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

NCT ID: NCT04355429

Last Updated: 2020-04-28

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2
• Total Enrollment: 230 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-05-05
• Study Completion Date: 2020-08-31

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.

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.

Conditions

Pneumonia; Coronavirus Infection; COVID-19

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

CAPTOPROL

Inhalation administration by nebulization

Group Type: EXPERIMENTAL

captopril 25mg

Intervention Type: DRUG

Drug administration

STANDARS CARE

According to surviving covid-Campaign guidelines

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

captopril 25mg

Drug administration

Intervention Type: DRUG

Other Intervention Names

Any

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Assistance Publique - Hôpitaux de Paris

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Yacine TANDJAOUI-LAMBIOTTE, MD

Role: PRINCIPAL_INVESTIGATOR

Assistance Publique - Hôpitaux de Paris

Locations

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, , France

Countries

France

Central Contacts

Mohammed RAHAOUI, PM

Role: CONTACT

mohammed.rahaoui@aphp.fr

+33 1 48 95 59 77

Yacine TANDJAOUI-LAMBIOTTE, MD

Role: CONTACT

yacine.tandjaoui-lambiotte@aphp.fr

Facility Contacts

Pascale LONGUET, MD

Role: primary

Olivier BOUCHAUD, Pr

Role: primary

Yacine TANDJAOUI-LAMBIOTTE, MD

Role: primary

yacine.tandjaoui-lambiotte@aphp.fr

Nunes HILARIO, MD

Role: primary

Anne-Lise LECAPITAINE, MD

Role: primary

Sylvain DIAMANTIS, MD

Role: primary

Alexandre BLEIBTREU, MD

Role: primary

Gilles PIALOUX, Pr

Role: primary

Louis BERNARD, MD

Role: primary

Laurent PLANTIER, Pr

Role: primary

References

Gurwitz D. Angiotensin receptor blockers as tentative SARS-CoV-2 therapeutics. Drug Dev Res. 2020 Aug;81(5):537-540. doi: 10.1002/ddr.21656. Epub 2020 Mar 4.

Reference Type: BACKGROUND

PMID: 32129518 (View on PubMed)

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, Qiu SQ, Luo J, Ye CJ, Zhu SY, Zhong NS; China Medical Treatment Expert Group for Covid-19. Clinical Characteristics of Coronavirus Disease 2019 in China. N Engl J Med. 2020 Apr 30;382(18):1708-1720. doi: 10.1056/NEJMoa2002032. Epub 2020 Feb 28.

Reference Type: RESULT

PMID: 32109013 (View on PubMed)

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. doi: 10.1126/science.1116480.

Reference Type: RESULT

PMID: 16166518 (View on PubMed)

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 Jul 7;436(7047):112-6. doi: 10.1038/nature03712.

Reference Type: RESULT

PMID: 16001071 (View on PubMed)

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 2020 Mar 3. No abstract available.

Reference Type: RESULT

PMID: 32125455 (View on PubMed)

Other Identifiers

APHP200410

Identifier Type: -

Identifier Source: org_study_id