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

NCT04598594 | Completed Phase 3 DMC

• 2 other identifiers: APHP2005372020-003723-42
• Study Type: interventional
• Target: 220
• Locations: 1 country
• Sites: 18

Brief Summary

There is currently no known treatment for COVID19. Active smokers are infrequent among patients with COVID-19 which has led our team to hypothesize that nicotine is responsible for this protective effect via the nicotinic acetylcholine receptor (nAChR). In fact, nAChR possess the ability to modulate ACE2 expression, the cellular doorway for SARS-CoV2. nAChR modulation by the virus would be responsible for the numerous clinical signs observed in COVID-19, including the cytokine storm manifested in intensive care hyperinflammatory patients. Based on epidemiological data and experimental data from scientific literature, our team hypothesize that nicotine could inhibit the penetration and propagation of SARS-CoV2. Our team also claim that nicotine could attenuate the hyperinflammatory response and cytokine storm leading to acute respiratory failure and a probable multi-organ failure associated with COVID19.

Conditions

Covid19; SARS-Associated Coronavirus as Cause of Disease Classified Elsewhere

Keywords

Covid19; SARS-CoV2; Mechanical ventilation; ICU; Nicotine

Outcome Measures

Primary Outcomes (1)

• Mortality

  Day 28

Secondary Outcomes (24)

• Mortality

  Day 60

• Time before successful extubation

  Day 60

• Number of days living without invasive mechanical ventilation

  Day 28

• Composite score incorporating death and the number of days living without mechanical ventilation

  Day 60

• Mean evolution of blood gases

  Day 1 to Day 14

Study Arms (2)

Nicotine patch

EXPERIMENTAL

Drug: Patch, Nicotine

Placebo patch

PLACEBO COMPARATOR

Drug: Patch, Placebo

Interventions

Patch, Nicotine DRUG

Two patches of 7 mg/day Treatment at 14 mg/day during mechanical ventilation since after first successful extubation then, dose decreasing: Week 1: 10,5 mg/day Week 2 : 7 mg/day Week 3 : 3,5 mg/day

Nicotine patch

Patch, Placebo DRUG

Two patches of 7 mg/day Treatment at 14 mg/day during mechanical ventilation since after first successful extubation then, dose decreasing: Week 1: 10,5 mg/day Week 2 : 7 mg/day Week 3 : 3,5 mg/day

Placebo patch

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patient ≥ 18 years
• Documented diagnosis of COVID 19 (according to the tests referenced on the list published on the website : https://covid-19.sante.gouv.fr.tests)
• Hospitalized in intensive care unit, intubated and mechanically ventilated for less than 48 hours
• Non-smoker and non-vaping or abstinent patient for at least 12 months
• Obtain written informed consent from a relative / relative / support person. In the absence of a close/relative/trusted person, the patient may be included according to the emergency procedure by the investigating doctor.
• Affiliated to a social security scheme or beneficiary of such a scheme (AME excluded)

You may not qualify if:

• Chronic respiratory failure defined by PaCO2\> 60 mmHg in ambulatory patients (respiratory parameters at baseline).
• Mechanical ventilation at home (non-invasive mechanical ventilation or via a tracheostomy) with the exception of CPAP / BIPAP used only for sleep apnea syndromes
• Predictable mechanical ventilation duration \<48 hours
• Moribund patient or death expected on the day of randomization, or with a SAPS II score\> 90
• Cerebral deficiency with dilated areactive pupils or irreversible neurological pathology.
• Other concomitant severe pathology with an estimated life expectancy of less than 1 year
• Treatment with nicotine replacement therapy or varenicline or bupropion ongoing
• Contraindication for nicotine patches:
• Pregnant or breastfeeding women
• Allergy to nicotine or to one of the excipients of the transdermal patch
• Generalized skin pathologies
• Cerebrovascular accident or acute coronary syndrome for less than 3 months
• Pheochromocytoma
• Unstable or worsening angor
• Severe cardiac arrhythmia (Defined by wearing an automatic implantable defibrillator)

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead

Study Sites (18)

Centre Hospitalier Victor Dupouy - Service de Réanimation polyvalente et USC

Argenteuil, 95100, France

Location

CHRU de Besançon - Service de Médecine Intensive Réanimation

Besançon, 25030, France

Location

Centre Hospitalier Sud Francilien - Service de réanimation

Corbeil-Essonnes, 91100, France

Location

CHU Dijon - Hôpital François Miterrand Service de Médecine Intensive Réanimation

Dijon, 22033, France

Location

Hôpital Simone VEIL - Service d'Anesthésie-Réanimation

Eaubonne, 95000, France

Location

Grand Hôpital de l'Est Francilien - Site Jossigny - Réanimation

Jossigny, 77600, France

Location

Hôpital Bicêtre - Service de Médecine Intensive Réanimation

Le Kremlin-Bicêtre, 94270, France

Location

Grand Hôpital de l'Est Francilien Site Meaux - Service de Réanimation Médico-Chirurgicale

Meaux, 77104, France

Location

Groupement Hospitalier de la Région de Mulhouse Sud Alsace - Hop Emile MULLER

Mulhouse, 68100, France

Location

CHU Nice - Hôpital L'Archet 1 - Service de Médecine Intensive Réanimation

Nice, 06000, France

Location

CHR Orléans Service de Médecine Intensive Réanimation

Orléans, 45067, France

Location

Hôpital Pitié Salpêtrière - ICU

Paris, 75013, France

Location

Hôpital Pitié Salpêtrière - Intensive care unit

Paris, 75013, France

Location

Institut Mutualiste Montsouris Service de Réanimation Polyvalente

Paris, 75014, France

Location

Hôpital Tenon - Service de Médecine Intensive Réanimation

Paris, 75020, France

Location

Centre Hospitalier René Dubos - Service de Réanimation Médico-Chirurgicale

Pontoise, 95303, France

Location

Hôpital DELAFONTAINE Service de Médecine Intensive Réanimation

Saint-Denis, 93200, France

Location

Médipôle Hôpital Privé - MHP Service de Médecine Intensive Réanimation

Villeurbanne, 69100, France

Location

Related Publications (1)

• Labro G, Tubach F, Belin L, Dubost JL, Osman D, Muller G, Quenot JP, Da Silva D, Zarka J, Turpin M, Mayaux J, Lamer C, Doyen D, Chevrel G, Plantefeve G, Demeret S, Piton G, Manzon C, Ochin E, Gaillard R, Dautzenberg B, Baldacini M, Lebbah S, Miyara M, Pineton de Chambrun M, Amoura Z, Combes A; NICOVID-REA Trial Group. Nicotine patches in patients on mechanical ventilation for severe COVID-19: a randomized, double-blind, placebo-controlled, multicentre trial. Intensive Care Med. 2022 Jul;48(7):876-887. doi: 10.1007/s00134-022-06721-1. Epub 2022 Jun 9.

  PMID: 35676335 DERIVED

MeSH Terms

Conditions

COVID-19

Interventions

Tobacco Use Cessation Devices; Transdermal Patch

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Therapeutics; Equipment and Supplies

Study Officials

• Alain COMBES, MD

  Assistance Publique - Hôpitaux de Paris

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 15, 2020
• First Posted: October 22, 2020
• Study Start: November 6, 2020
• Primary Completion: April 29, 2021
• Study Completion: June 20, 2021
• Last Updated: June 22, 2021

Record last verified: 2021-06

Locations

FR (18)