduction of at least one severity level on the World Health Organization Ordinal Scale for Clinical Improvement (WHO-OSCI) The WHO-OSCI is an ordinal scale of 9 severity levels (from 0 to 8) for COVID-19. This scale was established by the WHO, which recommends its use for any therapeutic study on COVID-19. This will be a continuous outcome defined by the amount of time between randomization to the first response. This will be treated as a time-to-event with possible censoring.

  28 days

Secondary Outcomes (22)

• Objective Response Rate (ORR)

  28 days from randomization

• All-cause mortality

  28 days after randomization

• Duration in days required for hospital discharge

  28 days after randomization

• Duration in days required for National Early Warning Score ≤ 2 maintained 24 hours

  28 days after randomization

• Number of days without oxygen therapy

  28 days after randomization

Other Outcomes (1)

• Evaluate the biological parameters to treatment response (biobank constitution for carrying out cytokine assays, lymphocyte profiles in flow cytometry and additional explorations according to the evolution of knowledge on COVID-19)

  day: 1, 3,5,7,14,21,28

Study Arms (2)

CHLORPROMAZINE (CPZ)

EXPERIMENTAL

Standard of Care (SOC) plus CHLORPROMAZINE (CPZ)

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

standard of care (SOC)

ACTIVE COMPARATOR

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

Combination Product: Standard of Care (SOC)

Interventions

CHLORPROMAZINE (CPZ) DRUG

Drug List 1, AMM obtained in 1952, AMM 3400930571187 1952/90, RCP revised 22/08/2019 Administration: oral route, if the clinical condition requires it, intravenous administration. Initial dosage: 75 mg per day orally (or 37.5 mg per day orally in subjects 75 years of age or older). Then: titration up to the maximum tolerated dose, with a minimum of 12.5 mg and a maximum of 300 mg per day by the oral administration (or 600 mg per day by the oral in certain exceptional cases which also correspond to the CPM CPM marketing authorization indications); or from 6.25 to 150 mg per day intravenously. Duration of treatment: until healing criteria are obtained (≥ 8 days from the onset of COVID-19 symptoms AND ≥ 48 hours of apyrexia and absence of dyspnea) or 21 days maximum

CHLORPROMAZINE (CPZ)

Standard of Care (SOC) COMBINATION_PRODUCT

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

CHLORPROMAZINE (CPZ); standard of care (SOC)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Biological and/or radiological diagnosis of COVID-19 infection
• 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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• Centre Hospitalier St Anne: lead
• Hôpital Cochin: collaborator

Study Sites (1)

Centre Hospitalier Sainte-Anne

Paris, 75014, France

Location

Related Publications (16)

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MeSH Terms

Conditions

COVID-19

Interventions

Chlorpromazine; Standard of Care

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Phenothiazines; Sulfur Compounds; Organic Chemicals; Heterocyclic Compounds, 3-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Quality Indicators, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation

Study Officials

• Marion Plaze, MD, PHD

  Service Hospitalo-Universitaire - GHU PARIS Psychiatrie & Neurosciences

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: The evaluator of the primary endpoint and secondary endpoints relating to the clinical efficacy of CPZ and the evaluator of the biological and radiological effects of the CPZ will be maintained blindly throughout their duration of inclusion. This evaluator will collect clinical data, biological data, and imaging data without knowing the drug treatments delivered to patients. The radiologists responsible for calculating the parenchymal damage score on the thoracic CT scan will be blind to the patient delivered drugs. The biologists responsible for carrying out the analyzes on the biobank will be blind to the patient delivered drugs. The biostatistician responsible for statistical study analysis will be kept blind to the drugs delivered to the subjects.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Allocation: Randomized Intervention Model: Parallel Assignment Intervention Model Description: reCoVery is a multi-center, randomized, single-blind, standard care-controlled (1:1) pilot clinical study to explore the efficacy and safety of chlorpromazine (CPZ) in the treatment of adult subjects with COVID-19-moderate type (WHO-OSCI 3-5).

Study Record Dates

• First Submitted: April 24, 2020
• First Posted: April 29, 2020
• Study Start: April 29, 2020
• Primary Completion: August 30, 2020
• Study Completion: September 30, 2020
• Last Updated: July 10, 2024

Record last verified: 2020-04

Locations

FR (1)