Clinical trial NCT04583410: Efficacy of Nicotine in Preventing COVID-19 Infection
Official title: Efficacy of Nicotine in Preventing COVID-19 Infection
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Covid19
SARS-Associated Coronavirus as Cause of Disease Classified Elsewhere
Keywords: Covid19
SARS-COV2
Preventing infection
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
First posted: 2020-10-12
Enrollment: 1633
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The coronavirus disease (COVID-19) epidemic represents a major therapeutic challenge. The highly contagious severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) and the long duration of the disease have led to a massive influx of patients admitted in health services and intensive care units.

According to current knowledge, there are no treatments that prevent the spread of the infection, especially in exposed populations, or the disease progression to a severe form.

Daily active smokers are infrequent among outpatients or hospitalized patients with COVID-19. Several arguments suggest that nicotine is responsible for this protective effect via the nicotinic acetylcholine receptor (nAChR).

Nicotine may inhibit the penetration and spread of the virus and have a prophylactic effect in COVID-19 infection.

However, the epidemic is progressing throughout French territory and new variants (in particular the "English B1. 1.7 variant of SARS-COV-2") much more contagious run a risk of accelerating the epidemic in the population. The anti-SARS-COV-2 vaccines recently launched (or being evaluated) represent great hope in this health crisis, but trials were only able to show their effectiveness on symptomatic forms of SARS-COV-2 infection. On the one hand, the vaccination compaign for the entire population requires many months,which leaves many unprotected subjects waiting. In addition, there is currently no evidence of a protective role of vaccines against asymptomatic forms of COVID-19 and therefore on SARS-COV-2 transmission. Finally, the nicotine patches may protect people in hight-risk areas/periods until they are vaccinated (if they accept it and are eligible for it) and in the post-vaccination weeks necessary for the effectiveness of the vaccine,which reinforces the importance of evaluating this alternative prevention strategy, in the context of the arrival of vaccines


Eligibility criteria: Inclusion Criteria:

1. Aged 18 or over
2. May be followed for the duration of the study
3. Obtaining free, informed and signed consent
4. Affiliated to a social security scheme or beneficiary of such a scheme (except AME)
5. Non-smoker and non-vaping (for former smokers or vapers: abstinent for at least 12 months)

Exclusion Criteria:

1. Symptoms suggestive of COVID-19 on the day of inclusion or in the past 14 days
2. Documented history of COVID-19 and / or positive SARS-COV2 serology before the day of inclusion
3. Treatment ongoing with nicotine replacement therapy, varenicline or bupropion within 30 days before inclusion
4. Known addiction problem to alcohol (defined by AUDIT-C \> or = 10) or other substances.
5. Vaccinated against COVID19 infection.
6. Contraindications for nicotine patches:

   * pregnant woman (negative pregnancy test on inclusion) or breastfeeding woman
   * lack of effective contraception for women of childbearing potential
   * Generalized skin conditions that can interfere with the use of a transdermal patch
   * stroke or myocardial infarction or acute coronary syndrome for less than 3 months
   * allergy to nicotine or to one of the excipients of the transdermal patch
   * Uncontrolled high blood pressure
   * Unstable or worsening angor
   * Severe cardiac arrhythmia (defined by wearing an automatic implantable defibrillator)
   * Obliterating peripheral arterial disease
   * Known severe heart failure
   * Known severe renal or hepatic impairment,
   * Pheochromocytoma
   * Uncontrolled hyperthyroidism
   * Esophagitis due to gastroesophageal reflux disease or active peptic ulcer

     7 Already included in an interventional trial evaluating a health product 8 Staff under guardianship or curatorship or deprived of their liberty by a judicial or administrative decision 9 Do not have a smartphone

Primary outcomes:
measure: SARS-COV2 seroconversion between W0 and W19 after randomization
timeFrame: Between week 0 and week 19
Secondary outcomes:
measure: Proportion of documented symptomatic COVID-19 infection
timeFrame: Week 8, Week16
measure: SARS-COV2 seroconversion
timeFrame: Week 16
measure: Asymptomatic COVID-19 infection proportion at week 14
timeFrame: Week 14
measure: Proportion of severe COVID-19 infection
timeFrame: Week 8, Week16
measure: Number of sick leaves for a COVID-19 infection
timeFrame: Week 16
measure: Number of days off during sick leaves for a COVID-19 infection
timeFrame: Week 16
measure: Proportion of AE, SAE
timeFrame: From inclusion and week 25
measure: Intensity and frequency of nausea, dizziness, feeling of empty head, headache, vomiting
timeFrame: Week 25
measure: Proportion of active smoker or active vapers or taking nicotine substitutes documented by examination
timeFrame: Week 25
measure: Proportion of active smoker or active vapers or taking nicotine substitutes documented by urinary cotinine
timeFrame: Week 25
measure: Mean score of Desire to smoke defined by French Tobacco Craving scale
timeFrame: Week 25
measure: Mean score of Withdrawal symptoms scale
timeFrame: Week 25
measure: Dosage of cotinine in the urine
timeFrame: Week 8 and 25
measure: Mean score of Fatigue Numeric rating scale
timeFrame: Week 2, week 8, week 16
measure: Weight
timeFrame: Week 8, week 16, week 25
measure: Mean score of Hospital anxiety and depression scale
timeFrame: Week 2, week 8, week 16
measure: Mean score of Insomnia severity scale
timeFrame: Week 2, week 8, week 16
measure: Positive and negative syndrome scale
timeFrame: Week 2, week 8, week 16
Other outcomes:
Locations:
city: Gonesse
country: France
facility: Centre Hospitalier Gonesse
city: Mulhouse
country: France
facility: Groupe Hospitalier de la Région de Mulhouse Sud Alsace
city: Paris
country: France
facility: Hôpital Pitié Salpêtrière - Service de Médecine Interne
city: Paris
country: France
facility: Hôpital Sainte-Anne
Study officials:
affiliation: Assistance Publique - Hôpitaux de Paris
name: Zahir AMOURA, MD
role: PRINCIPAL_INVESTIGATOR
References: