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

Assistance Publique - Hôpitaux de Paris

Status and phase: Completed; Phase 3

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

Treatments: Drug: Patch, Nicotine; Drug: Patch, Placebo

Study type: Interventional

Funder types: Other

Identifiers

NCT04598594

APHP200537

2020-003723-42 (EudraCT Number)

Details and patient eligibility

About

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.

Enrollment: 220 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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220 participants in 2 patient groups, including a placebo group

Nicotine patch

Experimental group

Treatment:

Drug: Patch, Nicotine

Placebo patch

Placebo Comparator group

Treatment:

Drug: Patch, Placebo