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

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 Overview

• Status: Completed
• Conditions: SARS-COV2
• Intervention / Treatment: Drug: Nicotine 7 mg/ 24h Transdermal Patch - 24 Hour; Drug: Placebo of NICOTINE Transdermal patch

• Study Type: Interventional
• Enrollment (Actual): 32
• Phase: Phase 3

Contacts and Locations

Study Locations

• France
  • Paris, France, 75013
    • Hospital Pitie-Salpetriere - AP-HP

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: NICOTINE transdermal patch; NICOTINE 7 mg / 24h, transdermal patch	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_COMPARATOR: Placebo of NICOTINE transdermal patch; Placebo of nicotine patch	Drug: Placebo of NICOTINE Transdermal patch; Placebo of nicotine patch administered to the same administration schedule as in the experimental arm

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

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

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris
• Investigators: Principal Investigator: Valérie POURCHER, MD, PhD, Assistance Publique - Hôpitaux de Paris

Study record dates

Study Major Dates

• Study Start (ACTUAL): December 9, 2020
• Primary Completion (ACTUAL): November 5, 2021
• Study Completion (ACTUAL): November 5, 2021

Study Registration Dates

• First Submitted: October 23, 2020
• First Submitted That Met QC Criteria: October 28, 2020
• First Posted (ACTUAL): October 29, 2020

Study Record Updates

• Last Update Posted (ACTUAL): February 11, 2022
• Last Update Submitted That Met QC Criteria: February 10, 2022
• Last Verified: February 1, 2022

More Information

Terms related to this study

• Keywords: COVID19; SARS-COV2; transdermal patch; NICOTINE
• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Cholinergic Agents; Ganglionic Stimulants; Nicotinic Agonists; Cholinergic Agonists; Nicotine
• Other Study ID Numbers: APHP200529; 2020-003743-28 (EUDRACT_NUMBER)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No