Hypercapnia to Prevent Secondary Ischemia in SAH

Aneurysmal Subarachnoid Hemorrhage Clinical Trial

— SAHCO2  

Official title:

Therapeutical Hypercapnia to Prevent Secondary Ischemic Events in Aneurysmal Subarachnoid Hemorrhage (aSAH)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01799525
• Other study ID #: WUE102/12
• Status: Completed
• Phase: Phase 1
• First received: February 20, 2013
• Last updated: December 9, 2014
• Start date: January 2013
• Est. completion date: August 2014

Study information

• Verified date: December 2014
• Source: Wuerzburg University Hospital
• Contact: n/a
• Is FDA regulated: No
• Health authority: Germany: Federal Institute for Drugs and Medical Devices
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 10
• Est. completion date: August 2014
• Est. primary completion date: February 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Single Blind (Subject), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Aneurysmal Subarachnoid Hemorrhage
• Hemorrhage
• Hypercapnia
• Subarachnoid Hemorrhage

Intervention

Procedure:
• Hypercapnia by reduction of respiratory volume
By reduction of the respiratory volume, PaCO2 is raised while paO2 is kept constant by modulation of the oxygen supply through the respirator,

Locations

Country	Name	City	State
Germany	Department of Neurosurgery, University of Wuerzburg	Wuerzburg	Bavaria

Sponsors (1)

Lead Sponsor	Collaborator
Wuerzburg University Hospital

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	For an average of two weeks after aSAH	No
Secondary	Cerebral oxygen saturation	Oxygen saturation by NIRS is measured continuously for 2 weeks after aSAH.	For an average of two weeks after aSAH	No
Secondary	intracranial pressure (ICP)	ICP is continuously measured by an external ventricular drainage throughout the intervention period.	For an average of two weeks	Yes