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| ID | Type | Description | Link |
|---|---|---|---|
| 2020-003723-42 | EudraCT Number |
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There is currently no known treatment for COVID19. Active smokers are infrequent among patients with COVID-19 which has led our team to hypothesize that nicotine is responsible for this protective effect via the nicotinic acetylcholine receptor (nAChR). In fact, nAChR possess the ability to modulate ACE2 expression, the cellular doorway for SARS-CoV2. nAChR modulation by the virus would be responsible for the numerous clinical signs observed in COVID-19, including the cytokine storm manifested in intensive care hyperinflammatory patients.
Based on epidemiological data and experimental data from scientific literature, our team hypothesize that nicotine could inhibit the penetration and propagation of SARS-CoV2. Our team also claim that nicotine could attenuate the hyperinflammatory response and cytokine storm leading to acute respiratory failure and a probable multi-organ failure associated with COVID19.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Nicotine patch | Experimental |
| |
| Placebo patch | Placebo Comparator |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Patch, Nicotine | Drug | Two patches of 7 mg/day Treatment at 14 mg/day during mechanical ventilation since after first successful extubation then, dose decreasing: Week 1: 10,5 mg/day Week 2 : 7 mg/day Week 3 : 3,5 mg/day |
| Measure | Description | Time Frame |
|---|---|---|
| Mortality | Day 28 |
| Measure | Description | Time Frame |
|---|---|---|
| Mortality | Day 60 | |
| Time before successful extubation | Without reintubation or death in the following 48 hours for tracheotomized patients: alive and not ventilated for 48 hours (with death and LATA in competitive risks). |
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Inclusion Criteria:
Exclusion Criteria:
Chronic respiratory failure defined by PaCO2> 60 mmHg in ambulatory patients (respiratory parameters at baseline).
Mechanical ventilation at home (non-invasive mechanical ventilation or via a tracheostomy) with the exception of CPAP / BIPAP used only for sleep apnea syndromes
Predictable mechanical ventilation duration <48 hours
Moribund patient or death expected on the day of randomization, or with a SAPS II score> 90
Cerebral deficiency with dilated areactive pupils or irreversible neurological pathology.
Other concomitant severe pathology with an estimated life expectancy of less than 1 year
Treatment with nicotine replacement therapy or varenicline or bupropion ongoing
Contraindication for nicotine patches:
Patient under guardianship or curatorship
Patient deprived of liberty by judicial or administrative decision
Patient included in another interventional trial evaluating a health product
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| Name | Affiliation | Role |
|---|---|---|
| Alain COMBES, MD | Assistance Publique - Hôpitaux de Paris | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Centre Hospitalier Victor Dupouy - Service de Réanimation polyvalente et USC | Argenteuil | 95100 | France | |||
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 35676335 | Derived | Labro G, Tubach F, Belin L, Dubost JL, Osman D, Muller G, Quenot JP, Da Silva D, Zarka J, Turpin M, Mayaux J, Lamer C, Doyen D, Chevrel G, Plantefeve G, Demeret S, Piton G, Manzon C, Ochin E, Gaillard R, Dautzenberg B, Baldacini M, Lebbah S, Miyara M, Pineton de Chambrun M, Amoura Z, Combes A; NICOVID-REA Trial Group. Nicotine patches in patients on mechanical ventilation for severe COVID-19: a randomized, double-blind, placebo-controlled, multicentre trial. Intensive Care Med. 2022 Jul;48(7):876-887. doi: 10.1007/s00134-022-06721-1. Epub 2022 Jun 9. |
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| Patch, Placebo | Drug | Two patches of 7 mg/day Treatment at 14 mg/day during mechanical ventilation since after first successful extubation then, dose decreasing: Week 1: 10,5 mg/day Week 2 : 7 mg/day Week 3 : 3,5 mg/day |
|
| Day 60 |
| Number of days living without invasive mechanical ventilation | Day 28 |
| Composite score incorporating death and the number of days living without mechanical ventilation | This is a ranked composite score that incorporates death and days free from mechanical ventilation through day 28, calculated in such a manner that death constitutes a worse outcome than fewer days off the ventilator.16 Time free from mechanical ventilation was calculated as the number of days between successful liberation from the ventilator and study day 60. Each patient was compared with every other patient in the study and assigned a score (tie: 0, win: +1, loss: -1) for each pairwise comparison based on whom fared better | Day 60 |
| Mean evolution of blood gases | measured each day from day 1 to day 14 | Day 1 to Day 14 |
| Mean evolution of Tidal Volume (ventilator parameters) | measured each day from day 1 to day 14 | Day 1 to Day 14 |
| Mean evolution of respiratory rate (ventilator parameters) | measured each day from day 1 to day 14 | Day 1 to Day 14 |
| Mean evolution of Positive Expiratory Pressure (ventilator parameters) | measured each day from day 1 to day 14 | Day 1 to Day 14 |
| Mean evolution of plateau pressure (ventilator parameters) | measured each day from day 1 to day 14 | Day 1 to Day 14 |
| Mean evolution of fraction of inspired oxygen (ventilator parameters) | measured each day from day 1 to day 14 | Day 1 to Day 14 |
| Evolution of the Sequential Organ Failure Assessment (SOFA) score and its components by organ | A higher score indicate a worse outcome | Day 1 to Day 28 |
| Number of days alive without organ failure | Day 28, day 60 |
| Duration of hospitalization in intensive care unit | From day 1 up to 3 months |
| Duration of hospitalization in hospital | From day 1 up to 3 months |
| Number of days alive and out of the ICU and hospital | Day 28, day 60 |
| Evolution of viral load | samples taken on D7 and D14 or the day of discharge from intensive care unit if before D14 | Day 7, Day 14 or day of ICU discharge if before day 14 |
| Proportion of active smoker or active vapers or taking nicotine substitutes documented by examination | 2 weeks after treatment decrease, 8 weeks after treatment decrease |
| Proportion of active smoker or active vapers or taking nicotine substitutes documented by urinary cotinine | 2 weeks after treatment decrease, 8 weeks after treatment decrease |
| Mean score of Desire to smoke defined by French Tobacco Craving scale | 2 weeks after treatment decrease, 8 weeks after treatment decrease |
| Mean score of Withdrawal symptoms scale | 2 weeks after treatment decrease, 8 weeks after treatment decrease |
| Mean score of Hospital anxiety and depression scale | 2 weeks after treatment decrease, 8 weeks after treatment decrease |
| Post traumatic stress disorder scale | 2 weeks after treatment decrease, 8 weeks after treatment decrease |
| Mean score of Insomnia severity scale | 2 weeks after treatment decrease |
| Cotinin rate in blood | 8 weeks after treatment decrease |
| CHRU de Besançon - Service de Médecine Intensive Réanimation |
| Besançon |
| 25030 |
| France |
| Centre Hospitalier Sud Francilien - Service de réanimation | Corbeil-Essonnes | 91100 | France |
| CHU Dijon - Hôpital François Miterrand Service de Médecine Intensive Réanimation | Dijon | 22033 | France |
| Hôpital Simone VEIL - Service d'Anesthésie-Réanimation | Eaubonne | 95000 | France |
| Grand Hôpital de l'Est Francilien - Site Jossigny - Réanimation | Jossigny | 77600 | France |
| Hôpital Bicêtre - Service de Médecine Intensive Réanimation | Le Kremlin-Bicêtre | 94270 | France |
| Grand Hôpital de l'Est Francilien Site Meaux - Service de Réanimation Médico-Chirurgicale | Meaux | 77104 | France |
| Groupement Hospitalier de la Région de Mulhouse Sud Alsace - Hop Emile MULLER | Mulhouse | 68100 | France |
| CHU Nice - Hôpital L'Archet 1 - Service de Médecine Intensive Réanimation | Nice | 06000 | France |
| CHR Orléans Service de Médecine Intensive Réanimation | Orléans | 45067 | France |
| Hôpital Pitié Salpêtrière - ICU | Paris | 75013 | France |
| Hôpital Pitié Salpêtrière - Intensive care unit | Paris | 75013 | France |
| Institut Mutualiste Montsouris Service de Réanimation Polyvalente | Paris | 75014 | France |
| Hôpital Tenon - Service de Médecine Intensive Réanimation | Paris | 75020 | France |
| Centre Hospitalier René Dubos - Service de Réanimation Médico-Chirurgicale | Pontoise | 95303 | France |
| Hôpital DELAFONTAINE Service de Médecine Intensive Réanimation | Saint-Denis | 93200 | France |
| Médipôle Hôpital Privé - MHP Service de Médecine Intensive Réanimation | Villeurbanne | 69100 | France |
| ID | Term |
|---|---|
| D000086382 | COVID-19 |
| ID | Term |
|---|---|
| D011024 | Pneumonia, Viral |
| D011014 | Pneumonia |
| D012141 | Respiratory Tract Infections |
| D007239 | Infections |
| D014777 | Virus Diseases |
| D018352 | Coronavirus Infections |
| D003333 | Coronaviridae Infections |
| D030341 | Nidovirales Infections |
| D012327 | RNA Virus Infections |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
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| ID | Term |
|---|---|
| D061485 | Tobacco Use Cessation Devices |
| D057968 | Transdermal Patch |
| ID | Term |
|---|---|
| D013812 | Therapeutics |
| D004864 | Equipment and Supplies |
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