The study will investigate infections with the new SARS-CoV2 virus. Current studies show that the SARS-CoV2 virus penetrates human cells via the angiotensin converting enzyme II (ACE2) receptor 2. Experimental studies show that ACE inhibitors (ACEI) and angiotensin receptor blockers (ARB) can increase the expression of ACE2 and thus could facilitate virus uptake. This study will investigate the effect of stopping chronic ACEI or ARB therapy in patients with proven SARS-CoV2 infection.
Conditions
Sponsors
Medizinische Universität Innsbruck
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Written, signed and dated informed consent form to participate in the clinical trial after prior written and oral information 2. Male and female patients = 18 years capable of making decisions 3. Confirmed symptomatic SARS-CoV2 infection (throat swab) = 5 days 4. Chronic (=1 month) pretreatment with medicinal products from the ATC groups C09A, C09B, C09C, C09D due to arterial hypertension, diabetes mellitus, heart failure or coronary heart disease. 5. Stable circulatory conditions with not more than four antihypertensive drugs, which allow discontinuation of the therapy with a medicinal product from the ATC groups C09A, C09B, C09C, C09D (systolic arterial blood pressure =180mmHg). Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 160 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 638
Exclusion criteria
Exclusion criteria: 1. Women of childbearing potential including pregnant women and breastfeeding mothers 2. Participation in another interventional study 3. At the time of study inclusion oral medication is not possible 4. Acute coronary syndrome =3 months 5. Heart failure in stages NYHA III and IV 6. Restriction of left ventricular ejection fraction 4 antihypertensive drugs) 10. Therapy-refractory arterial hypertension (systolic arterial blood pressure >180mmHg despite multiple therapy) 11. Patients who cannot be switched to alternative therapy. 12. Patients who cannot perform a blood pressure self-measurement under ambulant conditions
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Patients with coronary artery disease, arterial hypertension or diabetes are often treated with angiotensin converting enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARB). Treatment with ACEI and ARB may be of great relevance for the course of COVID-19: Similar to SARS-CoV (epidemic 2002-2003), the novel SARS-CoV2 is also absorbed into human cells via angiotensin converting enzyme 2 (ACE2). Treatment with ACEI and ARB leads to a significant upregulation of the SARS-CoV2 receptor ACE2. An increased expression of ACE2 in turn correlates with a higher intake of SARS-CoV2 and possibly promotes a faster spread of the virus in the organism of infected patients. The primary aim of the study is to test whether discontinuing chronic ACEI or ARB therapy in patients with proven SARS-CoV2 infection leads to a more favorable course of the disease of COVID-19 than the continuation of the ACEI or ARB therapy.;Secondary Objective: Secondarily, the effect of discontinuation on clinical and laboratory parameters of SARS-CoV2 therapy is examined.;Primary end point(s): Two primary endpoints are tested hierarchically: Primary endpoint 1 is the combination of the maximum SOFA scores measured during the course of the disease (=30 days) and death. The minimum SOFA score is 0 and the maximum is 24. In the event of death, the patient receives the maximum value of 24 points. Patients in the ambulant setting receive a value of 0. Patients in the stationaire setting who are not ventilated receive 0 points for the parameter "Respiration" (variable PaO2 / FiO2). Clinical trials have demonstrated that the maximum SOFA score correlates with mortality. Primary endpoint 2 is the combination of a combination of intensive care admission, intubation and death.;Timepoint(s) of evaluation of this end point: During the course of the disease (=30 days ±2 days) | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Maximum and medium SOFA score 2. Area under the SOFA curve (AUC) 3. Death 4. Hospitalization 5. Intensive care admission 6. Intubation 7. Combination of intensive care admission, intubation and death 8. Non-invasive ventilation (CPAP, high-flow etc.) 9. ECMO treatment 10. Renal replacement therapy 11. Quality of Life (EQ-5D-3L) 12. Change in viral load (only if clinically determined) 13. C-reactive protein (CRP), D-dimer, IL-6, highly sensitive troponin (hsTN), NT-pro-BNP, lymphocytes, eosinophil and platelet count, ferritin, transferrin, LDH, procalcitonin, neopterin 14. Identification of biomarkers (cellular immune status, soluble biomarkers, CHIP, transcription patterns at single cell level) 15. Seroconversion;Timepoint(s) of evaluation of this end point: After the last visit at day 30 (±2 days) | — |
Countries
Austria, Germany
Contacts
Public ContactUniv.-Prof. Dr. Axel Bauer
Medizinische Universität Innsbruck, Univ.-Klinik für Innere Medizin III
Outcome results
None listed