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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04598594
Recruitment Status : Completed
First Posted : October 22, 2020
Last Update Posted : June 22, 2021
Sponsor:
Information provided by (Responsible Party):
Assistance Publique - Hôpitaux de Paris

Tracking Information
First Submitted Date  ICMJE October 15, 2020
First Posted Date  ICMJE October 22, 2020
Last Update Posted Date June 22, 2021
Actual Study Start Date  ICMJE November 6, 2020
Actual Primary Completion Date April 29, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 21, 2020)
Mortality [ Time Frame: Day 28 ]
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: October 21, 2020)
  • Mortality [ Time Frame: Day 60 ]
  • Time before successful extubation [ Time Frame: 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).
  • Number of days living without invasive mechanical ventilation [ Time Frame: Day 28 ]
  • Composite score incorporating death and the number of days living without mechanical ventilation [ Time Frame: 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
  • Mean evolution of blood gases [ Time Frame: Day 1 to Day 14 ]
    measured each day from day 1 to day 14
  • Mean evolution of Tidal Volume (ventilator parameters) [ Time Frame: Day 1 to Day 14 ]
    measured each day from day 1 to day 14
  • Mean evolution of respiratory rate (ventilator parameters) [ Time Frame: Day 1 to Day 14 ]
    measured each day from day 1 to day 14
  • Mean evolution of Positive Expiratory Pressure (ventilator parameters) [ Time Frame: Day 1 to Day 14 ]
    measured each day from day 1 to day 14
  • Mean evolution of plateau pressure (ventilator parameters) [ Time Frame: Day 1 to Day 14 ]
    measured each day from day 1 to day 14
  • Mean evolution of fraction of inspired oxygen (ventilator parameters) [ Time Frame: Day 1 to Day 14 ]
    measured each day from day 1 to day 14
  • Evolution of the Sequential Organ Failure Assessment (SOFA) score and its components by organ [ Time Frame: Day 1 to Day 28 ]
    A higher score indicate a worse outcome
  • Number of days alive without organ failure [ Time Frame: Day 28, day 60 ]
  • Duration of hospitalization in intensive care unit [ Time Frame: From day 1 up to 3 months ]
  • Duration of hospitalization in hospital [ Time Frame: From day 1 up to 3 months ]
  • Number of days alive and out of the ICU and hospital [ Time Frame: Day 28, day 60 ]
  • Evolution of viral load [ Time Frame: 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
  • Proportion of active smoker or active vapers or taking nicotine substitutes documented by examination [ Time Frame: 2 weeks after treatment decrease, 8 weeks after treatment decrease ]
  • Proportion of active smoker or active vapers or taking nicotine substitutes documented by urinary cotinine [ Time Frame: 2 weeks after treatment decrease, 8 weeks after treatment decrease ]
  • Mean score of Desire to smoke defined by French Tobacco Craving scale [ Time Frame: 2 weeks after treatment decrease, 8 weeks after treatment decrease ]
  • Mean score of Withdrawal symptoms scale [ Time Frame: 2 weeks after treatment decrease, 8 weeks after treatment decrease ]
  • Mean score of Hospital anxiety and depression scale [ Time Frame: 2 weeks after treatment decrease, 8 weeks after treatment decrease ]
  • Post traumatic stress disorder scale [ Time Frame: 2 weeks after treatment decrease, 8 weeks after treatment decrease ]
  • Mean score of Insomnia severity scale [ Time Frame: 2 weeks after treatment decrease ]
  • Cotinin rate in blood [ Time Frame: 8 weeks after treatment decrease ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Evaluation of the Efficacy of Nicotine Patches in SARS-CoV2 (COVID-19) Infection in Intensive Care Unit Patients
Official Title  ICMJE Evaluation of the Efficacy of Nicotine Patches in SARS-CoV2 (COVID-19) Infection in Intensive Care Unit Patients
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.

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Condition  ICMJE
  • Covid19
  • SARS-Associated Coronavirus as Cause of Disease Classified Elsewhere
Intervention  ICMJE
  • 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
  • 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
Study Arms  ICMJE
  • Experimental: Nicotine patch
    Intervention: Drug: Patch, Nicotine
  • Placebo Comparator: Placebo patch
    Intervention: Drug: Patch, Placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: October 21, 2020)
220
Original Estimated Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE June 20, 2021
Actual Primary Completion Date April 29, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
  9. Patient under guardianship or curatorship
  10. Patient deprived of liberty by judicial or administrative decision
  11. Patient included in another interventional trial evaluating a health product
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE France
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04598594
Other Study ID Numbers  ICMJE APHP200537
2020-003723-42 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Assistance Publique - Hôpitaux de Paris
Study Sponsor  ICMJE Assistance Publique - Hôpitaux de Paris
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Alain COMBES, MD Assistance Publique - Hôpitaux de Paris
PRS Account Assistance Publique - Hôpitaux de Paris
Verification Date June 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP