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Trial record 3 of 7 for:    clazosentan | idorsia [Lead]

Clinical Research Study With Clazosentan to Evaluate Its Effects on Preventing Complications Due to the Narrowing of the Blood Vessels (Vasospasm) in the Brain, Caused by Bleeding Onto the Surface of the Brain (REACT)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03585270
Recruitment Status : Recruiting
First Posted : July 12, 2018
Last Update Posted : July 24, 2020
Sponsor:
Information provided by (Responsible Party):
Idorsia Pharmaceuticals Ltd.

Brief Summary:
This study will evaluate if clazosentan (on top of normal routine medical care) can reduce the risk of developing complications related to cerebral vasospasm and permanent brain damage as compared to normal routine medical care alone.

Condition or disease Intervention/treatment Phase
Aneurysmal Subarachnoid Hemorrhage Drug: Clazosentan Drug: Placebo Phase 3

Detailed Description:

When a blood vessel just outside the brain bursts and causes bleeding onto its surface, the space surrounding the brain (the subarachnoid space) fills with blood. This condition is called subarachnoid hemorrhage. The bleeding due to the rupture of a pouch-like structure or a bulge (called an aneurysm) that formed on one of the blood vessels is condition called aneurysmal subarachnoid hemorrhage (aSAH).

In this study, clazosentan is being tested against normal routine medical care to determine if clazosentan can reduce the risk of developing complications related to vasospasm and permanent brain damage.

Participation will last for approximately 6 months from the episode of bleeding. For subjects randomized in the high-risk prevention group, treatment will start within 96 hours following the time of the aneurysm rupture, and be administered where possible, for 14 days. For subjects randomized in the early treatment group, treatment must begin within 24 hours of the time of the angiogram documenting the cerebral vasospasm necessary for entry into the study. Treatment will be administered for a minimum of 6 days and a maximum of 14 days.

The end-of-study will be conducted as a telephone interview 6 months after the episode of bleeding.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 400 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description: This study will be performed in a double-blind fashion. The investigator, study personnel, subjects, clinical research associates (CRAs), sponsor personnel, and vendor / Contract Research Organization (CRO) personnel involved in the conduct of the study will remain blinded to the study treatment received by the subjects during the double-blind treatment period until study closure
Primary Purpose: Prevention
Official Title: A Prospective, Multi-center, Double-blind, Randomized, Placebo-controlled, Parallel-group, Phase 3 Study to Assess the Efficacy and Safety of Clazosentan in Preventing Clinical Deterioration Due to Delayed Cerebral Ischemia (DCI), in Adult Subjects With Aneurysmal Subarachnoid Hemorrhage (aSAH)
Actual Study Start Date : December 15, 2018
Estimated Primary Completion Date : May 2021
Estimated Study Completion Date : October 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Bleeding

Arm Intervention/treatment
Experimental: Clazosentan
Participants will receive clazosentan for up to 14 days, followed by a safety follow-up period of 24 hours, and an extended follow-up period to the end-of-study visit at Week 24 post aneurysmal subarachnoid hemorrhage (aSAH).
Drug: Clazosentan
Clazosentan will be administered as a continuous intravenous infusion at the dose of 15 mg/hour for up to 14 days.
Other Name: ACT-108475

Placebo Comparator: Placebo
Participants will receive clazosentan matching-placebo for up to 14 days, followed by a safety follow-up period of 24 hours, and an extended follow-up period to the end-of-study visit at Week 24 post aneurysmal subarachnoid hemorrhage (aSAH).
Drug: Placebo
Placebo will be administered at the same infusion rate as clazosentan for up to 14 days.




Primary Outcome Measures :
  1. Occurrence of clinical deterioration due to delayed cerebral ischemia (DCI) from study drug initiation up to 14 days post-study drug initiation [ Time Frame: Up to 14 days post-study drug initiation ]
    Clinical deterioration due to DCI is defined as a worsening of at least 2 points compared to the reference score, on the mGCS or the aNIHSS, lasting for at least 2 hours, which cannot be entirely attributed to causes other than cerebral vasospasm. It is centrally adjudicated by the CEC based on a written charter and review of clinical data, case narratives, angiograms and CT scans


Secondary Outcome Measures :
  1. Occurrence of all-cause new or worsened cerebral infarction* ≥ 5 cm3 (total volume) at Day 16 post-study drug initiation [ Time Frame: At Day 16 post study drug initiation ]
    New or worsened infarcts are determined by central radiology review comparing the CT scan performed 16 days after study drug initiation with the CT scan performed just prior to randomization.

  2. Long-term clinical outcome assessed by the Glasgow Outcome Scale Extended (GOSE) at Week 12 post-aSAH, dichotomized as follows: poor outcome (score ≤ 4) and good outcome (score > 4) [ Time Frame: At Week 12 post-aSAH ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Written informed consent to participate in the study must be obtained from the subject or proxy/legal representative at any time from hospital admission to prior to initiation of any study-mandated procedure,
  • Males and females aged 18 to 70 years (inclusive, at hospital admission),
  • Subjects with a ruptured saccular aneurysm, angiographically confirmed by DSA or CTA, which has been successfully secured within 72 hours of rupture, by surgical clipping or endovascular coiling,
  • WFNS (World Federation of Neurosurgical Societies) grades 1-4 (based on Glasgow Coma Scale [GCS]) assessed after recovery from the aneurysm-securing procedure and after external ventricular drainage for hydrocephalus, if required,
  • Subjects must meet one of the two following inclusion criteria:

    • High-risk prevention: Subjects with a "thick and diffuse clot" (thick and diffuse is defined as a thick confluent clot, more than 4 mm in thickness, involving 3 or more basal cisterns) on the hospital admission CT scan, absence of cerebral vasospasm at the time of randomization, and possibility to start study drug in the ICU (or equivalent environment where all protocol assessments can be performed and the Patient Management Guidelines followed), within 96 hours after the time of the aneurysm rupture, OR
    • Early treatment: Subjects without a thick and diffuse clot on the hospital admission CT scan who develop asymptomatic or minimally symptomatic moderate to severe angiographic vasospasm, within the 14-day period post-aneurysm rupture, and for whom it is possible to start study drug in the ICU (or equivalent environment where all protocol assessments can be performed and the Patient Management Guidelines followed), within 24 hours of this angiographic diagnosis,
  • Presence of a cerebral CT scan performed at least 8 hours post-aneurysm-securing procedure and within 24 hours prior to randomization
  • Absence of a significant new or worsened cerebral infarct or re-bleeding of the repaired aneurysm on the post-procedure CT scan.
  • A woman of childbearing potential is eligible only if the pregnancy test performed during the screening period is negative. Agreement must be obtained to take the necessary precautions to avoid pregnancy from hospital discharge until 30 days post-study drug discontinuation. If breastfeeding, agreement must be obtained to refrain for the duration of the treatment with study drug and until 30 days post-study drug discontinuation.
  • Males are eligible for study participation only if they agree to take the necessary precautions to avoid pregnancy in a female partner from hospital discharge until 30 days post-study drug discontinuation.

Exclusion Criteria:

  • Aneurysmal subarachnoid hemorrhage (aSAH), aneurysm-securing procedure, vasospasm:

    • Subjects with SAH due to causes other than a saccular aneurysm (e.g., trauma or rupture of fusiform or mycotic aneurysms, SAH associated with arterio-venous malformation, vertebral dissections),
    • Significant bleeding post aneurysm-securing procedure (e.g., due to intra-ventricular drain, intra-cerebral hemorrhage, epidural hematoma, vessel dissection or rupture, re-bleeding of the repaired aneurysm), based on investigator judgment,
    • Intra-or peri-aneurysm securing procedure complication requiring non-routine medical or interventional treatment such as administration of an antithrombotic or anti-platelet agent (e.g., abciximab), which is not completely resolved prior to randomization,
    • Intraventricular hemorrhage on the hospital admission CT scan, filling more than 50% of both lateral ventricles and with involvement of the 3rd and 4th ventricles.
    • Intracerebral hemorrhage on the hospital admission CT scan, with an approximate volume of > 50 mL,
    • Presence of cerebral vasospasm at hospital admission (initial admission or transfer from another hospital) believed to be associated with a prior bleed (i.e., occurring before the bleed for which the subject is currently hospitalized). Vasospasm occurring during the aneurysm securing procedure is not an exclusion criterion,
  • Neurological and functional status:

    • Subjects with a new major neurological deficit occurring post aneurysm-securing procedure which is attributable to the procedure and does not improve to pre-procedure status before randomization,
    • Subjects with a GCS score of ≤ 9 at the time of randomization and without intracranial pressure (ICP) monitoring,
    • Modified Rankin Score of 3 or higher, prior to the aSAH (i.e., due to a chronic condition),
  • Other clinical considerations:

    • Subjects with 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,
    • Hypotension (systolic blood pressure [SBP] ≤ 90 mmHg) at time of randomization that is refractory to treatment,
    • Unresolved pulmonary edema or significant pneumonia still present at the time of randomization, or severe hypoxia at the time of randomization in intubated subjects, defined as PaO2/FiO2 ≤ 200,
    • High sustained ICP (> 25 mmHg lasting > 20 minutes) at time of randomization, despite optimal treatment, in subjects with ICP monitoring,
    • Severe cardiac failure requiring inotropic support at the time of random

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03585270


Contacts
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Contact: Clinical Trial Disclosure desk +18566613721 clinical-trials-disclosure@idorsia.com

Locations
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United States, California
Stanford Hospital & Clinics - Stanford School of Medicine Dept. of Neurosurgery Not yet recruiting
Stanford, California, United States, 94305
United States, Florida
Baptist Health Jacksonville Not yet recruiting
Jacksonville, Florida, United States, 32207
Mayo clinic, Dept of Neurosurgery Not yet recruiting
Jacksonville, Florida, United States, 32224
United States, Illinois
University of Illinois - Department of Neurosurgery Active, not recruiting
Chicago, Illinois, United States, 60612
United States, Maryland
University of Maryland Medical Systems - Neurosurgery Active, not recruiting
Baltimore, Maryland, United States, 21201
United States, Massachusetts
Boston University School of Medicine / Boston University Medical Center Active, not recruiting
Boston, Massachusetts, United States, 02118
Beth Israel Deaconess Medical Center Dept of Neurosurgery Not yet recruiting
Boston, Massachusetts, United States, 02215
United States, Michigan
Henry Ford Health System Withdrawn
Detroit, Michigan, United States, 48202
United States, Missouri
Washington University - Dept. of Neurosurgery Not yet recruiting
Saint Louis, Missouri, United States, 63110
United States, New York
Northwell Health, Department of Neurosurgery Not yet recruiting
Manhasset, New York, United States, 11030
Mt Sinai Hospital Not yet recruiting
New York, New York, United States, 10029
Columbia University Medical Center Dept. of Neurology - Neurological Intensive Care Unit Not yet recruiting
New York, New York, United States, 10032
United States, Ohio
University of Cincinnati, Neurosurgery Not yet recruiting
Cincinnati, Ohio, United States, 45267
University Hospitals Case Medical Center - Department of Neurosurgery Active, not recruiting
Cleveland, Ohio, United States, 44106
The Ohio State University -Wexner Medical Center Active, not recruiting
Columbus, Ohio, United States, 43210
United States, Oklahoma
Oklahoma University Health Sciences Center - Department of Neurology Active, not recruiting
Oklahoma City, Oklahoma, United States, 73104
United States, Oregon
Oregon Health and Science University Active, not recruiting
Portland, Oregon, United States, 97239
United States, Pennsylvania
Penn State Milton S Hershey Medical Center, Neurosurgery Active, not recruiting
Hershey, Pennsylvania, United States, 17033
Thomas Jefferson University School of Medicine Dept. of Neurosurgery Withdrawn
Philadelphia, Pennsylvania, United States, 19107
Temple University Hospital - Lung Center Not yet recruiting
Philadelphia, Pennsylvania, United States, 19140
Albert Einstein Medical Center Dept of Neurology Withdrawn
Philadelphia, Pennsylvania, United States, 19141
United States, Tennessee
Vanderbilt University Medical Center - Department of Neurosurgery Recruiting
Nashville, Tennessee, United States, 37232
United States, Virginia
Virginia Commonwealth University, Department of Neurosurgery Not yet recruiting
Richmond, Virginia, United States, 23298
Austria
Medizinische Universität Innsbruck; Universitätsklinik für Neurologie und Psychiatrie Recruiting
Innsbruck, Austria, 6020
Kepler Universitätsklinikum, Universitätsklinik für Neurochirurgie Recruiting
Linz, Austria, A-4020
Belgium
Hospital Erasme, Service de Soins Intensifs Recruiting
Brussels, Belgium, 1070
Hospital - Cliniques Universitaires Saint-Luc, Service de Neurochirurgie Recruiting
Brussels, Belgium, 1200
Ziekenhuis Oost-Limburg Withdrawn
Genk, Belgium, 3600
Neurology Department, University Hospital Recruiting
Gent, Belgium, 9000
Hospital UZ Leuven, Neurosurgery Department Recruiting
Leuven, Belgium, 3000
University Hospital Sart Tilman Liege Not yet recruiting
Liège, Belgium, 4000
Canada, Alberta
University of Calgary & Foothills Medical Centre Withdrawn
Calgary, Alberta, Canada, T2N 4N1
University of Alberta Hospital Department of Neurological Surgery Active, not recruiting
Edmonton, Alberta, Canada, T6G 2B7
Canada, British Columbia
Vancouver General Hospital Neurology Withdrawn
Vancouver, British Columbia, Canada, V5Z 1M9
Canada, Manitoba
Winnipeg Regional Health Authority Health Sciences Centre Active, not recruiting
Winnipeg, Manitoba, Canada, R3A 1R9
Canada, Nova Scotia
Halifax Infirmary, Nova Scotia Health Authority Active, not recruiting
Halifax, Nova Scotia, Canada, B3H 3A7
Canada, Saskatchewan
Royal University Hospital Department of Neurology Active, not recruiting
Saskatoon, Saskatchewan, Canada, S7N 0W8
Czechia
Fakultní nemocnice Brno Neurochirurgická klinika Recruiting
Brno, Czechia, 62500
"Fakultní nemocnice Hradec Králové Neurochirurgická klinika" Not yet recruiting
Hradec Králové, Czechia, 50005
Fakultní nemocnice Ostrava Neurochirurgická klinika Recruiting
Ostrava-Poruba, Czechia, 70852
University Hospital in Pilsen, Department of Neurosurgery Recruiting
Plzen, Czechia, 30460
Ústřední vojenská nemocnice Praha Neurochirurgická klinika Active, not recruiting
Praha, Czechia, 16902
Masarykova nemocnice v Ústí nad Labem Neurochirurgie Active, not recruiting
Ústí Nad Labem, Czechia, 40113
Denmark
Aalborg Neurosurgery Active, not recruiting
Aalborg, Denmark, 9100
Odense Universitets Hospital Neurokirurgisk afdelning Active, not recruiting
Odense, Denmark, 5000
Finland
Helsingin yliopistollinen keskussairaala Neurokirurgian klinikka Active, not recruiting
Helsinki, Finland, 00260
Kuopio University Hospital Active, not recruiting
Kuopio, Finland, 70210
Tampereen yliopistollinen sairaala Neurokirurgian klinika Active, not recruiting
Tampere, Finland, 33520
Turku University Hospital Neurosurgery, T-hospital Recruiting
Turku, Finland, 20520
France
Hôpital neurologique Pierre Wertheimer Service de Reanimation Recruiting
Bron, France, 69006
Hôpital Gabriel Montpied, ICU DEPT, Neuro reanimation departement Not yet recruiting
Clermont-Ferrand, France, 63003
Hôpital de la Timone 2, Intensive Care Unit SAR 1 Active, not recruiting
Marseille, France, 13385
Hôpital Gui de CHAULIAC Active, not recruiting
Montpellier, France, 34295
Hospital Lariboisiere Paris Active, not recruiting
Paris, France, 75010
Hôpital Pitié-Salpêtrière, Service de neuroréanimation chirurgicale Babinski Active, not recruiting
Paris, France, 75013
CHRU Reims Hopital Maison Blanche Not yet recruiting
Reims, France, 51100
CHU Rennes, Pontchaillou Active, not recruiting
Rennes, France, 35033
Univ Hosp Toulouse, University Hospital Purpan Pierre Paul Riquet Hospital Active, not recruiting
Toulouse, France, 31059
Germany
Klinik für Diagnostische Radiologie und Neuroradiologie, Augsburg Recruiting
Augsburg, Germany, 86156
Charite Universitätsmedizin Berlin - Klinik und Poliklinik für Neurochirurgie Active, not recruiting
Berlin, Germany, 10117
Heinrich-Heine Universität Düsseldorf -Klinik für Neurochirugie Active, not recruiting
Düsseldorf, Germany, 40225
University of Erlangen-Nürnberg, Dpt. of Neurosurgery Recruiting
Erlangen, Germany, 91054
University Hospital of Essen, Department of Neurosurgery Recruiting
Essen, Germany, 45147
Universitätsklinik Frankfurt, Klinik und Poliklinik für Neurochirurgie, Dept of neurosurgery Recruiting
Frankfurt, Germany, 60528
Bezirkskrankenhaus Günzburg - Klinik für Neurochirugie Recruiting
Günzburg, Germany, 89132
Asklepios Klinik St. Georg - Neurochirugie Active, not recruiting
Hamburg, Germany, 20099
University Hospital of Hamburg-Eppendorf, Dpt. of Neurosurgery Not yet recruiting
Hamburg, Germany, 20246
Neurochirurgische Universitätklinik des Heidelberg, Dept of Neurosurgery Recruiting
Heidelberg, Germany, 69120
Universitätsklinikum Schleswig Hollstein Lübeck (UKSH) Klinik für Neurochirugie Active, not recruiting
Lübeck, Germany, 23538
Technical University-Klinikum rechts der Isar, Abt. Neurochirurgie Active, not recruiting
München, Germany, 81675
University Regensburg, Dpt. of Neurosurgery Recruiting
Regensburg, Germany, 93053
Hungary
Debreceni Egyetem, Idegsebészet Recruiting
Debrecen, Hungary, 4032
BAZ Megyei Kórház és Egyetemi Oktató Kórház Neuroradiológiai és angiográphiás osztály Active, not recruiting
Miskolc, Hungary, 3526
Pécsi Tudományegyetem Klinikai Központ, Idegsebészeti Klinika Recruiting
Pécs, Hungary, 7623
Szegedi Tudományegyetem ÁOK Szent-Györgyi Albert Klinikai Központ, Idegsebészeti Klinika Active, not recruiting
Szeged, Hungary, 6701
Israel
Rambam Healthcare Campus, Neurology Department Not yet recruiting
Haifa, Israel, 3109601
Hadassah Medical Center Active, not recruiting
Jerusalem, Israel, 9112001
Beilinson Hospital, Rabin Medical Center, Department of Neurosurgery Active, not recruiting
Petah tikva, Israel, 4941492
The Chaim Sheba Medical Centre - Neurosurgery Active, not recruiting
Ramat Gan, Israel, 5265601
Italy
Istituto delle Scienze Neurologiche di Bologna, Dipartimento di Neurochirurgia e Neuroradiologia Interventistica Not yet recruiting
Bologna, Italy, 40139
ASST Monza, Hospital San Gerardo, TERAPIA INTENSIVA Neurochirurgica Recruiting
Monza, Italy, 20900
Azienda Ospedaliera Padova-Università degli Studi di Padova - Istituto di Anestesia e Rianimazione Active, not recruiting
Padova, Italy, 35128
Azienda Ospedaliero Universitaria di Parma, struttura complessa Neurochirurgia Not yet recruiting
Parma, Italy, 43126
Fondazione Policlinico Universitario Agostino Gemelli Università Cattolica del Sacro Cuore, UOS Terapia Intensiva Neurochirurgic Active, not recruiting
Rome, Italy, 00168
Poland
Szpital Uniwersytecki nr 1 im. dr. Antoniego Jurasza Not yet recruiting
Bydgoszcz, Poland, 85-094
Klinika Neurochirurgii Not yet recruiting
Gdańsk, Poland, 80-952
Oddział Kliniczny Neurochirurgii i Neurotraumatologii Withdrawn
Kraków, Poland, 31-501
Oddział Neurochirurgii i Neurotraumatologii z Pododdziałem Leczenia Chorób Naczyniowych Centralnego Układu Nerwowego Not yet recruiting
Poznań, Poland, 60-355
Katedra i Klinika Neurochirurgii Samodzielny Publiczny Centralny Szpital Kliniczny w Warszawie Recruiting
Warszawa, Poland, 02-097
Uniwersytecki Szpital Kliniczny nr 1 im. Norberta Barlickiego Active, not recruiting
Łódź, Poland, 90-153
Spain
Hospital Universitario Germans Trias i Pujol - Neurology Department Recruiting
Badalona, Spain, 08916
Hospital Vall d'Hebron Departamento Neuroradiología Recruiting
Barcelona, Spain, 08035
Hospital Clinic Barcelona Recruiting
Barcelona, Spain, 08036
Hospital Universitari de Bellvitge Recruiting
Barcelona, Spain, 08907
University Hospital of Gran Canaria Dr. Negrin Active, not recruiting
Las Palmas De Gran Canaria, Spain, 35010
Hospital Universitario 12 de Octubre, Departamento Neurosurgery Division Neuroradiology Active, not recruiting
Madrid, Spain, 28041
Hospital Universitari son Espasses Recruiting
Palma De Mallorca, Spain, 07014
Sweden
Sahlgrenska Universitetssjukhuset, Verksamheten för neurokirurgi, Neurosjukvården Active, not recruiting
Göteborg, Sweden, 41345
Linköping Universitetssjukhuset, Neurokirurgiska kliniken Active, not recruiting
Linköping, Sweden, 58185
Lunds Universitetssjukhus, Neurokirurgiska avd. NIVA Recruiting
Lund, Sweden, 22185
Sponsors and Collaborators
Idorsia Pharmaceuticals Ltd.
Investigators
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Study Director: Clinical Trials Idorsia Pharmaceuticals Ltd.
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Responsible Party: Idorsia Pharmaceuticals Ltd.
ClinicalTrials.gov Identifier: NCT03585270    
Other Study ID Numbers: ID-054-304
2018-000241-39 ( EudraCT Number )
First Posted: July 12, 2018    Key Record Dates
Last Update Posted: July 24, 2020
Last Verified: July 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Subarachnoid Hemorrhage
Hemorrhage
Pathologic Processes
Intracranial Hemorrhages
Cerebrovascular Disorders
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Vascular Diseases
Cardiovascular Diseases