Angiotensin Metabolite Profile After Subarachnoid Hemorrhage

Subarachnoid Hemorrhage, Aneurysmal Clinical Trial

Official title:

Angiotensin Metabolite Profile After Subarachnoid Hemorrhage

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05222542
• Other study ID #: EK Nr: 1681/2021
• Status: Recruiting
• Start date: March 1, 2022
• Est. completion date: February 2025

Study information

• Verified date: March 2022
• Source: Medical University of Vienna
• Contact: Katharina Krenn, MD, PhD
• Phone: +43140400
• Email: katharina.krenn[@]meduniwien.ac.at
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

The outcome of subarchnoid hemorrhage depends on the severity of the bleeding and the development of secondary neurologic deficits caused by cerebral vasospasm. The primary endpoint is a comparison of renin angiotensin system (RAS) parameters (plasma concentrations of Angiotensin [Ang] I, Ang II, Ang 1-7, and Ang 1-5, angiotensin metabolite based markers of RAS enzyme activities as well as active ACE and ACE2 concentrations in plasma and CSF) between patients with and without vasospasm, mechanical ventilation, antihypertensive therapy with a RAS modifying drug and low versus high Hunt and Hess grade of subarachnoid hemorrhage.

Description:

Wider research context. The clinical course and neurological outcome of patients with subarachnoid hemorrhage following rupture of an intracranial aneurysm depend on surgical repair of the ruptured aneurysm to avoid rebleeding and the development of cerebral vasospasm that may cause delayed ischemic deficits. Up to 65% of patients require mechanical ventilation mostly due to neurologic deficits or hypoxia. The renin angiotensin system (RAS) is acutely activated after subarachnoid hemorrhage with increased renin and angiotensin (Ang) II plasma levels, but effects of the vasoconstrictor Ang II on development of vasospasm have not been investigated in patients. The RAS may also be activated by mechanical ventilation, but it is unknown if this has an impact on occurrence of vasospasm. Arterial hypertension is an important risk factor for subarachnoid hemorrhage and vasospasm, and around 50% of patients have a history of high blood pressure. During weaning from mechanical ventilation arterial hypertension is a wide spread clinical problem, but how RAS modifying drugs act on the angiotensin metabolite profile that may already be dysregulated after subarachnoid hemorrhage remains unclear.

Objectives. To investigate associations between angiotensin metabolite profile (Ang I, Ang II, Ang 1-7 and Ang 1-5 concentrations) and angiotensin converting enzyme (ACE) and ACE2 activities in plasma as well as ACE and ACE2 activities in cerebrospinal fluid (CSF) and development of cerebral vasospasm in patients with and without mechanical ventilation following subarachnoid hemorrhage, and to find out how the angiotensin metabolite profile is changed by antihypertensive therapy with a RAS modifying drug in these patients.

Methods. Ang I, Ang II, Ang 1-7 and Ang 1-5 equilibrium concentrations will be measured by liquid chromatography tandem mass spectrometry in 60 patients after subarachnoid hemorrhage in plasma. Active ACE and ACE2 concentrations will be measured in plasma and in CSF in patients with CSF drainages. Samples will be taken within 72 hours of subarachnoid hemorrhage and 7, 14 and 21 days following initial bleeding. Another plasma sample will be obtained if an antihypertensive therapy with a RAS modifying drug has been started. Angiotensin metabolite based markers of RAS enzyme activities will be calculated for renin and ACE activities and alternative RAS activation.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 60
• Est. completion date: February 2025
• Est. primary completion date: February 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 85 Years

Eligibility

Inclusion Criteria:

• Patients with a diagnosis of subarachnoid hemorrhage because of aneurysmal rupture admitted to the ICU

• Invasive monitoring of arterial blood pressure

Exclusion Criteria:

• Patients who decline study participation

• Brain stem death

• Chronic renal impairment with creatinine > 2mg/dL or hemodialysis

• Chronic liver failure of Child Pugh class C or higher

• Chronic heart failure

• Hormone producing neuroendocrine tumor

• Sarcoidosis

• Pregnancy

• Planned transfer to another hospital shortly after aneurysm repair

Related Conditions & MeSH terms

• Hemorrhage
• Subarachnoid Hemorrhage
• Subarachnoid Hemorrhage, Aneurysmal

Intervention

Other:
• Sampling of plasma and cerebrospinal fluid at specified time points
Samples (plasma, and in patients with in-dwelling cerebrospinal fluid drainages also cerebrospinal fluid) will be taken within 72 hours of subarachnoid hemorrhage and 7, 14 and 21 days following initial bleeding. Another plasma sample will be obtained if an antihypertensive therapy with a RAS modifying drug has been started.

Locations

Country	Name	City	State
Austria	Medical University of Vienna	Vienna

Sponsors (2)

Lead Sponsor	Collaborator
Dr. Roman Ullrich	Austrian Science Fund (FWF)

Country where clinical trial is conducted

Austria, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Angiotensin metabolite concentrations within 72 hours	Ang I, Ang II, Ang 1-7 and Ang 1-5 equilibrium concentrations in plasma (in pmol/L), comparison between patients with and without vasospasm, with and without mechanical ventilation and low versus high Hunt and Hess grade	within 72 hours of subarachnoid hemorrhage
Primary	Angiotensin metabolite concentrations after 7 days	Ang I, Ang II, Ang 1-7 and Ang 1-5 equilibrium concentrations in plasma (in pmol/L), comparison between patients with and without vasospasm, with and without mechanical ventilation and low versus high Hunt and Hess grade	7 days after subarchnoid hemorrhage
Primary	Angiotensin metabolite concentrations after 14 days	Ang I, Ang II, Ang 1-7 and Ang 1-5 equilibrium concentrations in plasma (in pmol/L), comparison between patients with and without vasospasm, with and without mechanical ventilation and low versus high Hunt and Hess grade	14 days after subarchnoid hemorrhage
Primary	Angiotensin metabolite concentrations after 21 days	Ang I, Ang II, Ang 1-7 and Ang 1-5 equilibrium concentrations in plasma (in pmol/L), comparison between patients with and without vasospasm, with and without mechanical ventilation and low versus high Hunt and Hess grade	21 days after subarchnoid hemorrhage
Primary	ACE concentrations within 72 hours	active ACE concentrations in plasma and cerebrospinal fluid (in µg/mL), comparison between patients with and without vasospasm, with and without mechanical ventilation and low versus high Hunt and Hess grade	within 72 hours of subarachnoid hemorrhage
Primary	ACE concentrations after 7 days	active ACE concentrations in plasma and cerebrospinal fluid (in µg/mL), comparison between patients with and without vasospasm, with and without mechanical ventilation and low versus high Hunt and Hess grade	7 days after subarachnoid hemorrhage
Primary	ACE concentrations after 14 days	active ACE concentrations in plasma and cerebrospinal fluid (in µg/mL), comparison between patients with and without vasospasm, with and without mechanical ventilation and low versus high Hunt and Hess grade	14 days after subarachnoid hemorrhage
Primary	ACE concentrations after 21 days	active ACE concentrations in plasma and cerebrospinal fluid (in µg/mL), comparison between patients with and without vasospasm, with and without mechanical ventilation and low versus high Hunt and Hess grade	21 days after subarachnoid hemorrhage
Primary	ACE2 concentrations within 72 hours	active ACE2 concentrations in plasma and cerebrospinal fluid (in ng/mL), comparison between patients with and without vasospasm, with and without mechanical ventilation and low versus high Hunt and Hess grade	within 72 hours of subarachnoid hemorrhage
Primary	ACE2 concentrations after 7 days	active ACE2 concentrations in plasma and cerebrospinal fluid (in ng/mL), comparison between patients with and without vasospasm, with and without mechanical ventilation and low versus high Hunt and Hess grade	7 days after subarachnoid hemorrhage
Primary	ACE2 concentrations after 14 days	active ACE2 concentrations in plasma and cerebrospinal fluid (in ng/mL), comparison between patients with and without vasospasm,with and without mechanical ventilation and low versus high Hunt and Hess grade	14 days after subarachnoid hemorrhage
Primary	ACE2 concentrations after 21 days	active ACE2 concentrations in plasma and cerebrospinal fluid (in ng/mL), comparison between patients with and without vasospasm, with and without mechanical ventilation and low versus high Hunt and Hess grade	21 days after subarachnoid hemorrhage
Primary	Impact of RAS modifying drugs after subarachnoid hemorrhage	Ang I, Ang II, Ang 1-7 and Ang 1-5 equilibrium concentrations in plasma (in pmol/L), comparison between sample taken after start of a RAS modifying drug and the previous sample in the study schedule	after start of a RAS modifying drug therapy for arterial hypertension in the intensive care unit
Secondary	Correlation of RAS analyses with clinical parameters	Correlations of RAS parameters (Ang I, Ang II, Ang 1-7 and Ang 1-5 equilibrium concentrations and active ACE and ACE2 concentrations) and aldosterone plasma concentrations with blood pressure, blood pressure target, routine laboratory parameters and ventilator settings, and comparison of RAS parameters and aldosterone plasma concentrations between men and women	Within 72 hours, 7, 14 and 21 days following subarachnoid hemorrhage and after start of a RAS modifying drug therapy for arterial hypertension in the intensive care unit