Angiotensin Metabolite Profile After Subarachnoid Hemorrhage

NCT05222542 | Unknown

• 1 other identifier: EK Nr: 1681/2021
• Study Type: observational
• Target: 60
• Locations: 1 country
• Sites: 1

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.

Conditions

Subarachnoid Hemorrhage, Aneurysmal

Keywords

Cerebral vasospasm; Renin angiotensin system

Outcome Measures

Primary Outcomes (13)

• 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

• 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

• 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

• 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

• 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

• 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

• 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

• 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

• 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

• 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

• 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

• 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

• 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 Outcomes (1)

• Correlation of RAS analyses with clinical parameters

  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

Study Arms (1)

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.

Other: Sampling of plasma and cerebrospinal fluid at specified time points

Interventions

Sampling of plasma and cerebrospinal fluid at specified time points 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.

Patients after aneurysmal subarachnoid hemorrhage

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

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

You may qualify if:

• Patients with a diagnosis of subarachnoid hemorrhage because of aneurysmal rupture admitted to the ICU
• Invasive monitoring of arterial blood pressure

You may not qualify if:

• 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

Sponsors & Collaborators

• Dr. Roman Ullrich: lead
• Austrian Science Fund (FWF): collaborator

Study Sites (1)

Medical University of Vienna

Vienna, A-1090, Austria

RECRUITING

Biospecimen

Retention: SAMPLES WITH DNA

Plasma (without DNA) and cerebrospinal fluid (potentially containing cellular residues with DNA)

MeSH Terms

Conditions

Subarachnoid Hemorrhage; Vasospasm, Intracranial

Condition Hierarchy (Ancestors)

Intracranial Hemorrhages; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Hemorrhage; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Katharina Krenn, MD, PhD

  Medical University of Vienna

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Katharina Krenn, MD, PhD

CONTACT

+43140400; katharina.krenn@meduniwien.ac.at

Roman Ullrich, MD

CONTACT

roman.ullrich@meduniwien.ac.at

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Prof., sub-investigator

Study Record Dates

• First Submitted: January 11, 2022
• First Posted: February 3, 2022
• Study Start: March 1, 2022
• Primary Completion: February 1, 2025
• Study Completion: February 1, 2025
• Last Updated: March 2, 2022

Record last verified: 2022-03

Data Sharing

• IPD Sharing: Will not share

Locations

AU (1)