Efficacy of Captopril in Covid-19 Patients With Severe Acute Respiratory Syndrome (SARS) CoV-2 Pneumonia (CAPTOCOVID)

Assistance Publique - Hôpitaux de Paris

Status and phase

Unknown

Phase 2

Conditions

COVID-19

Pneumonia

Coronavirus Infection

Treatments

Drug: captopril 25mg

Study type

Interventional

Funder types

Other

Identifiers

NCT04355429

APHP200410

Details and patient eligibility

About

Captopril being an effective drug available in liquid preparation, administration by nebulization could be of interest for maximizing lung action and minimizing systemic side effects. Such a treatment might be used for "Covid-19" patients with pneumonia in order to avoid ARDS.

Full description

Coronavirus Disease 2019 (COVID-19) is due to SARS-CoV-2 infection. The main cause of death is refractory acute respiratory distress syndrome (ARDS) secondary to SARS-CoV-2 pneumonia. The SARS-CoV-2 may have specific virulence factors to achieve mortality rates around 3%. As the SARS-CoV, virus responsible of the Severe Acute Respiratory Syndrome in 2003 (which mortality was around 10%), the SARS-CoV-2 uses angiotensin-converting enzyme 2 (ACE2) as the receptor binding domain for its spike protein making ACE2 the gateway in the alveolar epithelial cells1. Angiotensin-converting enzyme (ACE) and ACE2 are known to be present in respiratory epithelium and to have antagonist physiological functions. ACE2 has an anti-inflammatory, anti-fibrosing role, anti-oxydant and vasodilatator activity, while ACE has the opposite characteristics. These two enzymes have a negative control on each other, one inhibiting the other. Demonstrated that SARS-CoV is responsible of a downregulation of ACE2 functions by using ACE2 as cell receptor2. While ACE2 is downregulated, ACE activity increase leading to more alveolar damage and acute respiratory failure.

ACE inhibitors are common drugs used to treat hypertension worldwide. Using an ACE inhibitor as treatment against SARS-CoV-2 could be counter-intuitive because increasing ACE2 expression would open the cellular gate to the virus3,4. However, ACE2 was described as protecting lung injury2, leading Recombinant Human ACE2 as a perspective for SARS-CoV-2 treatment.

A simple way to increase ACE2 in patients with SARS-CoV-2 pneumonia could be an inhalation of ACE inhibitor.

Enrollment

230 estimated patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Hospitalization for acute respiratory failure requiring oxygen administration ≥3L/mn
Age > 18 years or older
Presence of pneumonia
PCR SARS-CoV-2 positive in any biological sample in the last 7 days
Patient affiliated to social security regime
Written informed consent provided by the patient or alternatively by next-of-kin, or in emergency situations, prior to any protocol-specific procedures

Exclusion criteria

Decision of withholding invasive mechanical ventilation
Shock requiring vasopressor infusion
Co-infection with another respiratory pathogen which could be responsible of pneumonia
Hypersensitivity to captopril, to any other angiotensin converting enzyme inhibitor or any of the excipients of the specialty used
History of angio-oedema
History of ACE-inhibitor allergy
Known pregnancy or current lactation: Female subject of childbearing potential should have a negative serum pregnancy test prior to receiving the first dose of study medication.
Patient who is currently enrolled in other investigational study;
Persons deprived of their liberty by judicial or administrative decision,
Persons under legal protection/safeguard of justice,
Patients under duress psychiatric care,
Persons admitted to a health or social institution
Patient on state medical aid