Hypercapnia to Prevent Secondary Ischemia in SAH (SAHCO2)
Primary Purpose
Aneurysmal Subarachnoid Hemorrhage
Status
Completed
Phase
Phase 1
Locations
Germany
Study Type
Interventional
Intervention
Hypercapnia by reduction of respiratory volume
Sponsored by
About this trial
This is an interventional treatment trial for Aneurysmal Subarachnoid Hemorrhage focused on measuring Aneurysm, subarachnoid hemorrhage, vasospasm, cerebral ischemia, stroke
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
Sites / Locations
- Department of Neurosurgery, University of Wuerzburg
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Hypercapnia
Arm Description
Intervention: SAH patients are subjected to gradual hypercapnia by reduction of respiratory volume in one trial session every day. PaCO2 is raised from normocapnia to 50 mmHg for 10 - 15 minutes and 60 mmHg for 10 - 15 minutes.
Outcomes
Primary Outcome Measures
Cerebral Blood Flow
Between day 4 and 14, PaCO2 is gradually raised from normocapnic values (40 mmHg) to hypercapnic values (50 and 60 mmHg). CBF is continuously measured during this intervention. Patients are clinically and radiologically followed for 6 months.
Secondary Outcome Measures
Cerebral oxygen saturation
Oxygen saturation by NIRS is measured continuously for 2 weeks after aSAH.
intracranial pressure (ICP)
ICP is continuously measured by an external ventricular drainage throughout the intervention period.
Full Information
NCT ID
NCT01799525
First Posted
February 20, 2013
Last Updated
December 9, 2014
Sponsor
Wuerzburg University Hospital
1. Study Identification
Unique Protocol Identification Number
NCT01799525
Brief Title
Hypercapnia to Prevent Secondary Ischemia in SAH
Acronym
SAHCO2
Official Title
Therapeutical Hypercapnia to Prevent Secondary Ischemic Events in Aneurysmal Subarachnoid Hemorrhage (aSAH)
Study Type
Interventional
2. Study Status
Record Verification Date
December 2014
Overall Recruitment Status
Completed
Study Start Date
January 2013 (undefined)
Primary Completion Date
February 2014 (Actual)
Study Completion Date
August 2014 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Wuerzburg University Hospital
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Aneurysmal Subarachnoid Hemorrhage
Keywords
Aneurysm, subarachnoid hemorrhage, vasospasm, cerebral ischemia, stroke
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
Participant
Allocation
N/A
Enrollment
10 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Hypercapnia
Arm Type
Experimental
Arm Description
Intervention: SAH patients are subjected to gradual hypercapnia by reduction of respiratory volume in one trial session every day. PaCO2 is raised from normocapnia to 50 mmHg for 10 - 15 minutes and 60 mmHg for 10 - 15 minutes.
Intervention Type
Procedure
Intervention Name(s)
Hypercapnia by reduction of respiratory volume
Intervention Description
By reduction of the respiratory volume, PaCO2 is raised while paO2 is kept constant by modulation of the oxygen supply through the respirator,
Primary Outcome Measure Information:
Title
Cerebral Blood Flow
Description
Between day 4 and 14, PaCO2 is gradually raised from normocapnic values (40 mmHg) to hypercapnic values (50 and 60 mmHg). CBF is continuously measured during this intervention. Patients are clinically and radiologically followed for 6 months.
Time Frame
For an average of two weeks after aSAH
Secondary Outcome Measure Information:
Title
Cerebral oxygen saturation
Description
Oxygen saturation by NIRS is measured continuously for 2 weeks after aSAH.
Time Frame
For an average of two weeks after aSAH
Title
intracranial pressure (ICP)
Description
ICP is continuously measured by an external ventricular drainage throughout the intervention period.
Time Frame
For an average of two weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Thomas Westermaier, MD
Organizational Affiliation
Department of Neurosurgery, University of Wuerzburg, Germany
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Ekkehard Kunze, MD
Organizational Affiliation
Department of Neurosurgery, University of Wuerzburg
Official's Role
Study Director
Facility Information:
Facility Name
Department of Neurosurgery, University of Wuerzburg
City
Wuerzburg
State/Province
Bavaria
ZIP/Postal Code
97080
Country
Germany
12. IPD Sharing Statement
Citations:
PubMed Identifier
34083595
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.
Results Reference
derived
PubMed Identifier
25148012
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.
Results Reference
derived
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Hypercapnia to Prevent Secondary Ischemia in SAH
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