Efficacy of Nicotine in Preventing COVID-19 Infection (NICOVID-PREV)

• ClinicalTrials.gov Identifier: NCT04583410
• Recruitment Status: Unknown
• First Posted: October 12, 2020
• Last Update Posted: February 17, 2021
• Sponsor: Assistance Publique - Hôpitaux de Paris
• Information provided by (Responsible Party): Assistance Publique - Hôpitaux de Paris

Tracking Information

• First Submitted Date: September 28, 2020
• First Posted Date: October 12, 2020
• Last Update Posted Date: February 17, 2021
• Actual Study Start Date: October 22, 2020
• Estimated Primary Completion Date: December 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: February 15, 2021)

SARS-COV2 seroconversion between W0 and W19 after randomization [ Time Frame: Between week 0 and week 19 ]

This is the proportion of subjects with at least one positive serology between W2 and W19. The time of S19 takes into account a seroconversion delay of 5 weeks in relation to the SARS-CoV2 contamination.

Original Primary Outcome Measures (submitted: October 9, 2020)

SARS-COV2 seroconversion between W0 and W19 after randomization [ Time Frame: Between week 0 and week 19 ]

This is the proportion of patients with at least one positive serology between W2 and W19. The time of S19 takes into account a seroconversion delay of 5 weeks in relation to the SARS-CoV2 contamination.

Current Secondary Outcome Measures (submitted: October 9, 2020)

• Proportion of documented symptomatic COVID-19 infection [ Time Frame: Week 8, Week16 ]
• SARS-COV2 seroconversion [ Time Frame: Week 16 ]
  This is the proportion of patients with at least one positive serology between W2 and W16.
• Asymptomatic COVID-19 infection proportion at week 14 [ Time Frame: Week 14 ]
  Asymptomatic COVID-19 infection is defined as SARS-CoV2 seroconversion at Week 19 without symptoms suggestive of COVID until the end of Week 16 to take in account of the two weeks of incubation period
• Proportion of severe COVID-19 infection [ Time Frame: Week 8, Week16 ]
  documented infection (positive SARS-CoV2 PCR test and / or suggestive chest CT scan and / or seroconversion) whose first symptoms appeared before W8 and W16 respectively, and requiring hospitalization or home oxygen therapy, or having resulted in death
• Number of sick leaves for a COVID-19 infection [ Time Frame: Week 16 ]
• Number of days off during sick leaves for a COVID-19 infection [ Time Frame: Week 16 ]
• Proportion of AE, SAE [ Time Frame: From inclusion and week 25 ]
• Intensity and frequency of nausea, dizziness, feeling of empty head, headache, vomiting [ Time Frame: Week 25 ]
• Proportion of active smoker or active vapers or taking nicotine substitutes documented by examination [ Time Frame: Week 25 ]
• Proportion of active smoker or active vapers or taking nicotine substitutes documented by urinary cotinine [ Time Frame: Week 25 ]
• Mean score of Desire to smoke defined by French Tobacco Craving scale [ Time Frame: Week 25 ]
• Mean score of Withdrawal symptoms scale [ Time Frame: Week 25 ]
• Dosage of cotinine in the urine [ Time Frame: Week 8 and 25 ]
• Mean score of Fatigue Numeric rating scale [ Time Frame: Week 2, week 8, week 16 ]
• Weight [ Time Frame: Week 8, week 16, week 25 ]
• Mean score of Hospital anxiety and depression scale [ Time Frame: Week 2, week 8, week 16 ]
• Mean score of Insomnia severity scale [ Time Frame: Week 2, week 8, week 16 ]
• Positive and negative syndrome scale [ Time Frame: Week 2, week 8, week 16 ]

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Efficacy of Nicotine in Preventing COVID-19 Infection
• Official Title: Efficacy of Nicotine in Preventing COVID-19 Infection

Brief Summary

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.

According to current knowledge, there are no treatments that prevent the spread of the infection, especially in exposed populations, or the disease progression to a severe form.

Daily active smokers are infrequent among outpatients or hospitalized patients with COVID-19. Several arguments suggest that nicotine is responsible for this protective effect via the nicotinic acetylcholine receptor (nAChR).

Nicotine may inhibit the penetration and spread of the virus and have a prophylactic effect in COVID-19 infection.

However, the epidemic is progressing throughout French territory and new variants (in particular the "English B1. 1.7 variant of SARS-COV-2") much more contagious run a risk of accelerating the epidemic in the population. The anti-SARS-COV-2 vaccines recently launched (or being evaluated) represent great hope in this health crisis, but trials were only able to show their effectiveness on symptomatic forms of SARS-COV-2 infection. On the one hand, the vaccination compaign for the entire population requires many months,which leaves many unprotected subjects waiting. In addition, there is currently no evidence of a protective role of vaccines against asymptomatic forms of COVID-19 and therefore on SARS-COV-2 transmission. Finally, the nicotine patches may protect people in hight-risk areas/periods until they are vaccinated (if they accept it and are eligible for it) and in the post-vaccination weeks necessary for the effectiveness of the vaccine,which reinforces the importance of evaluating this alternative prevention strategy, in the context of the arrival of vaccines

• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment

Condition

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

Intervention

• Drug: Nicotine patch

  NICOPATCHLIB, 7mg/24h Day 1 to day 3 : 3,5 mg/day Day 4 to day 9 : 7 mg/day Day 10 to Day 15 : 10,5 mg/day Day 16 to day 98 : 14 mg/day

  Decrease treatment Day 99 to day 105 : 10,5 mg/day Day 106 to day 112 : 7 mg/day Day 113 to Day 119 : 3,5 mg/day

• Drug: Placebo patch

  PLACEBO OF NICOPATCHLIB, 7mg/24h Day 1 to day 3 : 3,5 mg/day Day 4 to day 9 : 7 mg/day Day 10 to Day 15 : 10,5 mg/day Day 16 to day 98 : 14 mg/day

  Decrease treatment Day 99 to day 105 : 10,5 mg/day Day 106 to day 112 : 7 mg/day Day 113 to Day 119 : 3,5 mg/day

Study Arms

• Experimental: Nicotine patch
  Intervention: Drug: Nicotine patch
• Placebo Comparator: Placebo patch
  Intervention: Drug: Placebo patch

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Unknown status
• Estimated Enrollment (submitted: October 9, 2020): 1633
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: June 2022
• Estimated Primary Completion Date: December 2021 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

1. Aged 18 or over
2. May be followed for the duration of the study
3. Obtaining free, informed and signed consent
4. Affiliated to a social security scheme or beneficiary of such a scheme (except AME)
5. Non-smoker and non-vaping (for former smokers or vapers: abstinent for at least 12 months)

Exclusion Criteria:

1. Symptoms suggestive of COVID-19 on the day of inclusion or in the past 14 days
2. Documented history of COVID-19 and / or positive SARS-COV2 serology before the day of inclusion
3. Treatment ongoing with nicotine replacement therapy, varenicline or bupropion within 30 days before inclusion
4. Known addiction problem to alcohol (defined by AUDIT-C > or = 10) or other substances.
5. Vaccinated against COVID19 infection.

6. Contraindications for nicotine patches:

   • pregnant woman (negative pregnancy test on inclusion) or breastfeeding woman
   • lack of effective contraception for women of childbearing potential
   • Generalized skin conditions that can 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 angor
   • Severe cardiac arrhythmia (defined by wearing an automatic implantable defibrillator)
   • Obliterating peripheral arterial disease
   • Known severe heart failure
   • Known severe renal or hepatic impairment,
   • Pheochromocytoma
   • Uncontrolled hyperthyroidism

   • Esophagitis due to gastroesophageal reflux disease or active peptic ulcer

     7 Already included in an interventional trial evaluating a health product 8 Staff under guardianship or curatorship or deprived of their liberty by a judicial or administrative decision 9 Do not have a smartphone

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: France

Administrative Information

• NCT Number: NCT04583410
• Other Study ID Numbers: APHP200538; 2020-003722-23 ( 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: Not Provided
• Current Responsible Party: Assistance Publique - Hôpitaux de Paris
• Original Responsible Party: Same as current
• Current Study Sponsor: Assistance Publique - Hôpitaux de Paris
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Principal Investigator: Zahir AMOURA, MD; Assistance Publique - Hôpitaux de Paris

• PRS Account: Assistance Publique - Hôpitaux de Paris
• Verification Date: February 2021