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.
Drug: Patch, Nicotine
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
Drug: Patch, Placebo
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
Inclusion Criteria:
1. Patient ≥ 18 years
2. Documented diagnosis of COVID 19 (according to the tests referenced on the list
published on the website : https://covid-19.sante.gouv.fr.tests)
3. Hospitalized in intensive care unit, intubated and mechanically ventilated for less
than 48 hours
4. Non-smoker and non-vaping or abstinent patient for at least 12 months
5. Obtain written informed consent from a relative / relative / support person. In the
absence of a close/relative/trusted person, the patient may be included according to
the emergency procedure by the investigating doctor.
6. Affiliated to a social security scheme or beneficiary of such a scheme (AME excluded)
Exclusion Criteria:
1. Chronic respiratory failure defined by PaCO2> 60 mmHg in ambulatory patients
(respiratory parameters at baseline).
2. Mechanical ventilation at home (non-invasive mechanical ventilation or via a
tracheostomy) with the exception of CPAP / BIPAP used only for sleep apnea syndromes
3. Predictable mechanical ventilation duration <48 hours
4. Moribund patient or death expected on the day of randomization, or with a SAPS II
score> 90
5. Cerebral deficiency with dilated areactive pupils or irreversible neurological
pathology.
6. Other concomitant severe pathology with an estimated life expectancy of less than 1
year
7. Treatment with nicotine replacement therapy or varenicline or bupropion ongoing
8. Contraindication for nicotine patches:
- Pregnant or breastfeeding women
- Allergy to nicotine or to one of the excipients of the transdermal patch
- Generalized skin pathologies
- Cerebrovascular accident or acute coronary syndrome for less than 3 months
- Pheochromocytoma
- Unstable or worsening angor
- Severe cardiac arrhythmia (Defined by wearing an automatic implantable
defibrillator)
- Known severe heart failure (Defined, for this study, by systolic LV dysfunction
with an LV ejection fraction (LVEF) of less than 30%)
- Severe renal failure (Defined by KDIGO stage 3)
- Severe hepatic impairment (Defined by a factor V <30%)
- Arteriopathy obliterating of the lower limbs stage III and IV
- Uncontrolled hyperthyroidism
- Gastroduodenal esophagitis or ulcer undergoing treatment or active
9. Patient under guardianship or curatorship
10. Patient deprived of liberty by judicial or administrative decision
11. Patient included in another interventional trial evaluating a health product
Centre Hospitalier Victor Dupouy - Service de Réanimation polyvalente et USC
Argenteuil, France
CHRU de Besançon - Service de Médecine Intensive Réanimation
Besançon, France
Centre Hospitalier Sud Francilien - Service de réanimation
Corbeil-Essonnes, France
CHU Dijon - Hôpital François Miterrand Service de Médecine Intensive Réanimation
Dijon, France
Hôpital Simone VEIL - Service d'Anesthésie-Réanimation
Eaubonne, France
Grand Hôpital de l'Est Francilien - Site Jossigny - Réanimation
Jossigny, France
Hôpital Bicêtre - Service de Médecine Intensive Réanimation
Le Kremlin-Bicêtre, France
Grand Hôpital de l'Est Francilien Site Meaux - Service de Réanimation Médico-Chirurgicale
Meaux, France
Groupement Hospitalier de la Région de Mulhouse Sud Alsace - Hop Emile MULLER
Mulhouse, France
CHU Nice - Hôpital L'Archet 1 - Service de Médecine Intensive Réanimation
Nice, France
CHR Orléans Service de Médecine Intensive Réanimation
Orléans, France
Hôpital Pitié Salpêtrière - ICU
Paris, France
Hôpital Pitié Salpêtrière - Intensive care unit
Paris, France
Institut Mutualiste Montsouris Service de Réanimation Polyvalente
Paris, France
Hôpital Tenon - Service de Médecine Intensive Réanimation
Paris, France
Centre Hospitalier René Dubos - Service de Réanimation Médico-Chirurgicale
Pontoise, France
Hôpital DELAFONTAINE Service de Médecine Intensive Réanimation
Saint-Denis, France
Médipôle Hôpital Privé - MHP Service de Médecine Intensive Réanimation
Villeurbanne, France
Alain COMBES, MD, Principal Investigator
Assistance Publique - Hôpitaux de Paris