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

SARS-COV2 Clinical Trial

— NICOVID  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04608201
• Other study ID #: APHP200529
• Secondary ID: 2020-003743-28
• Status: Completed
• Phase: Phase 3
• Start date: December 9, 2020
• Est. completion date: November 5, 2021

Study information

• Verified date: February 2022
• Source: Assistance Publique - Hôpitaux de Paris
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 32
• Est. completion date: November 5, 2021
• Est. primary completion date: November 5, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• COVID-19
• SARS-COV2

Intervention

Drug:
• Nicotine 7 mg/ 24h Transdermal Patch - 24 Hour
Treatment involves escalating doses to the target dose of 14 mg / day / 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) / 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)
• Placebo of NICOTINE Transdermal patch
Placebo of nicotine patch administered to the same administration schedule as in the experimental arm

Locations

Country	Name	City	State
France	Hospital Pitié-Salpêtrière - AP-HP	Paris

Sponsors (1)

Lead Sponsor	Collaborator
Assistance Publique - Hôpitaux de Paris

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Day 14
Secondary	Survival rate		Day 14, Day 28
Secondary	Proportion of transfer to intensive care unit (ICU)		Day 14, Day 28
Secondary	Proportion of indication of transfer to intensive care unit (carried out or not in case of LATA)		Day 14, Day 28
Secondary	Number of days living without mechanical ventilation		Day 14, Day 28
Secondary	Number of days living without non-invasive ventilation and mechanical ventilation		Day 4, Day 14, Day 28
Secondary	Proportion of patient with a score higher than 6 on the World Health Organization 10-point Clinical Progression Scale		Day 14
Secondary	Duration of hospitalization		Fom day 1 up to 3 month
Secondary	Proportion of patient in each category of the World Health Organization 10-point Clinical Progression Scale		Day 7, Day 14 and Day 28
Secondary	Proportion of patient in each category of the National Early Warning Scale (NEWS) 2		Day 7, Day14 and Day28 (or the day of discharge from hospital)
Secondary	Proportion of patient with a SARS-CoV-2 viral load detection		Day 7 or the day of discharge from hospital if before day 7
Secondary	Mean evolution of blood count		At randomization then every 3 days until discharge, or up to 5 weeks
Secondary	Mean evolution of platelets		At randomization then every 3 days until discharge, or up to 5 weeks
Secondary	Mean evolution of blood ionogram		At randomization then every 3 days until discharge, or up to 5 weeks
Secondary	Mean evolution of glycemia		At randomization then every 3 days until discharge, or up to 5 weeks
Secondary	Mean evolution of serum creatinine		At randomization then every 3 days until discharge, or up to 5 weeks
Secondary	Mean evolution of C reactive protein		At randomization then every 3 days until discharge, or up to 5 weeks
Secondary	Mean evolution of Interleukin 6 (IL-6)		At randomization then every 3 days until discharge, or up to 5 weeks
Secondary	Mean evolution of oxygen requirements (number of liters / min)		At randomization then every 3 days until discharge, or up to 5 weeks
Secondary	Mean evolution of SaO2		At randomization then every 3 days until discharge, or up to 5 weeks
Secondary	Proportion of active smoker or active vapers or taking nicotine substitutes documented by examination		Week 2 after treatment decrease, Week 8 after treatment decrease
Secondary	Proportion of active smoker or active vapers or taking nicotine substitutes documented by urinary cotinine		Week 8 after treatment decrease
Secondary	Mean score of Desire to smoke defined by French Tobacco Craving questionnaire (FTCQ12 )		Week 2 after treatment decrease, Week 8 after treatment decrease
Secondary	Mean score of Cigarette Withdrawal Scale (CWS)		Week 2 after treatment decrease, Week 8 after treatment decrease
Secondary	Mean score of Hospital anxiety and depression scale (HAD)		Week 2 after treatment decrease, Week 8 after treatment decrease
Secondary	Mean score of Positive and Negative Affect Schedule (PANAS)		Week 2 after treatment decrease, Week 8 after treatment decrease
Secondary	Mean score of Insomnia severity scale (ISI)		Week 2 after treatment decrease, Week 8 after treatment decrease
Secondary	weight evolution		Day 1, Week 2 after treatment decrease, Week 8 after treatment decrease