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

Assistance Publique - Hôpitaux de Paris32 enrolled

Overview

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).

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Enrollment

Conditions

SARS-COV2

Interventions

Treatment involves escalating doses to the target dose of 14 mg / day 1. / Dose escalation: * Level 1: 3.5 mg/day (1/2 patch) for 2 days (D1 and D2) * Level 2: 7 mg/day (1 patch) for 2 days (D3 and D4) * Level 3: 10.5 mg/day (1.5 patch) for 2 days (D5 and D6) * Level 4: target dose = 14 mg/day (from D7 to discharge from hospital + 1 week or maximum 5 weeks after the start of treatment) 2. / Decrease in dose (1 week after exit from hospital or maximum 5 weeks after the start of treatment): Decrease of 3.5 mg (1/2 patch) per week (over 3 weeks maximum)

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Outcomes

Primary Outcomes

The unfavorable outcome on Day 14

Defined by scores higher than 5 on the World Health Organization 10-point Clinical Progression Scale (WHO-CPS) on day 14

Time frame: Day 14

Secondary Outcomes

Survival rate

Time frame: Day 14, Day 28

Proportion of transfer to intensive care unit (ICU)

Time frame: Day 14, Day 28

Proportion of indication of transfer to intensive care unit (carried out or not in case of LATA)

Time frame: Day 14, Day 28

Number of days living without mechanical ventilation

Time frame: Day 14, Day 28

Number of days living without non-invasive ventilation and mechanical ventilation

Time frame: Day 4, Day 14, Day 28

Proportion of patient with a score higher than 6 on the World Health Organization 10-point Clinical Progression Scale

Time frame: Day 14

Duration of hospitalization

Time frame: Fom day 1 up to 3 month

Proportion of patient in each category of the World Health Organization 10-point Clinical Progression Scale

Time frame: Day 7, Day 14 and Day 28

Proportion of patient in each category of the National Early Warning Scale (NEWS) 2

Time frame: Day 7, Day14 and Day28 (or the day of discharge from hospital)

Proportion of patient with a SARS-CoV-2 viral load detection

Time frame: Day 7 or the day of discharge from hospital if before day 7

Mean evolution of blood count