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

COVID-19 Clinical Trial

— CAPTOCOVID  

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT04355429
• Other study ID #: APHP200410
• Status: Not yet recruiting
• Phase: Phase 2
• Start date: May 5, 2020
• Est. completion date: August 2020

Study information

• Verified date: April 2020
• Source: Assistance Publique - Hôpitaux de Paris
• Contact: Mohammed RAHAOUI, PM
• Phone: +33 1 48 95 59 77
• Email: mohammed.rahaoui[@]aphp.fr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 230
• Est. completion date: August 2020
• Est. primary completion date: July 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Hospitalization for acute respiratory failure requiring oxygen administration =3L/mn

2. Age > 18 years or older

3. Presence of pneumonia

4. PCR SARS-CoV-2 positive in any biological sample in the last 7 days

5. Patient affiliated to social security regime

6. 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:

1. Decision of withholding invasive mechanical ventilation

2. Shock requiring vasopressor infusion

3. Co-infection with another respiratory pathogen which could be responsible of pneumonia

4. Hypersensitivity to captopril, to any other angiotensin converting enzyme inhibitor or any of the excipients of the specialty used

5. History of angio-oedema

6. History of ACE-inhibitor allergy

7. 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.

8. Patient who is currently enrolled in other investigational study;

9. Persons deprived of their liberty by judicial or administrative decision,

10. Persons under legal protection/safeguard of justice,

11. Patients under duress psychiatric care,

12. Persons admitted to a health or social institution

13. Patient on state medical aid

Related Conditions & MeSH terms

• Coronavirus Infection
• Coronavirus Infections
• COVID-19
• Pneumonia
• Severe Acute Respiratory Syndrome

Intervention

Drug:
• captopril 25mg
Drug administration

Locations

Country	Name	City	State
France	CH Victor Dupuy- Argenteuil	Argenteuil
France	Hôpital Avicenne	Bobigny
France	Hôpital Avicenne	Bobigny
France	Hôpital Avicenne,	Bobigny
France	Hôpital Antoine Béclère	Clamart
France	CH de Compiègne-Noyon	Compiègne
France	Groupe hospitalier Sud Ile de France	Melun
France	Hôpital de la Pitié- Salpêtrière	Paris
France	Hôpital Tenon	Paris
France	CHRU de Tours, Hôpital Bretonneau	Tours
France	Hôpital de Tours	Tours

Sponsors (1)

Lead Sponsor	Collaborator
Assistance Publique - Hôpitaux de Paris

Country where clinical trial is conducted

France, 

References & Publications (5)

Guan WJ, Ni ZY, Hu Y, Liang WH, Ou CQ, He JX, Liu L, Shan H, Lei CL, Hui DSC, Du B, Li LJ, Zeng G, Yuen KY, Chen RC, Tang CL, Wang T, Chen PY, Xiang J, Li SY, Wang JL, Liang ZJ, Peng YX, Wei L, Liu Y, Hu YH, Peng P, Wang JM, Liu JY, Chen Z, Li G, Zheng ZJ — View Citation

Gurwitz D. Angiotensin receptor blockers as tentative SARS-CoV-2 therapeutics. Drug Dev Res. 2020 Mar 4. doi: 10.1002/ddr.21656. [Epub ahead of print] — View Citation

Imai Y, Kuba K, Rao S, Huan Y, Guo F, Guan B, Yang P, Sarao R, Wada T, Leong-Poi H, Crackower MA, Fukamizu A, Hui CC, Hein L, Uhlig S, Slutsky AS, Jiang C, Penninger JM. Angiotensin-converting enzyme 2 protects from severe acute lung failure. Nature. 2005 — View Citation

Li F, Li W, Farzan M, Harrison SC. Structure of SARS coronavirus spike receptor-binding domain complexed with receptor. Science. 2005 Sep 16;309(5742):1864-8. — View Citation

Zhang H, Penninger JM, Li Y, Zhong N, Slutsky AS. Angiotensin-converting enzyme 2 (ACE2) as a SARS-CoV-2 receptor: molecular mechanisms and potential therapeutic target. Intensive Care Med. 2020 Apr;46(4):586-590. doi: 10.1007/s00134-020-05985-9. Epub 202 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Efficacy of captopril nebulization addition to standard of care compared to standard of care.	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	14 Days