NCT01799525

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
10

participants targeted

Target at below P25 for phase_1

Timeline
Completed

Started Jan 2013

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

January 1, 2013

Completed
2 months until next milestone

First Submitted

Initial submission to the registry

February 20, 2013

Completed
6 days until next milestone

First Posted

Study publicly available on registry

February 26, 2013

Completed
11 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

February 1, 2014

Completed
6 months until next milestone

Study Completion

Last participant's last visit for all outcomes

August 1, 2014

Completed
Last Updated

December 10, 2014

Status Verified

December 1, 2014

Enrollment Period

1.1 years

First QC Date

February 20, 2013

Last Update Submit

December 9, 2014

Conditions

Aneurysmal Subarachnoid Hemorrhage

Keywords

Aneurysmsubarachnoid hemorrhagevasospasmcerebral ischemiastroke

Outcome Measures

Primary Outcomes (1)

  • 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

Secondary Outcomes (2)

  • Cerebral oxygen saturation

    For an average of two weeks after aSAH

  • intracranial pressure (ICP)

    For an average of two weeks

Study Arms (1)

Hypercapnia

EXPERIMENTAL

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

Interventions

Hypercapnia by reduction of respiratory volumePROCEDURE

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

Hypercapnia

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Department of Neurosurgery, University of Wuerzburg

Würzburg, Bavaria, 97080, Germany

Location

Related Publications (2)

  • 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.

    PMID: 34083595DERIVED

  • 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.

    PMID: 25148012DERIVED

MeSH Terms

Conditions

Subarachnoid HemorrhageAneurysmBrain IschemiaStroke

Condition Hierarchy (Ancestors)

Intracranial HemorrhagesCerebrovascular DisordersBrain DiseasesCentral Nervous System DiseasesNervous System DiseasesVascular DiseasesCardiovascular DiseasesHemorrhagePathologic ProcessesPathological Conditions, Signs and Symptoms

Study Officials

  • Thomas Westermaier, MD

    Department of Neurosurgery, University of Wuerzburg, Germany

    PRINCIPAL INVESTIGATOR

  • Ekkehard Kunze, MD

    Department of Neurosurgery, University of Wuerzburg

    STUDY DIRECTOR

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NA
Masking
SINGLE
Who Masked
PARTICIPANT
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
MD

Study Record Dates

First Submitted

February 20, 2013

First Posted

February 26, 2013

Study Start

January 1, 2013

Primary Completion

February 1, 2014

Study Completion

August 1, 2014

Last Updated

December 10, 2014

Record last verified: 2014-12

Locations

DE(1)