Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

New study suggests role for clazosentan in the prevention of cerebral vasospasm after aneurysmal SAH

04.07.2005


Actelion Ltd (SWX: ATLN) announced today that a study published in the July edition of the Journal of Neurosurgery suggests that clazosentan can reduce the number and severity of cases of vasospasm following aneurysmal subarachnoid haemorrhage (SAH).1

Vasospasm occurs 5-14 days following SAH and leads to strokes and neurological deficits that cause significant disability to patients and is a major cause of death. As many as 70% of people who have aneurysmal SAH may have arterial narrowing and even with the most advanced surgical and endovascular advances in securing the aneurysm, the outcomes remain poor with up to 30% developing neurological deficits or dying2.

This Phase IIa study with 34 patients demonstrated that patients given the i.v. endothelin receptor antagonist clazosentan continuously for up to 14 days suffered from significantly fewer and less severe cases of vasospasm compared to placebo. Only 40% of patients treated with clazosentan developed cerebral vasospasm, as diagnosed on angiography, compared to 88% of patients treated with placebo (p=0.008).1



Furthermore, there were fewer patients with new cerebral infarcts in the clazosentan group – 15% versus 44% in the placebo group. Overall the nature and severity of adverse events were comparable between the two treatment groups. Infusions of clazosentan were generally well tolerated, with no clinically relevant effects on blood pressure or other vital signs.1

Dr Peter Vajkoczy, Neurosurgeon at the Department of Neurosurgery, University Hospital, Mannheim, and the main author of the study comments: "While our understanding of cerebral vasospasm has continued to improve, a solution to this challenge is yet to be found. However, these results are certainly promising and it is important that these findings are assessed and confirmed in a larger population to identify how clazosentan may have an impact in clinical practice."

The July edition of JNS also carries an editorial focusing on the clazosentan study. Dr Neal Kassell, Professor and Co-chairman of the Department of Neurological Surgery at the University of Virginia comments: "It is encouraging to finally, after nearly one-half century of futile investigations, be able to introduce into clinical trials an agent that, based on experimental studies, has a real potential for preventing vasospasm and, based on preliminary clinical studies, appears to be without significant side effects (including hypotension), as well as exhibiting a suggestion of efficacy."

Following detailed discussions with regulatory authorities worldwide, the findings of this study have already led to the initiation of a comprehensive Phase IIb/III development programme for clazosentan. A multi-centre, international, double-blind, randomized, placebo-controlled, parallel group, dose-finding study CONSCIOUS-1 (Clazosentan to Overcome Neurological iSChemia and Infarct OccUrring after Subarachnoid hemorrhage) will analyse the efficacy of 3 dose levels of clazosentan in preventing the occurrence of cerebral vasospasm following SAH, assessed by angiography. As a secondary endpoint, the study will also assess the ability of clazosentan to reduce the occurrence of early morbidity/mortality as well as overall safety and tolerability of the drug.

CONSCIOUS-1 is expected to recruit 400 patients in approximately 70 centers in 13 countries worldwide. Study results are expected in the first half of 2006. These results will determine the need, size and duration of a Phase III study.

Two pre-clinical studies suggest impact of clazosentan on endothelin receptors A and B This study follows the publication in the June edition of the JNS of two pre-clinical studies which characterised the inhibitory effect of clazosentan on endothelin A (ETA) receptor mediated contraction and endothelin B (ETB) receptor mediated relaxation.3,4

References:

1. Vajkoczy P, Meyer B, Weidauer S et al. Clazosentan (AXV-034343), a selective endothelin A receptor antagonist, in the prevention of cerebral vasospasm following severe aneurysmal subarachnoid hemorrhage: a randomized, double-blind, placebo-controlled, multicenter, Phase IIa study. Journal of Neurosurgery July 2005. 103, 9-17.
2. Harrod, CG, Bendok BR, Batjer HH et al. Prediction of cerebral vasospasm in patients presenting with aneurysmal subarachnoid hemorrhage: a review. Neurosurgery. April 2005. 56, 633-652.
3. Vatter H, Zimmermann M, Tesanovic V et al. Cerebrovascular characterization of clazosentan, the first nonpeptide endothelin receptor antagonist clinically effective for the treatment of cerebral vasospasm. Part I: Inhibitory effect on endothelinA receptor–mediated contraction. Journal of Neurosurgery. June 2005. 102, 1101-1107.
4. Vatter H, Zimmermann M, Tesanovic V et al Cerebrovascular characterization of clazosentan, the first nonpeptide endothelin receptor antagonist shown to be clinically effective for the treatment of cerebral vasospasm. Part II: Effect on endothelinB receptor–mediated relaxation. Journal of Neurosurgery. June 2005. 102, 1108-1114.
5. Wolf PA. Epidemiology of intracerebral haemorrhage. In: Carlos SK, Louis RC, editors. Intracerebral haemorrhage. United States of America: Butterworth Heinemann, 1996: 23.

Alexa Forbes | EurekAlert!
Further information:
http://www.actelion.com
http://www.packerforbes.com

More articles from Studies and Analyses:

nachricht Multi-year study finds 'hotspots' of ammonia over world's major agricultural areas
17.03.2017 | University of Maryland

nachricht Diabetes Drug May Improve Bone Fat-induced Defects of Fracture Healing
17.03.2017 | Deutsches Institut für Ernährungsforschung Potsdam-Rehbrücke

All articles from Studies and Analyses >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: A Challenging European Research Project to Develop New Tiny Microscopes

The Institute of Semiconductor Technology and the Institute of Physical and Theoretical Chemistry, both members of the Laboratory for Emerging Nanometrology (LENA), at Technische Universität Braunschweig are partners in a new European research project entitled ChipScope, which aims to develop a completely new and extremely small optical microscope capable of observing the interior of living cells in real time. A consortium of 7 partners from 5 countries will tackle this issue with very ambitious objectives during a four-year research program.

To demonstrate the usefulness of this new scientific tool, at the end of the project the developed chip-sized microscope will be used to observe in real-time...

Im Focus: Giant Magnetic Fields in the Universe

Astronomers from Bonn and Tautenburg in Thuringia (Germany) used the 100-m radio telescope at Effelsberg to observe several galaxy clusters. At the edges of these large accumulations of dark matter, stellar systems (galaxies), hot gas, and charged particles, they found magnetic fields that are exceptionally ordered over distances of many million light years. This makes them the most extended magnetic fields in the universe known so far.

The results will be published on March 22 in the journal „Astronomy & Astrophysics“.

Galaxy clusters are the largest gravitationally bound structures in the universe. With a typical extent of about 10 million light years, i.e. 100 times the...

Im Focus: Tracing down linear ubiquitination

Researchers at the Goethe University Frankfurt, together with partners from the University of Tübingen in Germany and Queen Mary University as well as Francis Crick Institute from London (UK) have developed a novel technology to decipher the secret ubiquitin code.

Ubiquitin is a small protein that can be linked to other cellular proteins, thereby controlling and modulating their functions. The attachment occurs in many...

Im Focus: Perovskite edges can be tuned for optoelectronic performance

Layered 2D material improves efficiency for solar cells and LEDs

In the eternal search for next generation high-efficiency solar cells and LEDs, scientists at Los Alamos National Laboratory and their partners are creating...

Im Focus: Polymer-coated silicon nanosheets as alternative to graphene: A perfect team for nanoelectronics

Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are less stable. Now researchers at the Technical University of Munich (TUM) have, for the first time ever, produced a composite material combining silicon nanosheets and a polymer that is both UV-resistant and easy to process. This brings the scientists a significant step closer to industrial applications like flexible displays and photosensors.

Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

International Land Use Symposium ILUS 2017: Call for Abstracts and Registration open

20.03.2017 | Event News

CONNECT 2017: International congress on connective tissue

14.03.2017 | Event News

ICTM Conference: Turbine Construction between Big Data and Additive Manufacturing

07.03.2017 | Event News

 
Latest News

Researchers shoot for success with simulations of laser pulse-material interactions

29.03.2017 | Materials Sciences

Igniting a solar flare in the corona with lower-atmosphere kindling

29.03.2017 | Physics and Astronomy

As sea level rises, much of Honolulu and Waikiki vulnerable to groundwater inundation

29.03.2017 | Earth Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>