Hypercapnia to Prevent Secondary Ischemia in SAH (SAHCO2)

This study is currently recruiting participants. (see Contacts and Locations)
Verified February 2013 by Wuerzburg University Hospital
Sponsor:
Information provided by (Responsible Party):
Dr. Thomas Westermaier, Wuerzburg University Hospital
ClinicalTrials.gov Identifier:
NCT01799525
First received: February 20, 2013
Last updated: February 23, 2013
Last verified: February 2013
  Purpose

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.


Condition Intervention Phase
Aneurysmal Subarachnoid Hemorrhage
Procedure: Hypercapnia by reduction of respiratory volume
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Single Blind (Subject)
Primary Purpose: Treatment
Official Title: Therapeutical Hypercapnia to Prevent Secondary Ischemic Events in Aneurysmal Subarachnoid Hemorrhage (aSAH)

Resource links provided by NLM:


Further study details as provided by Wuerzburg University Hospital:

Primary Outcome Measures:
  • Cerebral Blood Flow [ Time Frame: For an average of two weeks after aSAH ] [ Designated as safety issue: No ]
    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 [ Time Frame: For an average of two weeks after aSAH ] [ Designated as safety issue: No ]
    Oxygen saturation by NIRS is measured continuously for 2 weeks after aSAH.

  • intracranial pressure (ICP) [ Time Frame: For an average of two weeks ] [ Designated as safety issue: Yes ]
    ICP is continuously measured by an external ventricular drainage throughout the intervention period.


Estimated Enrollment: 10
Study Start Date: January 2013
Estimated Study Completion Date: February 2014
Estimated Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Hypercapnia
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.
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,

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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01799525

Contacts
Contact: Thomas Westermaier, MD +49 931 24527 westermaier.t@nch.uni-wuerzburg.de

Locations
Germany
Department of Neurosurgery, University of Wuerzburg Recruiting
Wuerzburg, Bavaria, Germany, 97080
Contact: Thomas Westermaier, MD    +49 931 201 ext 24527    westermaier.t@nch.uni-wuerzburg   
Sub-Investigator: Christian Stetter, MD         
Sub-Investigator: Ralf Muellenbach, MD         
Sub-Investigator: Nadine Willner, MD         
Sponsors and Collaborators
Wuerzburg University Hospital
Investigators
Principal Investigator: Thomas Westermaier, MD Department of Neurosurgery, University of Wuerzburg, Germany
Study Director: Ekkehard Kunze, MD Department of Neurosurgery, University of Wuerzburg
  More Information

No publications provided

Responsible Party: Dr. Thomas Westermaier, MD, Wuerzburg University Hospital
ClinicalTrials.gov Identifier: NCT01799525     History of Changes
Other Study ID Numbers: WUE102/12
Study First Received: February 20, 2013
Last Updated: February 23, 2013
Health Authority: Germany: Federal Institute for Drugs and Medical Devices

Keywords provided by Wuerzburg University Hospital:
Aneurysm
subarachnoid hemorrhage
vasospasm
cerebral ischemia
stroke

Additional relevant MeSH terms:
Hemorrhage
Hypercapnia
Subarachnoid Hemorrhage
Pathologic Processes
Signs and Symptoms, Respiratory
Signs and Symptoms
Intracranial Hemorrhages
Cerebrovascular Disorders
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Vascular Diseases
Cardiovascular Diseases

ClinicalTrials.gov processed this record on August 28, 2014