Cerebral IschemiaPhase 3NCT00841633
Induced Hypertension for Delayed Cerebral Ischaemia After Aneurysmal Subarachnoid Haemorrhage:a Feasibility Study
A Phase 3 study testing Induced hypertension with norepinephrine in people with Cerebral Ischemia and Subarachnoid Hemorrhage, run by UMC Utrecht at 1 site in Netherlands.
Trial summary
The purpose of this study is to test the feasibility of a trial on induced hypertension to improve neurological outcome in patients with subarachnoid haemorrhage that developed the serious complication "delayed cerebral ischemia", and to assess whether induced hypertension results in improved cerebral blood flow (CBF)… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Cerebral Ischemia, Subarachnoid Hemorrhage
- What is being tested?
- Induced hypertension with norepinephrine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 15 participants
- Where
- 1 siteNetherlands
- Study dates
- Feb 2009to Apr 2011
- Phase
- Phase 3
- 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
- Admission to the UMC Utrecht.
- Age 18 years or over.
- Aneurysmal SAH, demonstrated on CT-angiography or cerebral angiography, with onset less than 72 hours before admission.
- A level of consciousness corresponding to a Glasgow Coma Sum Score above 8, as in patients with lower Glasgow Coma Sum Scores, assessment of further deterioration may be less reliable.
Who cannot join
- Symptomatic aneurysm not yet treated by coiling or clipping. Co-existing asymptomatic cerebral aneurysms are no reason for exclusion, since previous studies found no increased risk of rupture of such aneurysms during hypertensive and hypervolemic treatment.(26)
- Co-existing severe head injury.
- A history of a cardiac rhythm disorder, necessitating medical treatment.
- A history of a left ventricular pump failure, necessitating medical treatment.
- Pregnancy.
- Known allergy for CT-contrast agents.
- Renal failure, defined as a serum creatinine > 150 µmol/l, because of the risk of contrast nephropathy.
Trial locations and contacts
1 site in 1 country.
About this study
The purpose of this study is to test the feasibility of a trial on induced hypertension to improve neurological outcome in patients with subarachnoid haemorrhage that developed the serious complication "delayed cerebral ischemia", and to assess whether induced hypertension results in improved cerebral blood flow (CBF) as measured by means of perfusion-CT.
Read the detailed description
Background:
Delayed cerebral ischaemia (DCI) is a major complication after aneurysmal subarachnoid haemorrhage (SAH). The proportion of SAH patients who develop DCI is around 30%. Many centres around the world use induced hypertension, alone or in combination with haemodilution and hypervolaemia, so called Triple-H, as standard therapy in the treatment of DCI, but the efficacy of induced hypertension in reducing DCI is based on case series only, and not on a randomised clinical trial.
Objective:
To test the feasibility of a trial on induced hypertension to improve neurological outcome, and to assess whether induced hypertension results in improved cerebral blood flow (CBF) as measured by means of perfusion-CT.
Study design:
A randomised controlled feasibility trial.
Study population:
Patients admitted to the UMC Utrecht after recent SAH, who develop DCI. Twenty four patients will be randomised into a standard care group or one of the intervention groups.
Interventions:
Patients in the intervention groups are treated with induced hypertension (30 mmHg increase in mean arterial pressure) in order to improve CBF. Patients in the standard care group are treated according to the standardised SAH treatment protocol of the UMC Utrecht by monitoring mean arterial pressure and preventing dropping of mean arterial pressure to under 80 mmHg. 24-36 hours after instalment of the treatment, a perfusion CT scan is performed. In patients that do not show any neurological improvement within 24 hours after starting the hypertensive treatment, the administration of norepinephrine will be tapered. In patients who show improvement, induced hypertension will be continued for a total period of 72 hours, after which norepinephrine will be gradually tapered. Measurement of CBF is performed in all participants with perfusion CT-scanning of the brain at the beginning of the study (as part of regular patient care) and after 24-36 hours after starting .
Main outcome measurement:
The number of patients with the diagnosis of DCI after SAH, in which the intervention (induced hypertension) was adequately performed, included within 18 months after the start of the study.
- Conditions
- Cerebral Ischemia, Subarachnoid Hemorrhage
- Being tested
- Induced hypertension with norepinephrine
- Keywords
- subarachnoid hemorrhage, ischemia, vasospasm, CT, perfusion, induced hypertension, delayed cerebral ischemia
- Medical subject headings
- Brain Ischemia, Subarachnoid Hemorrhage, Ischemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Induced hypertension with norepinephrineDrug
Hypertension will be induced with norepinephrine. Administration of norepinephrine results in vasoconstriction, leading to an increase in blood pressure. The normal blood pressure of the patient will be calculated as the average MAP of the day before the start of the study. To achieve the intended hypertension (30 mmHg above the normal MAP for patients allocated to index group 2) in most cases a dose of 100-300 ng/kg/minute must be administered. Norepinephrine will be started on a dose of 100 ng/kg/minute, after which the dosing will be adjusted to achieve the desired blood pressure level. The maximum dose to be used in the study is 1000 ng/kg/minute. Norepinephrine is administered through the central venous catheter.
| Study group | Role | What they receive |
|---|---|---|
| 1 | No intervention | No induced hypertension (reference group) |
| 2 | Experimental | Induced hypertension with a MAP of 30 mmHg above the average MAP on the previous day; during 24-36 hours, until a perfusion CT scan has been performed Receives: Drug: Induced hypertension with norepinephrine |
What is being measured
The primary outcome is the main question the study is designed to answer.
The main study parameter will be the number of SAH patients with a diagnosis of DCI who were randomised to one of the intervention groups, in whom the intervention was adequately performed, during the duration of the trial.
Measured: duration of the trial
Secondary outcomes (1)
Related to the inclusion, to the influence on cerebral haemodynamics, to the neurological condition and to adverse events
Measured: cerebral haemodynamics: 24-36 hours, neurological condition: 6 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Feb 2009 (estimated)
- Study startFeb 2009
- Primary completionApr 2011
- Study completionApr 2011
Why it stopped: Our RCT recently started. The RCT is similar to the feasibility trial, so it was terminated to avoid 2 trials running simultaniously.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Cerebral IschemiaStudies of the same condition, open and under way.
- More trials run by UMC UtrechtThe sponsor's other registered studies.
- 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 15 participants (actual)
Sponsor and investigators
- Lead sponsor
- UMC Utrecht
- Sponsor type
- University, hospital or other
- Collaborators
- Netherlands Organisation for Scientific Research
- Responsible party
- Principal investigator, A.J.C. Slooter, UMC Utrecht
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00841633
- Sponsor's protocol ID
- 08-137
- Status last verified
- Oct 2011
- First submitted
- 10 Oct 2008
- Last updated
- 12 Oct 2011
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 12 Oct 2011. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Induced Hypertension for Delayed Cerebral Ischaemia After Aneurysmal Subarachnoid Haemorrhage:a Feasibility Study
- ClinicalTrials.gov ID
- NCT00841633
- Acronym / sponsor ID
- 08-137
- Conditions
- Cerebral Ischemia, Subarachnoid Hemorrhage
- Keywords
- subarachnoid hemorrhage, ischemia, vasospasm, CT, perfusion, induced hypertension, delayed cerebral ischemia
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Our RCT recently started. The RCT is similar to the feasibility trial, so it was terminated to avoid 2 trials running simultaniously.
- Enrolment
- 15 participants (actual)
- Lead sponsor
- UMC UtrechtUniversity, hospital or other
- Collaborators
- Netherlands Organisation for Scientific Research
- Study start
- Feb 2009
- Primary completion
- Apr 2011 (actual)
- Study completion
- Apr 2011 (actual)
- First posted
- 11 Feb 2009 (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.
The purpose of this study is to test the feasibility of a trial on induced hypertension to improve neurological outcome in patients with subarachnoid haemorrhage that developed the serious complication "delayed cerebral ischemia", and to assess whether induced hypertension results in improved cerebral blood flow (CBF) as measured by means of perfusion-CT.
Detailed description
Background:
Delayed cerebral ischaemia (DCI) is a major complication after aneurysmal subarachnoid haemorrhage (SAH). The proportion of SAH patients who develop DCI is around 30%. Many centres around the world use induced hypertension, alone or in combination with haemodilution and hypervolaemia, so called Triple-H, as standard therapy in the treatment of DCI, but the efficacy of induced hypertension in reducing DCI is based on case series only, and not on a randomised clinical trial.
Objective:
To test the feasibility of a trial on induced hypertension to improve neurological outcome, and to assess whether induced hypertension results in improved cerebral blood flow (CBF) as measured by means of perfusion-CT.
Study design:
A randomised controlled feasibility trial.
Study population:
Patients admitted to the UMC Utrecht after recent SAH, who develop DCI. Twenty four patients will be randomised into a standard care group or one of the intervention groups.
Interventions:
Patients in the intervention groups are treated with induced hypertension (30 mmHg increase in mean arterial pressure) in order to improve CBF. Patients in the standard care group are treated according to the standardised SAH treatment protocol of the UMC Utrecht by monitoring mean arterial pressure and preventing dropping of mean arterial pressure to under 80 mmHg. 24-36 hours after instalment of the treatment, a perfusion CT scan is performed. In patients that do not show any neurological improvement within 24 hours after starting the hypertensive treatment, the administration of norepinephrine will be tapered. In patients who show improvement, induced hypertension will be continued for a total period of 72 hours, after which norepinephrine will be gradually tapered. Measurement of CBF is performed in all participants with perfusion CT-scanning of the brain at the beginning of the study (as part of regular patient care) and after 24-36 hours after starting .
Main outcome measurement:
The number of patients with the diagnosis of DCI after SAH, in which the intervention (induced hypertension) was adequately performed, included within 18 months after the start of the study.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1 | No intervention | –No induced hypertension (reference group) |
| 2 | Experimental | Drug: Induced hypertension with norepinephrineInduced hypertension with a MAP of 30 mmHg above the average MAP on the previous day; during 24-36 hours, until a perfusion CT scan has been performed |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Admission to the UMC Utrecht.
- Age 18 years or over.
- Aneurysmal SAH, demonstrated on CT-angiography or cerebral angiography, with onset less than 72 hours before admission.
- A level of consciousness corresponding to a Glasgow Coma Sum Score above 8, as in patients with lower Glasgow Coma Sum Scores, assessment of further deterioration may be less reliable.
Key exclusion criteria (7 listed)
- Symptomatic aneurysm not yet treated by coiling or clipping. Co-existing asymptomatic cerebral aneurysms are no reason for exclusion, since previous studies found no increased risk of rupture of such aneurysms during hypertensive and hypervolemic treatment.(26)
- Co-existing severe head injury.
- A history of a cardiac rhythm disorder, necessitating medical treatment.
- A history of a left ventricular pump failure, necessitating medical treatment.
- Pregnancy.
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 |
|---|---|---|
| Induced hypertension with norepinephrineHypertension will be induced with norepinephrine. Administration of norepinephrine results in vasoconstriction, leading to an increase in blood pressure. The normal blood pressure of the patient will be calculated as the average MAP of the day before the start of the study. To achieve the intended hypertension (30 mmHg above the normal MAP for patients allocated to index group 2) in most cases a dose of 100-300 ng/kg/minute must be administered. Norepinephrine will be started on a dose of 100 ng/kg/minute, after which the dosing will be adjusted to achieve the desired blood pressure level. The maximum dose to be used in the study is 1000 ng/kg/minute. Norepinephrine is administered through the central venous catheter. | Drug | 2 |
Primary outcome
The main study parameter will be the number of SAH patients with a diagnosis of DCI who were randomised to one of the intervention groups, in whom the intervention was adequately performed, during the duration of the trial.
Time frame: duration of the trial
1 secondary outcome
Related to the inclusion, to the influence on cerebral haemodynamics, to the neurological condition and to adverse events
Time frame: cerebral haemodynamics: 24-36 hours, neurological condition: 6 weeks
Results and safety
The study was stopped early (reason given: Our RCT recently started. The RCT is similar to the feasibility trial, so it was terminated to avoid 2 trials running simultaniously.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Oct 2011.
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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.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Induced hypertension with norepinephrine in people with Cerebral Ischemia and Subarachnoid Hemorrhage, run by UMC Utrecht at 1 site in Netherlands.
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 4 inclusion and 7 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: stopped early, as of the sponsor's last update on 12 Oct 2011. 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 Netherlands. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
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 was stopped early (reason given: Our RCT recently started. The RCT is similar to the feasibility trial, so it was terminated to avoid 2 trials running simultaniously.). Results are not available in the source record.
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?
The main study parameter will be the number of SAH patients with a diagnosis of DCI who were randomised to one of the intervention groups, in whom the intervention was adequately performed, during the duration of the trial. (time frame: duration of the trial). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 12 Oct 2011.