Evaluation of the Efficacy of Nicotine Patches in SARS-CoV2 (COVID-19) Infection in Intensive Care Unit Patients

Assistance Publique - Hôpitaux de Paris220 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Enrollment

220

Conditions

Covid19 SARS-Associated Coronavirus as Cause of Disease Classified Elsewhere

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Locations (18)

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

...and 8 more locations

Outcomes

Primary Outcomes

Mortality

Time frame: Day 28

Secondary Outcomes

Mortality

Time frame: 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).

Time frame: Day 60

Number of days living without invasive mechanical ventilation

Time frame: 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

Time frame: Day 60

Mean evolution of blood gases