COVID-19Phase 3reCoVeryNCT04366739
Repurposing of Chlorpromazine in Covid-19 Treatment
A Phase 3 study testing CHLORPROMAZINE (CPZ) in people with COVID-19, run by Centre Hospitalier St Anne at 1 site in France.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- COVID-19
- What is being tested?
- CHLORPROMAZINE (CPZ)
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 1 siteFrance
- Study dates
- 29 Apr 2020to 30 Sep 2020
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 16Show fewer
- 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 locations and contacts
1 site in 1 country.
About this study
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).
Read the detailed 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.
- Conditions
- COVID-19
- Being tested
- CHLORPROMAZINE (CPZ), Standard of Care (SOC)
- Keywords
- COVID-19, Chlorpromazine
- Medical subject headings
- COVID-19
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
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
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
| Study group | Role | What they receive |
|---|---|---|
| CHLORPROMAZINE (CPZ) | Experimental | Standard of Care (SOC) plus CHLORPROMAZINE (CPZ) Receives: 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 Receives: Combination Product: Standard of Care (SOC) |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 28 days
Secondary outcomes (22)
Objective Response Rate (ORR)
Response rate regarding the World Health Organization Ordinal Scale for Clinical Improvement (WHO-OSCI).
This will be a binary outcome defined by clinical conditions improvement assessment from randomization to 28th Day, by the 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).
Measured: 28 days from randomization
All-cause mortality
All-cause mortality rates at Day 28th after randomization
Measured: 28 days after randomization
Duration in days required for hospital discharge
This will be a continuous outcome defined by the amount of time in days between randomization and the hospital discharge
Measured: 28 days after randomization
Duration in days required for National Early Warning Score ≤ 2 maintained 24 hours
This will be a continuous outcome defined by the amount of time in days between randomization and National Early Warning Score ≤ 2 maintained for almost 24 hours
The National Early Warning Score (NEWS) is a score used in the ICU to evaluate the overall severity of the clinical condition of a patient.
Measured: 28 days after randomization
Number of days without oxygen therapy
This will be a continuous outcome defined by the amount of time in days without oxygen therapy
Measured: 28 days after randomization
Incidence of oxygen use, NIV or high flow oxygen therapy
Number of clinical conditions that need a prescription for Oxygen therapy, NIV or high flow oxygen therapy
Measured: 28 days after randomization
Duration in days of oxygen prescription, NIV or high flow oxygen therapy
This will be a continuous outcome defined by the amount of time in days with oxygen therapy, NIV, or high flow oxygen therapy.
Measured: 28 days after randomization
Biochemical response: rate of patients positive for SARS-CoV-2 PCR on a nasopharyngeal sample
Rate of patients positive for SARS-CoV-2 PCR on a nasopharyngeal sample (biobank sample) (day 7) This will be a binary outcome defined by positive or negative results at SARS-CoV-2 PCR on a nasopharyngeal sample
Measured: day 7 from randomization
Biochemical response: viral load of SARS-CoV-2 on a nasopharyngeal sample
This will be a quantitative variable. Biobank sample at day 7
Measured: day 7 from randomization
Biochemical response: serum viral load of SARS-CoV-2
This will be a quantitative variable. Biobank blood sample at D3, D5, D7 then, if hospitalization continues blood sample at D14, D21, and D28
Measured: day: 3,5,7,14,21,28
Biochemical response: C-reactive protein (CRP)
This will be a quantitative variable. Biobank blood sample at D3, D5, D7 then, if hospitalization continues blood sample at D14, D21, and D28
Measured: day: 3,5,7,14,21,28
Biochemical response: blood test for lymphocytes (lymphopenia)
This will be a quantitative variable. Biobank blood sample at D3, D5, D7 then, if hospitalization continues blood sample at D14, D21, and D28
Measured: day: 3,5,7,14,21,28
Parenchymal involvement (chest CT)
Extension score of parenchymal involvement in thoracic computed tomography (CT) (D7)
Measured: day 7
Define the optimal dose of CPZ and its tolerance: rates of serious adverse events
Rates of serious adverse events
Measured: 28 days
Define the optimal dose of CPZ and its tolerance: rates of non-serious side effects
Rates of non-serious side effects
Measured: 28 days
Define the optimal dose of CPZ and its tolerance: anxiety assessment on Global Anxiety - Visual Analog Scale (GA-VAS)
Global Anxiety - Visual Analog Scale (GA-VAS) is a scale for the assessment of anxiety. The 100 mm GA-VAS varies from minimum (not at all anxious) to maximum (Extremely anxious).
This will be a quantitative variable, the distance from the left edge of the line to the mark placed by the patient is measured to the nearest millimeter and used in analyses as the patient's GA-VAS score.
Measured: 28 days
Define the optimal dose of CPZ and its tolerance: Rates of drug discontinuation
Rates of drug discontinuation in all causes under study
Measured: 28 days
Define the optimal dose of CPZ and its tolerance: biological anomalies
NFS, TP TCA, blood ionogram and hepatic check-up, glycemia. This will be a quantitative variable. Biobank blood sample at D3, D5, D7 then, if hospitalization continues blood sample at D14, D21, and D28
Measured: day: 3,5,7,14,21,28
Define the optimal dose of CPZ and its tolerance: ECG abnormalities
Rate of patients with ECG abnormalities at D3, D5, D7 then, if hospitalization continues blood sample at D14, D21, and D28
Measured: day: 3,5,7,14,21,28
Define the optimal dose of CPZ and its tolerance: plasma CPK assessment
plasma CPK assessment at D3, D5, D7 then, if hospitalization continues blood sample at D14, D21, and D28
Measured: day: 3,5,7,14,21,28
Define the optimal dose of CPZ and its tolerance:plasma CPZ assessment
Plasma CPZ assessment at D3, D5, D7 then, if hospitalization continues blood sample at D14, D21, and D28
Measured: day: 3,5,7,14,21,28
Define the optimal dose of CPZ and its tolerance: CPZ dose administered
CPZ dosages administered
Measured: 28 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Apr 2020
- Study start29 Apr 2020 (estimated)
- Primary completion30 Aug 2020 (estimated)
- Study completion30 Sep 2020 (estimated)
Why it stopped: No favourable opinion obtained from the Ethics Committee
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (16)Papers the sponsor has linked to this study.
- Other trials for COVID-19Studies of the same condition, open and under way.
- More trials run by Centre Hospitalier St AnneThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- 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).
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Centre Hospitalier St Anne
- Sponsor type
- University, hospital or other
- Collaborators
- Hôpital Cochin
- Responsible party
- Sponsor
- Investigators
- Marion Plaze, MD, PHD, Principal investigator, Service Hospitalo-Universitaire - GHU PARIS Psychiatrie & Neurosciences
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04366739
- Sponsor's protocol ID
- D20-P016
- Acronym
- reCoVery
- Status last verified
- Apr 2020
- First submitted
- 24 Apr 2020
- Last updated
- 10 Jul 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Blanchard E, Belouzard S, Goueslain L, Wakita T, Dubuisson J, Wychowski C, Rouille Y. Hepatitis C virus entry depends on clathrin-mediated endocytosis. J Virol. 2006 Jul;80(14):6964-72. doi: 10.1128/JVI.00024-06.
PubMed 16809302Burkard C, Verheije MH, Wicht O, van Kasteren SI, van Kuppeveld FJ, Haagmans BL, Pelkmans L, Rottier PJ, Bosch BJ, de Haan CA. Coronavirus cell entry occurs through the endo-/lysosomal pathway in a proteolysis-dependent manner. PLoS Pathog. 2014 Nov 6;10(11):e1004502. doi: 10.1371/journal.ppat.1004502. eCollection 2014 Nov.
PubMed 25375324Calsina-Berna A, Garcia-Gomez G, Gonzalez-Barboteo J, Porta-Sales J. Treatment of chronic hiccups in cancer patients: a systematic review. J Palliat Med. 2012 Oct;15(10):1142-50. doi: 10.1089/jpm.2012.0087. Epub 2012 Aug 14. No abstract available.
PubMed 22891647Chu VC, McElroy LJ, Bauman BE, Whittaker GR. Fluorescence dequenching assays of coronavirus fusion. Adv Exp Med Biol. 2006;581:241-6. doi: 10.1007/978-0-387-33012-9_40. No abstract available.
PubMed 17037536Cong Y, Hart BJ, Gross R, Zhou H, Frieman M, Bollinger L, Wada J, Hensley LE, Jahrling PB, Dyall J, Holbrook MR. MERS-CoV pathogenesis and antiviral efficacy of licensed drugs in human monocyte-derived antigen-presenting cells. PLoS One. 2018 Mar 22;13(3):e0194868. doi: 10.1371/journal.pone.0194868. eCollection 2018.
PubMed 29566060Daniel JA, Chau N, Abdel-Hamid MK, Hu L, von Kleist L, Whiting A, Krishnan S, Maamary P, Joseph SR, Simpson F, Haucke V, McCluskey A, Robinson PJ. Phenothiazine-derived antipsychotic drugs inhibit dynamin and clathrin-mediated endocytosis. Traffic. 2015 Jun;16(6):635-54. doi: 10.1111/tra.12272. Epub 2015 Apr 9.
PubMed 25693808de Wilde AH, Jochmans D, Posthuma CC, Zevenhoven-Dobbe JC, van Nieuwkoop S, Bestebroer TM, van den Hoogen BG, Neyts J, Snijder EJ. Screening of an FDA-approved compound library identifies four small-molecule inhibitors of Middle East respiratory syndrome coronavirus replication in cell culture. Antimicrob Agents Chemother. 2014 Aug;58(8):4875-84. doi: 10.1128/AAC.03011-14. Epub 2014 May 19.
PubMed 24841269Dyall J, Coleman CM, Hart BJ, Venkataraman T, Holbrook MR, Kindrachuk J, Johnson RF, Olinger GG Jr, Jahrling PB, Laidlaw M, Johansen LM, Lear-Rooney CM, Glass PJ, Hensley LE, Frieman MB. Repurposing of clinically developed drugs for treatment of Middle East respiratory syndrome coronavirus infection. Antimicrob Agents Chemother. 2014 Aug;58(8):4885-93. doi: 10.1128/AAC.03036-14. Epub 2014 May 19.
PubMed 24841273Marmura MJ, Silberstein SD, Schwedt TJ. The acute treatment of migraine in adults: the american headache society evidence assessment of migraine pharmacotherapies. Headache. 2015 Jan;55(1):3-20. doi: 10.1111/head.12499.
PubMed 25600718Pohjala L, Utt A, Varjak M, Lulla A, Merits A, Ahola T, Tammela P. Inhibitors of alphavirus entry and replication identified with a stable Chikungunya replicon cell line and virus-based assays. PLoS One. 2011;6(12):e28923. doi: 10.1371/journal.pone.0028923. Epub 2011 Dec 19.
PubMed 22205980Pu Y, Zhang X. Mouse hepatitis virus type 2 enters cells through a clathrin-mediated endocytic pathway independent of Eps15. J Virol. 2008 Aug;82(16):8112-23. doi: 10.1128/JVI.00837-08. Epub 2008 Jun 11.
PubMed 18550663Verity R, Okell LC, Dorigatti I, Winskill P, Whittaker C, Imai N, Cuomo-Dannenburg G, Thompson H, Walker PGT, Fu H, Dighe A, Griffin JT, Baguelin M, Bhatia S, Boonyasiri A, Cori A, Cucunuba Z, FitzJohn R, Gaythorpe K, Green W, Hamlet A, Hinsley W, Laydon D, Nedjati-Gilani G, Riley S, van Elsland S, Volz E, Wang H, Wang Y, Xi X, Donnelly CA, Ghani AC, Ferguson NM. Estimates of the severity of coronavirus disease 2019: a model-based analysis. Lancet Infect Dis. 2020 Jun;20(6):669-677. doi: 10.1016/S1473-3099(20)30243-7. Epub 2020 Mar 30.
PubMed 32240634Wang D, Hu B, Hu C, Zhu F, Liu X, Zhang J, Wang B, Xiang H, Cheng Z, Xiong Y, Zhao Y, Li Y, Wang X, Peng Z. Clinical Characteristics of 138 Hospitalized Patients With 2019 Novel Coronavirus-Infected Pneumonia in Wuhan, China. JAMA. 2020 Mar 17;323(11):1061-1069. doi: 10.1001/jama.2020.1585.
PubMed 32031570Wang LH, Rothberg KG, Anderson RG. Mis-assembly of clathrin lattices on endosomes reveals a regulatory switch for coated pit formation. J Cell Biol. 1993 Dec;123(5):1107-17. doi: 10.1083/jcb.123.5.1107.
PubMed 8245121Weinman D, Nicastro O, Akala O, Friedman BW. Parenteral treatment of episodic tension-type headache: a systematic review. Headache. 2014 Feb;54(2):260-8. doi: 10.1111/head.12287. Epub 2014 Jan 16.
PubMed 24433525
Study at a glance
From the registry record, last updated by the sponsor on 10 Jul 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Repurposing of Chlorpromazine in Covid-19 Treatment
- ClinicalTrials.gov ID
- NCT04366739
- Acronym / sponsor ID
- reCoVery / D20-P016
- Conditions
- COVID-19
- Keywords
- COVID-19, Chlorpromazine
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: No favourable opinion obtained from the Ethics Committee
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Centre Hospitalier St AnneUniversity, hospital or other
- Collaborators
- Hôpital Cochin
- Study start
- 29 Apr 2020 (estimated)
- Primary completion
- 30 Aug 2020 (estimated)
- Study completion
- 30 Sep 2020 (estimated)
- First posted
- 29 Apr 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Detailed 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
- Model description
- 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).
| Arm | Type | Receives |
|---|---|---|
| CHLORPROMAZINE (CPZ) | Experimental | Drug: CHLORPROMAZINE (CPZ), Combination Product: Standard of Care (SOC)Standard of Care (SOC) plus CHLORPROMAZINE (CPZ) |
| standard of care (SOC) | Active comparator | Combination Product: Standard of Care (SOC)In the absence of a reference treatment in COVID-19, the "standard of care" (SOC) is the comparator arm |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (16 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CHLORPROMAZINE (CPZ)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 | Drug | CHLORPROMAZINE (CPZ) |
| Standard of Care (SOC)In the absence of a reference treatment in COVID-19, the "standard of care" (SOC) is the comparison arm | Combination product | CHLORPROMAZINE (CPZ), standard of care (SOC) |
Primary outcome
Time To Response (TTR)
Time frame: 28 days
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.
22 secondary outcomes
Objective Response Rate (ORR)
Time frame: 28 days from randomization
All-cause mortality
Time frame: 28 days after randomization
Duration in days required for hospital discharge
Time frame: 28 days after randomization
Duration in days required for National Early Warning Score ≤ 2 maintained 24 hours
Time frame: 28 days after randomization
Number of days without oxygen therapy
Time frame: 28 days after randomization
Incidence of oxygen use, NIV or high flow oxygen therapy
Time frame: 28 days after randomization
Duration in days of oxygen prescription, NIV or high flow oxygen therapy
Time frame: 28 days after randomization
Biochemical response: rate of patients positive for SARS-CoV-2 PCR on a nasopharyngeal sample
Time frame: day 7 from randomization
Biochemical response: viral load of SARS-CoV-2 on a nasopharyngeal sample
Time frame: day 7 from randomization
Biochemical response: serum viral load of SARS-CoV-2
Time frame: day: 3,5,7,14,21,28
Biochemical response: C-reactive protein (CRP)
Time frame: day: 3,5,7,14,21,28
Biochemical response: blood test for lymphocytes (lymphopenia)
Time frame: day: 3,5,7,14,21,28
Parenchymal involvement (chest CT)
Time frame: day 7
Define the optimal dose of CPZ and its tolerance: rates of serious adverse events
Time frame: 28 days
Define the optimal dose of CPZ and its tolerance: rates of non-serious side effects
Time frame: 28 days
Define the optimal dose of CPZ and its tolerance: anxiety assessment on Global Anxiety - Visual Analog Scale (GA-VAS)
Time frame: 28 days
Define the optimal dose of CPZ and its tolerance: Rates of drug discontinuation
Time frame: 28 days
Define the optimal dose of CPZ and its tolerance: biological anomalies
Time frame: day: 3,5,7,14,21,28
Define the optimal dose of CPZ and its tolerance: ECG abnormalities
Time frame: day: 3,5,7,14,21,28
Define the optimal dose of CPZ and its tolerance: plasma CPK assessment
Time frame: day: 3,5,7,14,21,28
Define the optimal dose of CPZ and its tolerance:plasma CPZ assessment
Time frame: day: 3,5,7,14,21,28
Define the optimal dose of CPZ and its tolerance: CPZ dose administered
Time frame: 28 days
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Jul 2024.
- Background: PubMed 16809302Blanchard E, Belouzard S, Goueslain L, Wakita T, Dubuisson J, Wychowski C, Rouille Y. Hepatitis C virus entry depends on clathrin-mediated endocytosis. J Virol. 2006 Jul;80(14):6964-72. doi: 10.1128/JVI.00024-06.
- Background: PubMed 25375324Burkard C, Verheije MH, Wicht O, van Kasteren SI, van Kuppeveld FJ, Haagmans BL, Pelkmans L, Rottier PJ, Bosch BJ, de Haan CA. Coronavirus cell entry occurs through the endo-/lysosomal pathway in a proteolysis-dependent manner. PLoS Pathog. 2014 Nov 6;10(11):e1004502. doi: 10.1371/journal.ppat.1004502. eCollection 2014 Nov.
- Background: PubMed 22891647Calsina-Berna A, Garcia-Gomez G, Gonzalez-Barboteo J, Porta-Sales J. Treatment of chronic hiccups in cancer patients: a systematic review. J Palliat Med. 2012 Oct;15(10):1142-50. doi: 10.1089/jpm.2012.0087. Epub 2012 Aug 14. No abstract available.
- Background: PubMed 17037536Chu VC, McElroy LJ, Bauman BE, Whittaker GR. Fluorescence dequenching assays of coronavirus fusion. Adv Exp Med Biol. 2006;581:241-6. doi: 10.1007/978-0-387-33012-9_40. No abstract available.
- Background: PubMed 29566060Cong Y, Hart BJ, Gross R, Zhou H, Frieman M, Bollinger L, Wada J, Hensley LE, Jahrling PB, Dyall J, Holbrook MR. MERS-CoV pathogenesis and antiviral efficacy of licensed drugs in human monocyte-derived antigen-presenting cells. PLoS One. 2018 Mar 22;13(3):e0194868. doi: 10.1371/journal.pone.0194868. eCollection 2018.
- Background: PubMed 25693808Daniel JA, Chau N, Abdel-Hamid MK, Hu L, von Kleist L, Whiting A, Krishnan S, Maamary P, Joseph SR, Simpson F, Haucke V, McCluskey A, Robinson PJ. Phenothiazine-derived antipsychotic drugs inhibit dynamin and clathrin-mediated endocytosis. Traffic. 2015 Jun;16(6):635-54. doi: 10.1111/tra.12272. Epub 2015 Apr 9.
- Background: PubMed 24841269de Wilde AH, Jochmans D, Posthuma CC, Zevenhoven-Dobbe JC, van Nieuwkoop S, Bestebroer TM, van den Hoogen BG, Neyts J, Snijder EJ. Screening of an FDA-approved compound library identifies four small-molecule inhibitors of Middle East respiratory syndrome coronavirus replication in cell culture. Antimicrob Agents Chemother. 2014 Aug;58(8):4875-84. doi: 10.1128/AAC.03011-14. Epub 2014 May 19.
- Background: PubMed 24841273Dyall J, Coleman CM, Hart BJ, Venkataraman T, Holbrook MR, Kindrachuk J, Johnson RF, Olinger GG Jr, Jahrling PB, Laidlaw M, Johansen LM, Lear-Rooney CM, Glass PJ, Hensley LE, Frieman MB. Repurposing of clinically developed drugs for treatment of Middle East respiratory syndrome coronavirus infection. Antimicrob Agents Chemother. 2014 Aug;58(8):4885-93. doi: 10.1128/AAC.03036-14. Epub 2014 May 19.
- Background: PubMed 25600718Marmura MJ, Silberstein SD, Schwedt TJ. The acute treatment of migraine in adults: the american headache society evidence assessment of migraine pharmacotherapies. Headache. 2015 Jan;55(1):3-20. doi: 10.1111/head.12499.
- Background: PubMed 22205980Pohjala L, Utt A, Varjak M, Lulla A, Merits A, Ahola T, Tammela P. Inhibitors of alphavirus entry and replication identified with a stable Chikungunya replicon cell line and virus-based assays. PLoS One. 2011;6(12):e28923. doi: 10.1371/journal.pone.0028923. Epub 2011 Dec 19.
- Background: PubMed 18550663Pu Y, Zhang X. Mouse hepatitis virus type 2 enters cells through a clathrin-mediated endocytic pathway independent of Eps15. J Virol. 2008 Aug;82(16):8112-23. doi: 10.1128/JVI.00837-08. Epub 2008 Jun 11.
- Background: PubMed 32240634Verity R, Okell LC, Dorigatti I, Winskill P, Whittaker C, Imai N, Cuomo-Dannenburg G, Thompson H, Walker PGT, Fu H, Dighe A, Griffin JT, Baguelin M, Bhatia S, Boonyasiri A, Cori A, Cucunuba Z, FitzJohn R, Gaythorpe K, Green W, Hamlet A, Hinsley W, Laydon D, Nedjati-Gilani G, Riley S, van Elsland S, Volz E, Wang H, Wang Y, Xi X, Donnelly CA, Ghani AC, Ferguson NM. Estimates of the severity of coronavirus disease 2019: a model-based analysis. Lancet Infect Dis. 2020 Jun;20(6):669-677. doi: 10.1016/S1473-3099(20)30243-7. Epub 2020 Mar 30.
Related trials for COVID-19
Not yet recruitingPhase 1
Phase I Open-Label Safety Trial of Pembrolizumab for Neurological Post- Acute Sequelae of SARS-CoV-2 (PD1-PASC I)
Post-Acute COVID-19 Syndrome
Active, not recruitingPhase 1
A Safety and Immunogenicity Trial of OCU500, ChAd36 Vector Encoding SARS-CoV-2 Spike Vaccine Via Intranasal and Inhalational Routes in Previously Vaccinated Adults
COVID-19
Active, not recruiting
Intervention to Address Disparate Mental Health Consequences of COVID-19 Pandemic on Latinx and African Newcomers
Mental Health Issue, Mental Health Disorder
Recruiting
Home-Based Exercise Tele-Rehabilitation After COVID-19
Post SARS-CoV2 (COVID-19)
Not yet recruitingPhase 1
A Safety, Reactogenicity and Immunogenicity Trial of RVX-sCPD9 Booster Intranasal COVID-19 Vaccine
COVID -19
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Marion Plaze, MD, PHD principal investigator
Service Hospitalo-Universitaire - GHU PARIS Psychiatrie & Neurosciences
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing CHLORPROMAZINE (CPZ) in people with COVID-19, run by Centre Hospitalier St Anne at 1 site in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 10 Jul 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Time To Response (TTR) (time frame: 28 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04366739, which also lists 16 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Jul 2024.