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ACE Inhibitors, Angiotensin II Type-I Receptor Blockers and Severity of COVID-19 (CODIV-ACE)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04318418
Recruitment Status : Completed
First Posted : March 24, 2020
Last Update Posted : September 16, 2020
Sponsor:
Information provided by (Responsible Party):
Augusto Di Castelnuovo, Neuromed IRCCS

Brief Summary:

Hypothesis Very recent evidences supports the hypothesis that the novel coronavirus 2019 (2019-nCoV) uses the SARS-1 (severe acute respiratory syndrome

) coronavirus receptor angiotensin converting enzyme 2 (ACE2) for entry into target cells. The epidemiological association between Angiotensin receptor-blocker (ARB) or ACE inhibitors (ACE-I) use and severe sequelae of 2109-nCoV infection disease COVID-19 has not been yet conclusively demonstrated, but may have important consequences for population health.

Aim To retrospectively test whether 2019-nCoV patients treated with ACE-I or ARB, in comparison with patients who not, are at higher risk of having severe COVID-19 (including death).

Population Hospitalized patients with confirmed COVID-19 infection (any type).

Study design Patients will be divided in two groups, a) controls: individuals who did not develop severe COVID-19 respiratory disease (including individuals who recovered from the infection) and b) cases: individuals who developed severe COVID-19 disease (including fatal events). Treatment with ACE-I or ARB, together with possible confounding will be assessed retrospectively.

Exposure Treatment for ACE-I or ARB.


Condition or disease
COVID-19

Detailed Description:

Background Very recent evidences support the hypothesis that the novel coronavirus 2019 (2019-nCoV) uses the SARS-1 coronavirus receptor ACE2 for gains entry into target cells. Angiotensin receptor-blocker (ARB) drugs, one of the most commonly used antihypertensive drug, typically increase ACE2 expression, often very markedly. With SARS-CoV-2 infection increased ACE2 expression very definitely would not be beneficial, and could be adverse. However, augmented ACE2 expression with ARB has been demonstrated in the kidneys and heart but has not been tested in the lungs. So, the hypothesis that using of ARB or ACE inhibitors (ACE-I) drugs during the COVID-19 may possibly be harmful is urgently to be verified in epidemiological studies.

Aim To retrospectively test whether 2019-nCoV patients treated with ARB or ACE-I, in comparison with patients who not, are at higher risk of having severe COVID-19 (coronavirus infection disease 2019), including death.

Population Hospitalized patients with confirmed COVID-19 infection (any type).

Outcome The project will retrospectively collect data on the most severe manifestation of COVID-19 occurred in 2019-nCoV infected patients during hospitalization. Severity will be classified as: hospital discharge with healing, asymptomatic, mild complications but not pneumonia, not severe pneumonia, severe pneumonia, acute respiratory distress syndrome (ARDS) and death. Classification of pneumonia will follow WHO (World Health Organization) criteria. Data on severity will be obtained from medical record at one-point time (at the moment of inclusion in the study).

Exposure Treatment for ARB or ACE-I. When available, type of drugs will be recorded.

Study design Patients will be divided in two groups, a) controls: individuals who did not develop severe COVID-19 respiratory disease (including individuals who recovered from the infection) and b) cases: individuals who developed severe COVID-19 disease (including fatal events). Association between use of ACE-I or ARB and severity of COVID-19 will be assessed by using of multivariable logistic regression analysis. Data on potential confounders will be obtained by medical records: age, sex, time intervals from hospital admission to worse manifestation of COVID-19 and to eventual death or recovering, smoking, body mass index, history of myocardial infarction, diabetes, hypertension, cancer, respiratory disease, other morbidities, creatinine, insulin, glomerular filtration rate together with use of Tocilizumab, anti-aldosterone agents, diuretics, Kaletra, cortisone, Remdesivir, Hydroxychloroquine, Sacubitril or Valsartan.

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Study Type : Observational
Actual Enrollment : 3400 participants
Observational Model: Cohort
Time Perspective: Retrospective
Official Title: ACE Inhibitors, Angiotensin II Type-I Receptor Blockers and Severity of COVID-19
Actual Study Start Date : March 23, 2020
Actual Primary Completion Date : May 10, 2020
Actual Study Completion Date : June 30, 2020

Resource links provided by the National Library of Medicine


Group/Cohort
Cases
Patients who developed severe COVID-19 disease (including fatal events)
Controls
Infected patients who did not develop severe COVID-19 respiratory disease (including individuals who recovered from the infection)



Primary Outcome Measures :
  1. Severe COVID-19 [ Time Frame: 1 month ]
    Severity pneumonia or acute respiratory distress syndrome by COVID-19


Secondary Outcome Measures :
  1. Death [ Time Frame: 1 month ]
    Death by COVID-19



Information from the National Library of Medicine

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Ages Eligible for Study:   Child, Adult, Older Adult
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
Hospitalized patients with confirmed COVID-19 infection (any type), recruited in Italian hospital
Criteria

Inclusion Criteria:

Patients hospitalized for COVID-19

Exclusion Criteria:

none


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04318418


Locations
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Italy
IRCCS Neuromed, Department of Epidemiology and Prevention
Pozzilli, Italy, 86077
Sponsors and Collaborators
Neuromed IRCCS
Investigators
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Principal Investigator: Augusto Di Castelnuovo, MSc, PhD IRCCS Neuromed
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Di Castelnuovo A, Costanzo S, Antinori A, Berselli N, Blandi L, Bonaccio M, Cauda R, Gialluisi A, Guaraldi G, Menicanti L, Mennuni M, Mussinelli R, My I, Parruti G, Patti G, Perlini S, Santilli F, Signorelli C, Stefanini GG, Vergori A, Abete P, Ageno W, Agostoni P, Aiello L, Al Moghazi S, Arboretti R, Aucella F, Barbieri G, Barchitta M, Bartoloni A, Bonfanti P, Cacciatore F, Caiano L, Carrozzi L, Cascio A, Castiglione G, Cianfrone S, Ciccullo A, Cingolani A, Cipollone F, Colomba C, Colombo C, Cozzi O, Crisetti A, Crosta F, Danzi GB, D'Ardes D, de Gaetano Donati K, Di Gennaro F, Di Tano G, D'Offizi G, Fusco FM, Gentile I, Graziani E, Guarnieri G, Larizza G, Leone A, Lio V, Lucia MB, Maccagni G, Madaro F, Maitan S, Mancarella S, Manuele R, Mapelli M, Maragna R, Marcucci R, Maresca G, Marongiu S, Marotta C, Marra L, Mastroianni F, Mazzitelli M, Mengozzi A, Menichetti F, Meschiari M, Milic J, Minutolo F, Molena B, Mussini C, Musso M, Odone A, Olivieri M, Palimodde A, Pasi E, Pesavento R, Petri F, Pinchera B, Pivato CA, Poletti V, Ravaglia C, Rossato M, Rossi M, Sabena A, Salinaro F, Sangiovanni V, Sanrocco C, Scoppettuolo G, Scorzolini L, Sgariglia R, Simeone PG, Trecarichi EM, Vettor R, Vianello A, Vinceti M, Virano A, Vocciante L, Iacoviello L, Caterina. RAAS inhibitors are not associated with mortality in COVID-19 patients: findings from an observational multicenter study in Italy and a meta-analysis of 19 studies. Vascul Pharmacol. 2020 Sep 26:106805. doi: 10.1016/j.vph.2020.106805. [Epub ahead of print]

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Responsible Party: Augusto Di Castelnuovo, MSc, PhD, Neuromed IRCCS
ClinicalTrials.gov Identifier: NCT04318418    
Other Study ID Numbers: DEP_012020
First Posted: March 24, 2020    Key Record Dates
Last Update Posted: September 16, 2020
Last Verified: September 2020

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Augusto Di Castelnuovo, Neuromed IRCCS:
Angiotensin receptor-blocker and ACE inhibitors drugs