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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| CAPTOPROL | Experimental | Inhalation administration by nebulization |
|
| STANDARS CARE | No Intervention | According to surviving covid-Campaign guidelines |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| captopril 25mg | Drug | Drug administration |
|
|
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Mohammed RAHAOUI, PM | Contact | +33 1 48 95 59 77 | mohammed.rahaoui@aphp.fr | |
| Yacine TANDJAOUI-LAMBIOTTE, MD | Contact | yacine.tandjaoui-lambiotte@aphp.fr |
| Name | Affiliation | Role |
|---|---|---|
| Yacine TANDJAOUI-LAMBIOTTE, MD | Assistance Publique - Hôpitaux de Paris | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| CH Victor Dupuy- Argenteuil | Argenteuil | France |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 32129518 | Background | 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. | |
| 32109013 | Result | 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. |
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| Hôpital Avicenne, | Bobigny | 93000 | France |
|
| Hôpital Avicenne | Bobigny | 93000 | 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 |
|
| 16166518 | Result | 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. |
| 16001071 | Result | 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. |
| 32125455 | Result | 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. |
| ID | Term |
|---|---|
| D011014 | Pneumonia |
| D018352 | Coronavirus Infections |
| D000086382 | COVID-19 |
| ID | Term |
|---|---|
| D012141 | Respiratory Tract Infections |
| D007239 | Infections |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
| D003333 | Coronaviridae Infections |
| D030341 | Nidovirales Infections |
| D012327 | RNA Virus Infections |
| D014777 | Virus Diseases |
| D011024 | Pneumonia, Viral |
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| ID | Term |
|---|---|
| D002216 | Captopril |
| ID | Term |
|---|---|
| D011392 | Proline |
| D007098 | Imino Acids |
| D000598 | Amino Acids, Cyclic |
| D000596 | Amino Acids |
| D000602 | Amino Acids, Peptides, and Proteins |
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