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

Sponsor
Assistance Publique - Hôpitaux de Paris (Other)
Overall Status
Completed
CT.gov ID
NCT04598594
Collaborator
(none)
220
18
2
7.4
12.2
1.6

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
  • Drug: Patch, Nicotine
  • Drug: Patch, Placebo
Phase 3

Study Design

Study Type:
Interventional
Actual Enrollment :
220 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Double (Participant, Investigator)
Primary Purpose:
Treatment
Official Title:
Evaluation of the Efficacy of Nicotine Patches in SARS-CoV2 (COVID-19) Infection in Intensive Care Unit Patients
Actual Study Start Date :
Nov 6, 2020
Actual Primary Completion Date :
Apr 29, 2021
Actual Study Completion Date :
Jun 20, 2021

Arms and Interventions

Arm Intervention/Treatment
Experimental: Nicotine patch

Drug: Patch, Nicotine
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 Comparator: Placebo patch

Drug: Patch, Placebo
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

Outcome Measures

Primary Outcome Measures

  1. Mortality [Day 28]

Secondary Outcome Measures

  1. Mortality [Day 60]

  2. Time before successful extubation [Day 60]

    Without reintubation or death in the following 48 hours for tracheotomized patients: alive and not ventilated for 48 hours (with death and LATA in competitive risks).

  3. Number of days living without invasive mechanical ventilation [Day 28]

  4. Composite score incorporating death and the number of days living without mechanical ventilation [Day 60]

    This is a ranked composite score that incorporates death and days free from mechanical ventilation through day 28, calculated in such a manner that death constitutes a worse outcome than fewer days off the ventilator.16 Time free from mechanical ventilation was calculated as the number of days between successful liberation from the ventilator and study day 60. Each patient was compared with every other patient in the study and assigned a score (tie: 0, win: +1, loss: -1) for each pairwise comparison based on whom fared better

  5. Mean evolution of blood gases [Day 1 to Day 14]

    measured each day from day 1 to day 14

  6. Mean evolution of Tidal Volume (ventilator parameters) [Day 1 to Day 14]

    measured each day from day 1 to day 14

  7. Mean evolution of respiratory rate (ventilator parameters) [Day 1 to Day 14]

    measured each day from day 1 to day 14

  8. Mean evolution of Positive Expiratory Pressure (ventilator parameters) [Day 1 to Day 14]

    measured each day from day 1 to day 14

  9. Mean evolution of plateau pressure (ventilator parameters) [Day 1 to Day 14]

    measured each day from day 1 to day 14

  10. Mean evolution of fraction of inspired oxygen (ventilator parameters) [Day 1 to Day 14]

    measured each day from day 1 to day 14

  11. Evolution of the Sequential Organ Failure Assessment (SOFA) score and its components by organ [Day 1 to Day 28]

    A higher score indicate a worse outcome

  12. Number of days alive without organ failure [Day 28, day 60]

  13. Duration of hospitalization in intensive care unit [From day 1 up to 3 months]

  14. Duration of hospitalization in hospital [From day 1 up to 3 months]

  15. Number of days alive and out of the ICU and hospital [Day 28, day 60]

  16. Evolution of viral load [Day 7, Day 14 or day of ICU discharge if before day 14]

    samples taken on D7 and D14 or the day of discharge from intensive care unit if before D14

  17. Proportion of active smoker or active vapers or taking nicotine substitutes documented by examination [2 weeks after treatment decrease, 8 weeks after treatment decrease]

  18. Proportion of active smoker or active vapers or taking nicotine substitutes documented by urinary cotinine [2 weeks after treatment decrease, 8 weeks after treatment decrease]

  19. Mean score of Desire to smoke defined by French Tobacco Craving scale [2 weeks after treatment decrease, 8 weeks after treatment decrease]

  20. Mean score of Withdrawal symptoms scale [2 weeks after treatment decrease, 8 weeks after treatment decrease]

  21. Mean score of Hospital anxiety and depression scale [2 weeks after treatment decrease, 8 weeks after treatment decrease]

  22. Post traumatic stress disorder scale [2 weeks after treatment decrease, 8 weeks after treatment decrease]

  23. Mean score of Insomnia severity scale [2 weeks after treatment decrease]

  24. Cotinin rate in blood [8 weeks after treatment decrease]

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
  1. Patient ≥ 18 years

  2. Documented diagnosis of COVID 19 (according to the tests referenced on the list published on the website : https://covid-19.sante.gouv.fr.tests)

  3. Hospitalized in intensive care unit, intubated and mechanically ventilated for less than 48 hours

  4. Non-smoker and non-vaping or abstinent patient for at least 12 months

  5. 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.

  6. Affiliated to a social security scheme or beneficiary of such a scheme (AME excluded)

Exclusion Criteria:
  1. Chronic respiratory failure defined by PaCO2> 60 mmHg in ambulatory patients (respiratory parameters at baseline).

  2. Mechanical ventilation at home (non-invasive mechanical ventilation or via a tracheostomy) with the exception of CPAP / BIPAP used only for sleep apnea syndromes

  3. Predictable mechanical ventilation duration <48 hours

  4. Moribund patient or death expected on the day of randomization, or with a SAPS II score> 90

  5. Cerebral deficiency with dilated areactive pupils or irreversible neurological pathology.

  6. Other concomitant severe pathology with an estimated life expectancy of less than 1 year

  7. Treatment with nicotine replacement therapy or varenicline or bupropion ongoing

  8. 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)

  • Known severe heart failure (Defined, for this study, by systolic LV dysfunction with an LV ejection fraction (LVEF) of less than 30%)

  • Severe renal failure (Defined by KDIGO stage 3)

  • Severe hepatic impairment (Defined by a factor V <30%)

  • Arteriopathy obliterating of the lower limbs stage III and IV

  • Uncontrolled hyperthyroidism

  • Gastroduodenal esophagitis or ulcer undergoing treatment or active

  1. Patient under guardianship or curatorship

  2. Patient deprived of liberty by judicial or administrative decision

  3. Patient included in another interventional trial evaluating a health product

Contacts and Locations

Locations

Site City State Country Postal Code
1 Centre Hospitalier Victor Dupouy - Service de Réanimation polyvalente et USC Argenteuil France 95100
2 CHRU de Besançon - Service de Médecine Intensive Réanimation Besançon France 25030
3 Centre Hospitalier Sud Francilien - Service de réanimation Corbeil-Essonnes France 91100
4 CHU Dijon - Hôpital François Miterrand Service de Médecine Intensive Réanimation Dijon France 22033
5 Hôpital Simone VEIL - Service d'Anesthésie-Réanimation Eaubonne France 95000
6 Grand Hôpital de l'Est Francilien - Site Jossigny - Réanimation Jossigny France 77600
7 Hôpital Bicêtre - Service de Médecine Intensive Réanimation Le Kremlin-Bicêtre France 94270
8 Grand Hôpital de l'Est Francilien Site Meaux - Service de Réanimation Médico-Chirurgicale Meaux France 77104
9 Groupement Hospitalier de la Région de Mulhouse Sud Alsace - Hop Emile MULLER Mulhouse France 68100
10 CHU Nice - Hôpital L'Archet 1 - Service de Médecine Intensive Réanimation Nice France 06000
11 CHR Orléans Service de Médecine Intensive Réanimation Orléans France 45067
12 Hôpital Pitié Salpêtrière - ICU Paris France 75013
13 Hôpital Pitié Salpêtrière - Intensive care unit Paris France 75013
14 Institut Mutualiste Montsouris Service de Réanimation Polyvalente Paris France 75014
15 Hôpital Tenon - Service de Médecine Intensive Réanimation Paris France 75020
16 Centre Hospitalier René Dubos - Service de Réanimation Médico-Chirurgicale Pontoise France 95303
17 Hôpital DELAFONTAINE Service de Médecine Intensive Réanimation Saint-Denis France 93200
18 Médipôle Hôpital Privé - MHP Service de Médecine Intensive Réanimation Villeurbanne France 69100

Sponsors and Collaborators

  • Assistance Publique - Hôpitaux de Paris

Investigators

  • Principal Investigator: Alain COMBES, MD, Assistance Publique - Hôpitaux de Paris

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier:
NCT04598594
Other Study ID Numbers:
  • APHP200537
  • 2020-003723-42
First Posted:
Oct 22, 2020
Last Update Posted:
Jun 22, 2021
Last Verified:
Jun 1, 2021
Studies a U.S. FDA-regulated Drug Product:
No
Studies a U.S. FDA-regulated Device Product:
No
Keywords provided by Assistance Publique - Hôpitaux de Paris
Additional relevant MeSH terms:

Study Results

No Results Posted as of Jun 22, 2021