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

Sponsor

Assistance Publique - Hôpitaux de Paris (Other)

Overall Status

Unknown status

CT.gov ID

NCT04355429

Collaborator

(none)

230

Enrollment

Locations

Arms

2.9

Anticipated Duration (Months)

20.9

Patients Per Site

7.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Pneumonia Coronavirus Infection COVID-19	Drug: captopril 25mg	Phase 2

Detailed 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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

230 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Efficacy of Captopril Nebulization in Covid-19 Patients Suffering of SARS CoV-2 Pneumonia. A Randomized Phase II Study

Anticipated Study Start Date :

May 5, 2020

Anticipated Primary Completion Date :

Jul 1, 2020

Anticipated Study Completion Date :

Aug 1, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: CAPTOPROL Inhalation administration by nebulization	Drug: captopril 25mg Drug administration Other Names: Any
No Intervention: STANDARS CARE According to surviving covid-Campaign guidelines

Arm

Intervention/Treatment

Experimental: CAPTOPROL

Inhalation administration by nebulization

Drug: captopril 25mg

Drug administration

Other Names:

Any

No Intervention: STANDARS CARE

According to surviving covid-Campaign guidelines

Outcome Measures

Primary Outcome Measures

Efficacy of captopril nebulization addition to standard of care compared to standard of care. [14 Days]
To assess determine the efficacy of captopril nebulization addition to standard of care compared to standard of care in term of 14-day ventilation free survival

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts 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

Contacts and Locations

Locations

	Site	City	Country	Postal Code
1	CH Victor Dupuy- Argenteuil	Argenteuil	France
2	Hôpital Avicenne,	Bobigny	France	93000
3	Hôpital Avicenne	Bobigny	France	93000
4	Hôpital Avicenne	Bobigny	France
5	Hôpital Antoine Béclère	Clamart	France
6	CH de Compiègne-Noyon	Compiègne	France
7	Groupe hospitalier Sud Ile de France	Melun	France
8	Hôpital de la Pitié- Salpêtrière	Paris	France
9	Hôpital Tenon	Paris	France
10	CHRU de Tours, Hôpital Bretonneau	Tours	France
11	Hôpital de Tours	Tours	France