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Covid19Phase 3NICOVID-REANCT04598594

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

A Phase 3 study testing Patch, Nicotine in people with Covid19 and SARS-Associated Coronavirus as Cause of Disease Classified Elsewhere, run by Assistance Publique - Hôpitaux de Paris at 18 sites in France.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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). Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Patch, Nicotine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
220 participants
Where
18 sitesFrance
Study dates
6 Nov 2020to 20 Jun 2021
Phase
Phase 3
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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)

Who cannot join

  • 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
Show all 24Show fewer
  • 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)
  • 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
  • Patient under guardianship or curatorship
  • Patient deprived of liberty by judicial or administrative decision
  • Patient included in another interventional trial evaluating a health product

Trial locations and contacts

18 sites in 1 country.

18 sites in 1 country

France18 sites

  • Centre Hospitalier Victor Dupouy - Service de Réanimation polyvalente et USC

    Argenteuil, 95100

  • CHRU de Besançon - Service de Médecine Intensive Réanimation

    Besançon, 25030

  • Centre Hospitalier Sud Francilien - Service de réanimation

    Corbeil-Essonnes, 91100

  • CHU Dijon - Hôpital François Miterrand Service de Médecine Intensive Réanimation

    Dijon, 22033

  • Hôpital Simone VEIL - Service d'Anesthésie-Réanimation

    Eaubonne, 95000

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

    Jossigny, 77600

  • Hôpital Bicêtre - Service de Médecine Intensive Réanimation

    Le Kremlin-Bicêtre, 94270

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

    Meaux, 77104

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

    Mulhouse, 68100

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

    Nice, 06000

  • CHR Orléans Service de Médecine Intensive Réanimation

    Orléans, 45067

  • Hôpital Pitié Salpêtrière - ICU

    Paris, 75013

  • Hôpital Pitié Salpêtrière - Intensive care unit

    Paris, 75013

  • Institut Mutualiste Montsouris Service de Réanimation Polyvalente

    Paris, 75014

  • Hôpital Tenon - Service de Médecine Intensive Réanimation

    Paris, 75020

  • Centre Hospitalier René Dubos - Service de Réanimation Médico-Chirurgicale

    Pontoise, 95303

  • Hôpital DELAFONTAINE Service de Médecine Intensive Réanimation

    Saint-Denis, 93200

  • Médipôle Hôpital Privé - MHP Service de Médecine Intensive Réanimation

    Villeurbanne, 69100

Other trials in France

About this study

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.

Being tested
Patch, Nicotine, Patch, Placebo
Keywords
Covid19, SARS-CoV2, Mechanical ventilation, ICU, Nicotine
Medical subject headings
COVID-19

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Patch, NicotineDrug

    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

  • Patch, PlaceboDrug

    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

Study groups in NCT04598594
Study groupRoleWhat they receive
Nicotine patchExperimentalNot described
Receives: Drug: Patch, Nicotine
Placebo patchPlacebo comparatorNot described
Receives: Drug: Patch, Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Mortality

    Measured: Day 28

Secondary outcomes (24)

  1. Mortality

    Measured: Day 60

  2. Time before successful extubation

    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).

    Measured: Day 60

  3. Number of days living without invasive mechanical ventilation

    Measured: Day 28

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

    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

    Measured: Day 60

  5. Mean evolution of blood gases

    measured each day from day 1 to day 14

    Measured: Day 1 to Day 14

  6. Mean evolution of Tidal Volume (ventilator parameters)

    measured each day from day 1 to day 14

    Measured: Day 1 to Day 14

  7. Mean evolution of respiratory rate (ventilator parameters)

    measured each day from day 1 to day 14

    Measured: Day 1 to Day 14

  8. Mean evolution of Positive Expiratory Pressure (ventilator parameters)

    measured each day from day 1 to day 14

    Measured: Day 1 to Day 14

  9. Mean evolution of plateau pressure (ventilator parameters)

    measured each day from day 1 to day 14

    Measured: Day 1 to Day 14

  10. Mean evolution of fraction of inspired oxygen (ventilator parameters)

    measured each day from day 1 to day 14

    Measured: Day 1 to Day 14

  11. Evolution of the Sequential Organ Failure Assessment (SOFA) score and its components by organ

    A higher score indicate a worse outcome

    Measured: Day 1 to Day 28

  12. Number of days alive without organ failure

    Measured: Day 28, day 60

  13. Duration of hospitalization in intensive care unit

    Measured: From day 1 up to 3 months

  14. Duration of hospitalization in hospital

    Measured: From day 1 up to 3 months

  15. Number of days alive and out of the ICU and hospital

    Measured: Day 28, day 60

  16. Evolution of viral load

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

    Measured: Day 7, Day 14 or day of ICU discharge if before day 14

  17. Proportion of active smoker or active vapers or taking nicotine substitutes documented by examination

    Measured: 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

    Measured: 2 weeks after treatment decrease, 8 weeks after treatment decrease

  19. Mean score of Desire to smoke defined by French Tobacco Craving scale

    Measured: 2 weeks after treatment decrease, 8 weeks after treatment decrease

  20. Mean score of Withdrawal symptoms scale

    Measured: 2 weeks after treatment decrease, 8 weeks after treatment decrease

  21. Mean score of Hospital anxiety and depression scale

    Measured: 2 weeks after treatment decrease, 8 weeks after treatment decrease

  22. Post traumatic stress disorder scale

    Measured: 2 weeks after treatment decrease, 8 weeks after treatment decrease

  23. Mean score of Insomnia severity scale

    Measured: 2 weeks after treatment decrease

  24. Cotinin rate in blood

    Measured: 8 weeks after treatment decrease

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted22 Oct 2020
  2. Study start6 Nov 2020
  3. Primary completion29 Apr 2021
  4. Study completion20 Jun 2021

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
220 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04598594
Sponsor's protocol ID
APHP200537
Other IDs
2020-003723-42
Acronym
NICOVID-REA
Status last verified
Jun 2021
First submitted
15 Oct 2020
Last updated
22 Jun 2021
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No

Publications

  • 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.

    PubMed 35676335

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Patch, Nicotine in people with Covid19 and SARS-Associated Coronavirus as Cause of Disease Classified Elsewhere, run by Assistance Publique - Hôpitaux de Paris at 18 sites in France.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 24 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 22 Jun 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 18 sites in France. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Mortality (time frame: Day 28). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04598594, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Jun 2021.

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