Angiotensin Metabolite Profile After Subarachnoid Hemorrhage

NCT ID: NCT05222542

Last Updated: 2022-03-02

Basic Information

• Recruitment Status: UNKNOWN
• Total Enrollment: 60 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2022-03-01
• Study Completion Date: 2025-02-28

Brief 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.

Detailed 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.

Conditions

Subarachnoid Hemorrhage, Aneurysmal

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

Patients after aneurysmal subarachnoid hemorrhage

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.

Sampling of plasma and cerebrospinal fluid at specified time points

Intervention Type: OTHER

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.

Interventions

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.

Intervention Type: OTHER

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 85 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Austrian Science Fund (FWF)

OTHER

Sponsor Role: collaborator

Dr. Roman Ullrich

OTHER

Sponsor Role: lead

Responsible Party

Dr. Roman Ullrich

Prof., sub-investigator

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Katharina Krenn, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Medical University of Vienna

Locations

Medical University of Vienna

Vienna, , Austria

Site Status: RECRUITING

Countries

Austria

Central Contacts

Katharina Krenn, MD, PhD

Role: CONTACT

katharina.krenn@meduniwien.ac.at

+43140400 ext. 41020

Roman Ullrich, MD

Role: CONTACT

roman.ullrich@meduniwien.ac.at

Facility Contacts

Katharina Krenn, MD, PhD

Role: primary

katharina.krenn@meduniwien.ac.at

+43140400 ext. 41020

Head of Department (Anesthesia and General Intensive Care)

Role: backup

klaus.markstaller@meduniwien.ac.at

Other Identifiers

EK Nr: 1681/2021

Identifier Type: -

Identifier Source: org_study_id