Aneurysmal Subarachnoid HemorrhagePhase 1SAHCO2NCT01799525
Hypercapnia to Prevent Secondary Ischemia in SAH
A Phase 1 study testing Hypercapnia by reduction of respiratory volume in people with Aneurysmal Subarachnoid Hemorrhage, run by Wuerzburg University Hospital at 1 site in Germany.
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Aneurysmal Subarachnoid Hemorrhage
- What is being tested?
- Hypercapnia by reduction of respiratory volume
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 10 participants
- Where
- 1 siteGermany
- Study dates
- Jan 2013to Aug 2014
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- aneurysmal SAH
- SAH Hunt/Hess Grade 3-5
- SAH Fisher Grade 2-4
- Mechanically ventilated
- external ventricular drainage/ICP measurement
Who cannot join
- Age under 18
- ICP > 25 mmHg for > 2 minutes
- pH < 7.250
Trial locations and contacts
1 site in 1 country.
Germany1 site
Department of Neurosurgery, University of Wuerzburg
Würzburg, Bavaria, 97080
About this study
Official title: Therapeutical Hypercapnia to Prevent Secondary Ischemic Events in Aneurysmal Subarachnoid Hemorrhage (aSAH)
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.
Read the 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.
- Conditions
- Aneurysmal Subarachnoid Hemorrhage
- Being tested
- Hypercapnia by reduction of respiratory volume
- Keywords
- Aneurysm, subarachnoid hemorrhage, vasospasm, cerebral ischemia, stroke
- Medical subject headings
- Subarachnoid Hemorrhage, Aneurysm, Brain Ischemia, Stroke
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Hypercapnia by reduction of respiratory volumeProcedure or surgery
By reduction of the respiratory volume, PaCO2 is raised while paO2 is kept constant by modulation of the oxygen supply through the respirator,
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Procedure: Hypercapnia by reduction of respiratory volume |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: For an average of two weeks after aSAH
Secondary outcomes (2)
Cerebral oxygen saturation
Oxygen saturation by NIRS is measured continuously for 2 weeks after aSAH.
Measured: For an average of two weeks after aSAH
intracranial pressure (ICP)
ICP is continuously measured by an external ventricular drainage throughout the intervention period.
Measured: For an average of two weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Feb 2013 (estimated)
- Study startJan 2013
- Primary completionFeb 2014
- Study completionAug 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Aneurysmal Subarachnoid HemorrhageStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 10 participants (actual)
Sponsor and investigators
- Lead sponsor
- Wuerzburg University Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Dr. Thomas Westermaier, Wuerzburg University Hospital
- Investigators
- Thomas Westermaier, MD, Principal investigator, Department of Neurosurgery, University of Wuerzburg, GermanyEkkehard Kunze, MD, Study director, Department of Neurosurgery, University of Wuerzburg
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01799525
- Sponsor's protocol ID
- WUE102/12
- Acronym
- SAHCO2
- Status last verified
- Dec 2014
- First submitted
- 20 Feb 2013
- Last updated
- 10 Dec 2014
- Results posted
- No
- Data monitoring committee
- Yes
Publications
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.
PubMed 34083595Westermaier 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.
PubMed 25148012
Study at a glance
From the registry record, last updated by the sponsor on 10 Dec 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Therapeutical Hypercapnia to Prevent Secondary Ischemic Events in Aneurysmal Subarachnoid Hemorrhage (aSAH)
- ClinicalTrials.gov ID
- NCT01799525
- Acronym / sponsor ID
- SAHCO2 / WUE102/12
- Conditions
- Aneurysmal Subarachnoid Hemorrhage
- Keywords
- Aneurysm, subarachnoid hemorrhage, vasospasm, cerebral ischemia, stroke
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 10 participants (actual)
- Lead sponsor
- Wuerzburg University HospitalUniversity, hospital or other
- Study start
- Jan 2013
- Primary completion
- Feb 2014 (actual)
- Study completion
- Aug 2014 (actual)
- First posted
- 26 Feb 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- Single blind (participant)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Hypercapnia | Experimental | Procedure: Hypercapnia by reduction of respiratory volumeIntervention: 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- aneurysmal SAH
- SAH Hunt/Hess Grade 3-5
- SAH Fisher Grade 2-4
- Mechanically ventilated
- external ventricular drainage/ICP measurement
Key exclusion criteria (3 listed)
- Age under 18
- ICP > 25 mmHg for > 2 minutes
- pH < 7.250
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Hypercapnia by reduction of respiratory volumeBy reduction of the respiratory volume, PaCO2 is raised while paO2 is kept constant by modulation of the oxygen supply through the respirator, | Procedure or surgery | Hypercapnia |
Primary outcome
Cerebral Blood Flow
Time frame: For an average of two weeks after aSAH
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.
2 secondary outcomes
Cerebral oxygen saturation
Time frame: For an average of two weeks after aSAH
intracranial pressure (ICP)
Time frame: For an average of two weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Dec 2014.
- Derived from this study: PubMed 34083595Stetter 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.
- Derived from this study: PubMed 25148012Westermaier 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Thomas Westermaier, MD principal investigator
Department of Neurosurgery, University of Wuerzburg, Germany
Ekkehard Kunze, MD study director
Department of Neurosurgery, University of Wuerzburg
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Hypercapnia by reduction of respiratory volume in people with Aneurysmal Subarachnoid Hemorrhage, run by Wuerzburg University Hospital at 1 site in Germany.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 10 Dec 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Cerebral Blood Flow (time frame: For an average of two weeks after aSAH). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01799525, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Dec 2014.