Prognosis of Coronavirus Disease 2019 (COVID-19) Patients Receiving Receiving Antihypertensives

COVID-19 Clinical Trial

Official title:

Prognosis of SARS-Cov 2 Positive Patients Receiving Angiotensin Converting Enzyme Inhibitors (ACE-I) and Angiotensin II Receptor Antagonists (ARBs)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04357535
• Other study ID #: 2210061
• Status: Completed
• Start date: May 10, 2020
• Est. completion date: August 1, 2020

Study information

• Verified date: July 2020
• Source: King Faisal Specialist Hospital & Research Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Coronavirus disease 2019 (COVID-19) ,caused by the newly identified Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) virus, has shown substantial global spread affecting over 2 million people and claiming over 120,000 lives to date. In March 2020, the World Health Organization (WHO) declared COVID-19 a global pandemic. The spectrum of manifestations of COVID19 infection ranges from mild flu-like symptoms to severe acute respiratory distress syndrome (ARDS), with an associated fatality rate of 1.4%. The suggested mode of entry of the SARS-CoV-2 into the human respiratory epithelium is through the angiotensin-converting enzyme 2 (ACE2) protein expressed on alveolar cell surfaces. This entry mechanism has sparked the interest of the scientific community. Preliminary epidemiological reports showed an increased risk of ARDS in hypertensive COVID-19 patients. This leads to the hypothesis that hypertensives treated with angiotensin-converting enzyme inhibitor (ACE-I) are at an increased risk of developing complicated COVID-19 infections . Other studies have refuted these claims as unsupported. Studies revealing the up regulation of ACE2 in cells of patients treated with ACE-I or ARBs were the underlying foundation for these claims. This study aims to assess the impact of ACE-I and/or ARBs on the prognosis of patients with COVID19.

Description:

Design and Patients: this is a prospective, observational multi-center study, to be conducted at King Faisal Specialist Hospital and Research Centre (KFSH & RC), Riyadh, Saudi Arabia as a primary center. Collaborating centers are Buraidah Central hospital,King Khalid University Hospital and King Abdullah bin Abdulaziz University Hospital (affiliate of Princess Nourah Bint Abdulrahman University)

Sample size: 226 subjects.

Protocol: Patients diagnosed with COVID19 infection via positive polymerase chain reaction (PCR) test will be screened for one of the following five comorbidity (hypertension, diabetes mellitus, cerebrovascular disease, coronary artery disease, and heart failure) will be identied on admission to hospital. The use of ACE-I and ARBs or other antihypertensive medications will be recorded. Additional information to be gathered will include the following: patient demographics (age, sex, weight, and height), indication for ACE-I or ARB therapy, duration therapy and doses; plasma or serum levels of the following laboratories will be obtained on admission: creatinine levels, lactate dehydrogenase, creatinine kinase, ferritin, D-Dimer, and c-reactive protein. The date of positive COVID19 PCR; admission to the intensive care unit (ICU) with calculating the Sequential Organ Failure Assessment (SOFA) score. The requirement of mechanical ventilation and vasopressors will be recorded with a length of ICU stay. Patients fulfilling the criteria of acute respiratory distress (ARDS) will be recorded, and the PF ratio will be assessed for all subjects admitted to the ICU. Patient who die in ICU or during hospitalization will be recorded. The entirety of the hospitalization period will be determined and recorded.

Outcome Assessment: The primary endpoint will be the severity of COVID-19 infection, described as the composite of admission to the intensive care unit, requirement for invasive mechanical ventilation or death. The use of ACE-I and ARBs will be assessed independently for associations with severity of respiratory disease.

The rate of patients using ACE-I or ARBs will be reported with the indications for their use. The association of ACE-I or ARBs with prognosis of patients with COVID19 will be reported.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 314
• Est. completion date: August 1, 2020
• Est. primary completion date: July 1, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

Criteria Include patients infected with the COVID19 (via positive PCR) aged = 18 years with one of the following:

• Hypertension

• Coronary artery disease

• Heart failure

• Diabetes mellitus.

Exclusion Criteria:

• Pregnancy

Related Conditions & MeSH terms

• COVID-19

Intervention

Drug:
• Angiotensin-Converting Enzyme Inhibitors (ACE-I) and Angiotensin II Receptor Blockers (ARB)
ACE-I and ARB are a class of blood pressure lowering medications used to manage hypertension.

Locations

Country	Name	City	State
Saudi Arabia	King Faisal Specialist Hospital & Research Centre	Riyadh

Sponsors (4)

Lead Sponsor	Collaborator
Hakeam Abdulaziz Hakeam	Buraidah Central Hospital, King Khalid University Hospital, Princess Nourah Bint Abdulrahman University

Country where clinical trial is conducted

Saudi Arabia, 

References & Publications (5)

Esler M, Esler D. Can angiotensin receptor-blocking drugs perhaps be harmful in the COVID-19 pandemic? J Hypertens. 2020 May;38(5):781-782. doi: 10.1097/HJH.0000000000002450. — View Citation

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. — View Citation

Patel AB, Verma A. COVID-19 and Angiotensin-Converting Enzyme Inhibitors and Angiotensin Receptor Blockers: What Is the Evidence? JAMA. 2020 Mar 24. doi: 10.1001/jama.2020.4812. [Epub ahead of print] — View Citation

Wu C, Chen X, Cai Y, Xia J, Zhou X, Xu S, Huang H, Zhang L, Zhou X, Du C, Zhang Y, Song J, Wang S, Chao Y, Yang Z, Xu J, Zhou X, Chen D, Xiong W, Xu L, Zhou F, Jiang J, Bai C, Zheng J, Song Y. Risk Factors Associated With Acute Respiratory Distress Syndrome and Death in Patients With Coronavirus Disease 2019 Pneumonia in Wuhan, China. JAMA Intern Med. 2020 Mar 13. doi: 10.1001/jamainternmed.2020.0994. [Epub ahead of print] — View Citation

Zhou P, Yang XL, Wang XG, Hu B, Zhang L, Zhang W, Si HR, Zhu Y, Li B, Huang CL, Chen HD, Chen J, Luo Y, Guo H, Jiang RD, Liu MQ, Chen Y, Shen XR, Wang X, Zheng XS, Zhao K, Chen QJ, Deng F, Liu LL, Yan B, Zhan FX, Wang YY, Xiao GF, Shi ZL. A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature. 2020 Mar;579(7798):270-273. doi: 10.1038/s41586-020-2012-7. Epub 2020 Feb 3. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Severity of COVID-19 Infection	Admission to intensive care unit, requirement for invasive ventilation or death	From date of study enrolment until discharge from hospital or death from any cause, whichever came first, assessed up to 4 weeks.
Secondary	Degree of severity of respiratory disease	PaO2/FiO2 ratio (PF) ratio	From date of study enrolment until discharge from hospital or death from any cause, whichever came first, assessed up to 4 weeks.
Secondary	Septic shock as defined by sepsis-3 criteria	Defined as sepsis with hypotension requiring vasopressors to maintain mean arterial pressure (MAP) 65 mm Hg and having a serum lactate level >2 mmol/L (18 mg/dL) despite adequate volume resuscitation.	From date of study enrolment until discharge from hospital or death from any cause, whichever came first, assessed up to 4 weeks.

External Links

•   World Health Organization Data