Clinical trial NCT01799525: Hypercapnia to Prevent Secondary Ischemia in SAH
Official title: Therapeutical Hypercapnia to Prevent Secondary Ischemic Events in Aneurysmal Subarachnoid Hemorrhage (aSAH)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Aneurysmal Subarachnoid Hemorrhage
Keywords: Aneurysm
subarachnoid hemorrhage
vasospasm
cerebral ischemia
stroke
Lead sponsor: Wuerzburg University Hospital
Sponsor class: OTHER
First posted: 2013-02-26
Enrollment: 10
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Delayed cerebral vasospasm and secondary ischemic infarction are feared complications after aneurysmal subarachnoid hemorrhage (aSAH). To date, there is no effective therapy to prevent these ischemic complications. The arterial partial pressure of carbon dioxide (PaCO2) is one of the main determinants of cerebral blood flow (CBF) in healthy subjects. It is yet largely unknown, if and to what extent modulations of PaCO2 can influence CBF in patients after aSAH. The trial is a phase 1 study in which the feasibility of hypercapnia in SAH patients is tested. PaCO2 is gradually raised to 60 mmHg in 10 mechanically ventilated aSAH patients. Cerebral oxygen saturation measured by NIRS and CBF determined by an intracerebral thermodilution probe are the primary end points. If the feasibility is confirmed, this trial will be followed by a phase 2 dose finding study.

Detailed description: The course of aneurysmal subarachnoid hemorrhage (aSAH) is determined by the sequence of several ischemic episodes. Immediately after aSAH, an increase of ICP causes an increase of CBF. It is followed by an acute vasoconstriction over the next hours and days. Typically between day 4 and 10 after aSAH, delayed arterial narrowing and a decrease of CBF occurs in approximately 50 % of aSAH patients and may result in cerebral ischemia and infarction. After the failure of the CONSCIOUS-trial to improve outcome after aSAH, there is no specific treatment in sight to effectively prevent cerebral ischemic events after aSAH. Under physiological conditions, the arterial partial pressure of carbon dioxide (PaCO2) is one of the main determinants of cerebral blood flow (CBF). An elevation of PaCO2 may also be a useful treatment on aSAH patients. This trial is designed as a phase 1 study to test the feasibility of controlled hypercapnia in mechanically ventilated aSAH patients with poor-grade SAH. Monitoring is performed by an external ventricular drainage (ICP), near infrared spectroscopy (tissue oxygenation) and a thermodilution probe (CBF). The latter monitoring tools represent the primary end points of this study. In case of affirmed feasibility, a dose finding study will be launched as a next step.

Eligibility criteria: Inclusion Criteria:

* aneurysmal SAH
* SAH Hunt/Hess Grade 3-5
* SAH Fisher Grade 2-4
* Mechanically ventilated
* external ventricular drainage/ICP measurement

Exclusion Criteria:

* Age under 18
* ICP \> 25 mmHg for \> 2 minutes
* pH \< 7.250

Primary outcomes:
measure: Cerebral Blood Flow
timeFrame: For an average of two weeks after aSAH
Secondary outcomes:
measure: Cerebral oxygen saturation
timeFrame: For an average of two weeks after aSAH
measure: intracranial pressure (ICP)
timeFrame: For an average of two weeks
Other outcomes:
Locations:
city: Wuerzburg
country: Germany
facility: Department of Neurosurgery, University of Wuerzburg
state: Bavaria
Study officials:
affiliation: Department of Neurosurgery, University of Wuerzburg, Germany
name: Thomas Westermaier, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Department of Neurosurgery, University of Wuerzburg
name: Ekkehard Kunze, MD
role: STUDY_DIRECTOR
References:
citation: Stetter C, Weidner F, Lilla N, Weiland J, Kunze E, Ernestus RI, Muellenbach RM, Westermaier T. Therapeutic hypercapnia for prevention of secondary ischemia after severe subarachnoid hemorrhage: physiological responses to continuous hypercapnia. Sci Rep. 2021 Jun 3;11(1):11715. doi: 10.1038/s41598-021-91007-7.
citation: Westermaier T, Stetter C, Kunze E, Willner N, Holzmeier J, Kilgenstein C, Lee JY, Ernestus RI, Roewer N, Muellenbach RM. Controlled transient hypercapnia: a novel approach for the treatment of delayed cerebral ischemia after subarachnoid hemorrhage? J Neurosurg. 2014 Nov;121(5):1056-62. doi: 10.3171/2014.7.JNS132611. Epub 2014 Aug 22.