Clinical trial NCT05222542: Angiotensin Metabolite Profile After Subarachnoid Hemorrhage
Official title: Angiotensin Metabolite Profile After Subarachnoid Hemorrhage
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Subarachnoid Hemorrhage, Aneurysmal
Keywords: Cerebral vasospasm
Renin angiotensin system
Lead sponsor: Medical University of Vienna
Sponsor class: OTHER
Collaborators: name: Austrian Science Fund (FWF)
First posted: 2022-02-03
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Patients with a diagnosis of subarachnoid hemorrhage because of aneurysmal rupture admitted to the ICU

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.

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

Primary outcomes:
measure: Angiotensin metabolite concentrations within 72 hours
timeFrame: within 72 hours of subarachnoid hemorrhage
measure: Angiotensin metabolite concentrations after 7 days
timeFrame: 7 days after subarchnoid hemorrhage
measure: Angiotensin metabolite concentrations after 14 days
timeFrame: 14 days after subarchnoid hemorrhage
measure: Angiotensin metabolite concentrations after 21 days
timeFrame: 21 days after subarchnoid hemorrhage
measure: ACE concentrations within 72 hours
timeFrame: within 72 hours of subarachnoid hemorrhage
measure: ACE concentrations after 7 days
timeFrame: 7 days after subarachnoid hemorrhage
measure: ACE concentrations after 14 days
timeFrame: 14 days after subarachnoid hemorrhage
measure: ACE concentrations after 21 days
timeFrame: 21 days after subarachnoid hemorrhage
measure: ACE2 concentrations within 72 hours
timeFrame: within 72 hours of subarachnoid hemorrhage
measure: ACE2 concentrations after 7 days
timeFrame: 7 days after subarachnoid hemorrhage
measure: ACE2 concentrations after 14 days
timeFrame: 14 days after subarachnoid hemorrhage
measure: ACE2 concentrations after 21 days
timeFrame: 21 days after subarachnoid hemorrhage
measure: Impact of RAS modifying drugs after subarachnoid hemorrhage
timeFrame: after start of a RAS modifying drug therapy for arterial hypertension in the intensive care unit
Secondary outcomes:
measure: Correlation of RAS analyses with clinical parameters
timeFrame: 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
Other outcomes:
Locations:
city: Vienna
country: Austria
facility: Medical University of Vienna
Study officials:
affiliation: Medical University of Vienna
name: Katharina Krenn, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: