Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT05418361 |
| Other study ID # |
FAMASU/2021 |
| Secondary ID |
|
| Status |
Completed |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
June 15, 2021 |
| Est. completion date |
February 20, 2022 |
Study information
| Verified date |
June 2022 |
| Source |
Ain Shams University |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational
|
Clinical Trial Summary
Blockage of renin-angiotensin-aldosterone system (RAAS) by angiotensin converting enzyme
inhibitors (ACEI) and angiotensin receptor blockers (ARBs) is considered the first-choice of
drugs for treatment of hypertension, heart failure and chronic kidney disease However, the
interplay between RAAS blockers and ACE2 hasn't been fully elucidated SARS-CoV-2 is thought
to infect host cells through ACE2 to cause coronavirus disease 2019 (COVID-19). Recent
studies revealed that the spikes of COVID-19 could bind to the surface receptors of sensitive
cells after contacting the airway surface, which may mediate virus entry into target cells
and viral replication, and ACE2 might be a mediator of infection (South, Brady et al. 2020).
Therefore, the imbalance in the RAAS, with a shift towards ACE/Ang II and suppression of
ACE2/Ang-(1-7), may be an important mediator of COVID-19. To date, conflicting evidences were
reported linking the use of RAAS blockers and the susceptibility to the virus. However,
others showed that treatment with an RAAS blockers may downregulate the expression of ACE2
but have no significant effect on its activity This research importantly aimed to solve this
important issue by determining the exact association between ARBs and ACE inhibitor and ACE2
activity and levels on clinical and experimental prospects.
Description:
Blockage of renin-angiotensin-aldosterone system (RAAS) by angiotensin converting enzyme
inhibitors (ACEI) and angiotensin receptor blockers (ARBs) is considered the first-choice of
drugs for treatment of hypertension, heart failure and chronic kidney disease . The classic
RAAS primarily involves 2 enzymes: renin, which cleaves angiotensinogen to the inactive
decapeptide angiotensin (Ang) I; and ACE that hydrolyzes Ang I to the octapeptide Ang II, the
well-known vasopressor agent . In fact, the enzymatic cascade of the RAS encompasses an ACE
homolog known as ACE2. Whereas, the ACE2-dependent pathways directly yield Ang (1-9) from Ang
I and degrade Ang II to Ang (1-7), which is vasodilator and acts as a feedback mechanism to
antagonize the vasopressor effect of Ang II. Indeed, ACE inhibitors effectively attenuate Ang
II formation and augment the levels of the heptapeptide Ang (1-7) . However, the interplay
between RAAS blockers and ACE2 hasn't been fully elucidated.
SARS-CoV-2 is thought to infect host cells through ACE2 to cause coronavirus disease 2019
(COVID-19). Recent studies revealed that the spikes of COVID-19 could bind to the surface
receptors of sensitive cells after contacting the airway surface, which may mediate virus
entry into target cells and viral replication, and ACE2 might be a mediator of infection
Therefore, the imbalance in the RAAS, with a shift towards ACE/Ang II and suppression of
ACE2/Ang-(1-7), may be an important mediator of COVID-19. To date, conflicting evidences were
reported linking the use of RAAS blockers and the susceptibility to the virus. However,
others showed that treatment with an RAAS blockers may downregulate the expression of ACE2
but have no significant effect on its activity .
Furthermore, SARS-CoV-2 infection has largely been influenced by multiorgan involvement
inducing multiple comorbidities due to the wide distribution of ACE2 thought out the whole
body. In addition, hypertension, cardiovascular disease, and chronic kidney disease are
supposed to be potential but unconfirmed risk factors for COVID-19 in adults and children .
However, the expression of ACE2 may be lower in patients with hypertension than in people
with normal blood pressure . Concluding more conflicting evidences for the association of
COVID-19 with RAAS inhibitors.
Given the RAAS importance to cardiovascular and kidney physiology, and the association
between chronic diseases and COVID-19, could shed light on potential relationships between
ACE inhibitor and ARB use and COVID-19.
Accordingly, evidences are required to solve the question of whether ARBs and ACE inhibitor
have either favorable or harmful effects on the susceptibility to SARS-CoV-2 in addition to
the severity and outcomes of COVID-19 infection. This research importantly aimed to solve
this important issue by determining the exact association between ARBs and ACE inhibitor and
ACE2 activity and levels on clinical and experimental prospects.
