Clinical trial NCT04608201: Evaluation of the Efficacy of Nicotine Patches in SARS-CoV2 (COVID-19) Infection in Hospitalized Patients
Official title: Evaluation of the Efficacy of Nicotine Patches in SARS-CoV2 (COVID-19) Infection in Hospitalized Patients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: SARS-COV2
Keywords: SARS-COV2
COVID19
NICOTINE
transdermal patch
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
First posted: 2020-10-29
Enrollment: 32
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. To current knowledge, there is no treatment yet that that can prevent infection from SARS-COV-2 virus, nor the disease progression to a severe form.

Daily active smokers are rare among outpatients or hospitalized COVID-19 patients.

Several arguments suggest that nicotine could be responsible for this protective effect thank to the nicotinic acetylcholine receptor (nAChR).

Based on epidemiological data and experimental data from scientific literature, we hypothesize that nicotine could inhibit the penetration and spread of the virus and improve the management of COVID19 , particularly in hospitalized patients to prevent adverse outcomes (death, transfer to intensive care unit, care limitation, mechanical ventilation an high flow oxygen).


Eligibility criteria: Inclusion Criteria:

* Age ≥ 18 years
* Patients hospitalized for less than 72 hours
* Non-smoking and non-vaping patients (for former smokers or former vapers: abstinent for at least 12 months)
* Documented diagnosis of COVID19
* Lung disease suggestive of COVID-19 on chest scanner or need for oxygen therapy
* Obtaining, informed and signed consent
* Affiliated to a social security scheme or beneficiary of such a scheme (except AME)

Exclusion Criteria:

* WHO 10-point Clinical Progression Scale score \> 5 (patient on non-invasive or mechanical ventilation, patient in need of high-flow oxygen therapy)
* Indication of transfer to intensive care unit (oxygen therapy\> 8 L / min ; out or not carried out due to LATA)
* Current treatment with nicotine replacement therapy, bupropion or varenicline in the last 30 days
* Known addiction problem to alcohol or other substances
* Contraindication for nicotine patches:

  * pregnant or breastfeeding woman
  * lack of effective contraception for women of childbearing age
  * Generalized skin pathologies that may 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 angina
  * Severe cardiac arrhythmia (defined by wearing an automatic implantable defibrillator)
  * Known obliterating peripheral arterial disease
  * Known severe heart failure with an ejection fraction \<30%)
  * Known severe renal (ClCr \<30 ml / min) or hepatic (Child C) impairment
  * Known pheochromocytoma
  * Known uncontrolled hyperthyroidism
  * Esophagitis due to gastroesophageal reflux disease or an active peptic ulcer
* Patient included in another interventional trial evaluating a health product
* Patient under guardianship or curatorship
* Patient deprived of liberty by judicial or administrative decision

Primary outcomes:
measure: The unfavorable outcome on Day 14
timeFrame: Day 14
Secondary outcomes:
measure: Survival rate
timeFrame: Day 14, Day 28
measure: Proportion of transfer to intensive care unit (ICU)
timeFrame: Day 14, Day 28
measure: Proportion of indication of transfer to intensive care unit (carried out or not in case of LATA)
timeFrame: Day 14, Day 28
measure: Number of days living without mechanical ventilation
timeFrame: Day 14, Day 28
measure: Number of days living without non-invasive ventilation and mechanical ventilation
timeFrame: Day 4, Day 14, Day 28
measure: Proportion of patient with a score higher than 6 on the World Health Organization 10-point Clinical Progression Scale
timeFrame: Day 14
measure: Duration of hospitalization
timeFrame: Fom day 1 up to 3 month
measure: Proportion of patient in each category of the World Health Organization 10-point Clinical Progression Scale
timeFrame: Day 7, Day 14 and Day 28
measure: Proportion of patient in each category of the National Early Warning Scale (NEWS) 2
timeFrame: Day 7, Day14 and Day28 (or the day of discharge from hospital)
measure: Proportion of patient with a SARS-CoV-2 viral load detection
timeFrame: Day 7 or the day of discharge from hospital if before day 7
measure: Mean evolution of blood count
timeFrame: At randomization then every 3 days until discharge, or up to 5 weeks
measure: Mean evolution of platelets
timeFrame: At randomization then every 3 days until discharge, or up to 5 weeks
measure: Mean evolution of blood ionogram
timeFrame: At randomization then every 3 days until discharge, or up to 5 weeks
measure: Mean evolution of glycemia
timeFrame: At randomization then every 3 days until discharge, or up to 5 weeks
measure: Mean evolution of serum creatinine
timeFrame: At randomization then every 3 days until discharge, or up to 5 weeks
measure: Mean evolution of C reactive protein
timeFrame: At randomization then every 3 days until discharge, or up to 5 weeks
measure: Mean evolution of Interleukin 6 (IL-6)
timeFrame: At randomization then every 3 days until discharge, or up to 5 weeks
measure: Mean evolution of oxygen requirements (number of liters / min)
timeFrame: At randomization then every 3 days until discharge, or up to 5 weeks
measure: Mean evolution of SaO2
timeFrame: At randomization then every 3 days until discharge, or up to 5 weeks
measure: Proportion of active smoker or active vapers or taking nicotine substitutes documented by examination
timeFrame: Week 2 after treatment decrease, Week 8 after treatment decrease
measure: Proportion of active smoker or active vapers or taking nicotine substitutes documented by urinary cotinine
timeFrame: Week 8 after treatment decrease
measure: Mean score of Desire to smoke defined by French Tobacco Craving questionnaire (FTCQ12 )
timeFrame: Week 2 after treatment decrease, Week 8 after treatment decrease
measure: Mean score of Cigarette Withdrawal Scale (CWS)
timeFrame: Week 2 after treatment decrease, Week 8 after treatment decrease
measure: Mean score of Hospital anxiety and depression scale (HAD)
timeFrame: Week 2 after treatment decrease, Week 8 after treatment decrease
measure: Mean score of Positive and Negative Affect Schedule (PANAS)
timeFrame: Week 2 after treatment decrease, Week 8 after treatment decrease
measure: Mean score of Insomnia severity scale (ISI)
timeFrame: Week 2 after treatment decrease, Week 8 after treatment decrease
measure: weight evolution
timeFrame: Day 1, Week 2 after treatment decrease, Week 8 after treatment decrease
Other outcomes:
Locations:
city: Paris
country: France
facility: Hospital Pitié-Salpêtrière - AP-HP
Study officials:
affiliation: Assistance Publique - Hôpitaux de Paris
name: Valérie POURCHER, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: