Aneurysmal Subarachnoid HemorrhagePhase 2REVERSENCT02560532
Evaluation of the Efficacy and Safety of Clazosentan in Reversing Cerebral Vasospasm in Adult Subjects With Aneurysmal Subarachnoid Hemorrhage
A Phase 2 study testing Clazosentan in people with Aneurysmal Subarachnoid Hemorrhage, run by Idorsia Pharmaceuticals Ltd. at 11 sites in 3 countries.
Trial summary
The purpose of this study is to evaluate the safety and potential therapeutic benefit of use of clazosentan in reversing cerebral vasospasm (a narrowing of blood vessels in the brain due to the presence of blood in the space around the brain) in patients who have suffered a condition known as aneurysmal subarachnoid… Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Aneurysmal Subarachnoid Hemorrhage
- What is being tested?
- Clazosentan
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 25 participants
- Where
- 11 sitesin 3 countries
- Study dates
- 1 Mar 2016to 2 May 2017
- Phase
- Phase 2
- 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 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Signed informed consent from the subject or proxy/legal representative
- Aneurysmal subarachnoid hemorrhage (aSAH)confirmed by digital subtraction angiogram (DSA) or computed tomography angiogram (CTA), successfully secured by surgical clipping or endovascular coiling within 72 hours of rupture
- World Federation of Neurological Surgeons (WFNS) grade 1-4 at admission, and which must not increase to grade 5 at the time of enrollment
- Moderate or severe global cerebral vasospasm at the time of enrollment, documented by digital subtraction angiography (DSA) performed not earlier than 48 hours post aneurysm-securing procedure
- Women of childbearing potential must have a negative serum pregnancy test at screening and must use a reliable method of contraception from hospital discharge up to 30 days after discontinuation of study drug infusion, and fertile males must use a condom as a contraceptive method during this same period
Who cannot join
- SAH due to causes other than a saccular aneurysm
- Any moderate or severe cerebral vasospasm on angiography prior to the aneurysm-securing procedure
- Presence of a new or worsened cerebral infarct or evidence of significant bleeding post aneurysm-securing procedure, or re-bleeding, on a CT scan performed within 24 hours prior to enrollment
- Total bilirubin > 2 times the upper limit of normal, and / or a known diagnosis or clinical suspicion of liver cirrhosis or moderate to severe hepatic impairment
- Any severe or unstable concomitant condition or disease (e.g., cancer, hematological, or coronary disease) or chronic condition (e.g., drug abuse, severe alcoholism), which, in the opinion of the investigator, would interfere with the assessment of the safety or effect of the study treatment
Trial locations and contacts
11 sites in 3 countries.
11 sites in 3 countries
France5 sites
Site 1002
Bron, 69677
Site 1006
Clermont-Ferrand, 63003
Site 1004
Marseille, 13385
Site 1005
Montpellier, 34295
Site 1001
Paris, 75013
Switzerland5 sites
Site 3005
Aarau, 5001
Site 3001
Basel, 4031
Site 3003
Bern, 3010
Site 3004
Geneva, 1211
Site 3002
Zurich, 8091
About this study
Official title: A Prospective, Multi-center, Open-label, Single-arm, Phase 2 Study to Assess the Efficacy and Safety of Clazosentan in Reversing Angiographically-confirmed Cerebral Vasospasm in Adult Subjects With Aneurysmal Subarachnoid Hemorrhage (aSAH) Treated by Surgical Clipping or Endovascular Coiling
The purpose of this study is to evaluate the safety and potential therapeutic benefit of use of clazosentan in reversing cerebral vasospasm (a narrowing of blood vessels in the brain due to the presence of blood in the space around the brain) in patients who have suffered a condition known as aneurysmal subarachnoid hemorrhage caused by bleeding onto the surface of the brain from a ruptured brain aneurysm
Read the detailed description
Aneurysmal subarachnoid hemorrhage (aSAH) is characterized by bleeding onto the brain surface due to a rupture of a pouch or bulge in a brain vessel (called an aneurysm). It is a rare but serious condition with a high risk of death. Even patients who have had successful repair of the aneurysm remain at risk for developing cerebral vasospasm, which can result in harmful conditions related to the lack of oxygen to parts of the brain and death. Cerebral vasospasm usually occurs within the first couple of weeks after aSAH, and it is difficult to treat. Currently there is no safe, efficacious and widely available treatment. Previous animal studies have shown that a new drug under investigation, clazosentan, was able to reverse cerebral vasospasm in animal models of SAH. A first trial conducted in a small number of patients showed some benefit of clazosentan in reversing established cerebral vasospasm after aSAH. Clazosentan has already been evaluated in the prevention of cerebral vasospasm in several large clinical trials in aSAH. This current study aims to evaluate if clazosentan is effective and safe in the treatment of cerebral vasospasm after aSAH.
- Conditions
- Aneurysmal Subarachnoid Hemorrhage
- Being tested
- Clazosentan
- Keywords
- aneurysmal subarachnoid hemorrhage, cerebral vasospasm, clazosentan
- Medical subject headings
- Subarachnoid Hemorrhage, Vasospasm, Intracranial
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ClazosentanDrug
Also called ACT-108475
Concentrated solution for intravenous injection
| Study group | Role | What they receive |
|---|---|---|
| Clazosentan | Experimental | Diluted solution administered as a continuous intravenous infusion at a rate of 15 mg/h for up to a cumulative maximum of 10 days Receives: Drug: Clazosentan |
What is being measured
The primary outcome is the main question the study is designed to answer.
Successful reversal of global cerebral vasospasm 3 hours post-study drug initiation
Successful reversal is defined as an improvement in at least one level of severity on the "global vasospasm assessment" (i.e., from severe to moderate, mild, or none, or from moderate to mild or none), evaluated on Digital subtraction angiogram (DSA)
Measured: 3 hours post-study drug initiation
Secondary outcomes (3)
Successful reversal of global cerebral vasospasm 24 hours post-study drug initiation
Measured: 24 hours post-study drug initiation
Maximum change from baseline in angiographic cerebral circulation time (CCT)
CCT will be determined in the left and right anterior circulation, and the posterior circulation, on the digital subtraction angiogram (DSA) at each scheduled time point.
Measured: At baseline, 3 hours and 24 hours post-study drug initiation
Number of subjects with adverse events
An adverse event is defined as any unfavorable and unintended sign, including an abnormal laboratory finding, symptom or disease, that occurs during the course of the study, whether or not considered related to the study drug
Measured: Up to 30 days after study drug discontinuation
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Sep 2015 (estimated)
- Study start1 Mar 2016
- Primary completion2 May 2017
- Study completion2 May 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 25 participants (actual)
Sponsor and investigators
- Lead sponsor
- Idorsia Pharmaceuticals Ltd.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Angelina Marr, BSc. Pharm, Study director, Actelion
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02560532
- Sponsor's protocol ID
- AC-054-203
- Other IDs
- 2015-002721-18, 2015
- Acronym
- REVERSE
- Status last verified
- Jul 2018
- First submitted
- 23 Sep 2015
- Last updated
- 10 Jul 2018
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 10 Jul 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Prospective, Multi-center, Open-label, Single-arm, Phase 2 Study to Assess the Efficacy and Safety of Clazosentan in Reversing Angiographically-confirmed Cerebral Vasospasm in Adult Subjects With Aneurysmal Subarachnoid Hemorrhage (aSAH) Treated by Surgical Clipping or Endovascular Coiling
- ClinicalTrials.gov ID
- NCT02560532
- Acronym / sponsor ID
- REVERSE / AC-054-203
- Conditions
- Aneurysmal Subarachnoid Hemorrhage
- Keywords
- aneurysmal subarachnoid hemorrhage, cerebral vasospasm, clazosentan
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 25 participants (actual)
- Lead sponsor
- Idorsia Pharmaceuticals Ltd.Industry (pharma, biotech, devices)
- Study start
- 1 Mar 2016
- Primary completion
- 2 May 2017 (actual)
- Study completion
- 2 May 2017 (actual)
- First posted
- 25 Sep 2015 (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 evaluate the safety and potential therapeutic benefit of use of clazosentan in reversing cerebral vasospasm (a narrowing of blood vessels in the brain due to the presence of blood in the space around the brain) in patients who have suffered a condition known as aneurysmal subarachnoid hemorrhage caused by bleeding onto the surface of the brain from a ruptured brain aneurysm
Detailed description
Aneurysmal subarachnoid hemorrhage (aSAH) is characterized by bleeding onto the brain surface due to a rupture of a pouch or bulge in a brain vessel (called an aneurysm). It is a rare but serious condition with a high risk of death. Even patients who have had successful repair of the aneurysm remain at risk for developing cerebral vasospasm, which can result in harmful conditions related to the lack of oxygen to parts of the brain and death. Cerebral vasospasm usually occurs within the first couple of weeks after aSAH, and it is difficult to treat. Currently there is no safe, efficacious and widely available treatment. Previous animal studies have shown that a new drug under investigation, clazosentan, was able to reverse cerebral vasospasm in animal models of SAH. A first trial conducted in a small number of patients showed some benefit of clazosentan in reversing established cerebral vasospasm after aSAH. Clazosentan has already been evaluated in the prevention of cerebral vasospasm in several large clinical trials in aSAH. This current study aims to evaluate if clazosentan is effective and safe in the treatment of cerebral vasospasm after aSAH.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Clazosentan | Experimental | Drug: ClazosentanDiluted solution administered as a continuous intravenous infusion at a rate of 15 mg/h for up to a cumulative maximum of 10 days |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Signed informed consent from the subject or proxy/legal representative
- Aneurysmal subarachnoid hemorrhage (aSAH)confirmed by digital subtraction angiogram (DSA) or computed tomography angiogram (CTA), successfully secured by surgical clipping or endovascular coiling within 72 hours of rupture
- World Federation of Neurological Surgeons (WFNS) grade 1-4 at admission, and which must not increase to grade 5 at the time of enrollment
- Moderate or severe global cerebral vasospasm at the time of enrollment, documented by digital subtraction angiography (DSA) performed not earlier than 48 hours post aneurysm-securing procedure
- Women of childbearing potential must have a negative serum pregnancy test at screening and must use a reliable method of contraception from hospital discharge up to 30 days after discontinuation of study drug infusion, and fertile males must use a condom as a contraceptive method during this same period
Key exclusion criteria (5 listed)
- SAH due to causes other than a saccular aneurysm
- Any moderate or severe cerebral vasospasm on angiography prior to the aneurysm-securing procedure
- Presence of a new or worsened cerebral infarct or evidence of significant bleeding post aneurysm-securing procedure, or re-bleeding, on a CT scan performed within 24 hours prior to enrollment
- Total bilirubin > 2 times the upper limit of normal, and / or a known diagnosis or clinical suspicion of liver cirrhosis or moderate to severe hepatic impairment
- Any severe or unstable concomitant condition or disease (e.g., cancer, hematological, or coronary disease) or chronic condition (e.g., drug abuse, severe alcoholism), which, in the opinion of the investigator, would interfere with the assessment of the safety or effect of the study treatment
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 |
|---|---|---|
| ClazosentanAlso: ACT-108475Concentrated solution for intravenous injection | Drug | Clazosentan |
Primary outcome
Successful reversal of global cerebral vasospasm 3 hours post-study drug initiation
Time frame: 3 hours post-study drug initiation
Successful reversal is defined as an improvement in at least one level of severity on the "global vasospasm assessment" (i.e., from severe to moderate, mild, or none, or from moderate to mild or none), evaluated on Digital subtraction angiogram (DSA)
3 secondary outcomes
Successful reversal of global cerebral vasospasm 24 hours post-study drug initiation
Time frame: 24 hours post-study drug initiation
Maximum change from baseline in angiographic cerebral circulation time (CCT)
Time frame: At baseline, 3 hours and 24 hours post-study drug initiation
Number of subjects with adverse events
Time frame: Up to 30 days after study drug discontinuation
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 Jul 2018.
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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.
Angelina Marr, BSc. Pharm study director
Actelion
11 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Clazosentan in people with Aneurysmal Subarachnoid Hemorrhage, run by Idorsia Pharmaceuticals Ltd. at 11 sites in 3 countries.
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 5 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 Jul 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 11 sites in France, Switzerland, Finland. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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?
Successful reversal of global cerebral vasospasm 3 hours post-study drug initiation (time frame: 3 hours post-study drug initiation). 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 10 Jul 2018.