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Safety Study of Dabigatran in CADASIL (SONICA)

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ClinicalTrials.gov Identifier: NCT01361763
Recruitment Status : Unknown
Verified December 2013 by S. Andrea Hospital.
Recruitment status was:  Recruiting
First Posted : May 27, 2011
Last Update Posted : February 11, 2014
Sponsor:
Information provided by:
S. Andrea Hospital

Study Description
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Brief Summary:
This study is a Phase II, randomized, crossover trial designed to compare one fixed dose of dabigatran with open-label use of ASA in patients affected by CADASIL; the study is a safety trial, and the primary objective is to assess that dabigatran is not less safe than ASA in subjects with CADASIL.

Condition or disease Intervention/treatment Phase
CADASIL Drug: Dabigatran Drug: Antiplatelets Phase 2

Detailed Description:

The primary endpoint is the number of microbleeds, as measured by MRI, at 90 days of follow up.

The study is based on the hypothesis that drugs inhibitor of the thrombin is more effective than ASA in preventing vessel obstruction. The rationale behind the study is based on the assumption that: a) the formation of microthrombi is relevant to the clinical expression of the CADASIL disease, and b) thrombin inhibitors are more effective than antiplatelet drugs in preventing lesions by microvessel obstruction.

Eligible patients will be randomized into one of the 2 treatment groups:

  1. One week wash-out (W1), Dabigatran one tablet 100mg twice a day for 12 weeks, a second one week wash-out (W2), treatment with ASA one tablet of 100mg/day once a day for 12 weeks;
  2. The same scheme repeated with reversed sequence No initial wash-out week will be required for patients in group 2 already treated with ASA.

Clinical and instrumental evaluations will be carried out during the first (W1) and second wash-out weeks (W2), and at the end of the study (during the week that follows the second treatment regimen (W3). Each evaluation will consist of physical examination, blood tests and MRI.

Safety is evaluated on the basis of brain microbleeds and severe haemorrhages.


Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 50 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Single (Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Phase II, Randomized, Crossover, Single Blind, Safety Trial of DABIGATRAN Versus ASA for Preventing Ischaemic Brain Lesions in Patients Affected by CADASIL
Study Start Date : June 2011
Estimated Primary Completion Date : January 2015
Estimated Study Completion Date : February 2015

Resource links provided by the National Library of Medicine

U.S. FDA Resources

Arms and Interventions
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Arm Intervention/treatment
Experimental: Dabigatran Drug: Dabigatran
110 mg twice daily
Active Comparator: Antiplatelets Drug: Antiplatelets
100mg once a day


Outcome Measures
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Primary Outcome Measures :
  1. Number of microbleeds on MRI [ Time Frame: Six Months ]
    Primary endpoint is defined as the difference in number of microbleeds on MRI images taken at the end of the 2 treatments (i.e, during W2 and W3). Secondary endpoint is major bleeding. The neuroradiologists (or trained neurologists) who will examine the images on MRI will be blind to treatment.


Secondary Outcome Measures :
  1. Major bleeding [ Time Frame: Six Months ]
    Severe haemorrhages are defined as a reduction of the haemoglobin level by at least 20g per litre, need of a transfusion of at least 2 units of blood, or symptomatic bleeding of an organ or critical area. Life threatening haemorrhages are a subcategory of severe hemorrhages defined as: fatal haemorrhages, symptomatic intracranial haemorrhages, haemorrhages with a diminution of haemoglobin level of at least 50g per litre or that require transfusion of at least 4 blood units, or surgery. All the other haemorrhages are considered minor.


Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients aged 18 years or older diagnosed with CADASIL according genetic test will be eligible.

Exclusion Criteria:

  • Treatment with antiplatelet drugs for a condition different from CADASIL;
  • conditions associated with an increased risk of bleeding (major surgery within the previous month, planned surgery or intervention within the next 3 months;
  • history of intracranial, intraocular, spinal, retroperitoneal or atraumatic intra‐articular bleeding;
  • gastrointestinal hemorrhage within the past year;
  • symptomatic or endoscopically documented gastroduodenal ulcer disease in the previous 30 days; hemorrhagic disorder or bleeding diathesis;
  • need for anticoagulant treatment of disorders other than atrial fibrillation; fibrinolytic agents within 48 hours of study entry; uncontrolled hypertension (systolic blood pressure greater than 180 mm Hg and/or diastolic blood pressure greater than 100 mm Hg);
  • recent malignancy or radiation therapy (within 6 months) and not expected to survive 3 years; severe renal impairment (estimated creatinine clearance 30 mL/min or less);
  • active infective endocarditis;
  • active liver disease (including but not limited to persistent ALT, AST, Alk Phos greater than twice the upper limit of the normal range; active hepatitis C (positive HCV RNA);
  • active hepatitis B (HBs antigen +, anti HBc IgM +), active hepatitis A);
  • women who are pregnant or of childbearing potential who refuse to use a medically acceptable form of contraception throughout the study.
Contacts and Locations
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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): NCT01361763


Contacts
Contact: Francesco Orzi, MD +3933775829 francesco.orzi@uniroma1.it
Contact: Giulio Caselli, MD 3478654946 giulio.caselli@gmail.com

Locations
Italy
Emergency Department Stroke Unit, Umberto I Hospital Not yet recruiting
Rome, Italy, 00161
Contact: Danilo Toni, MD    +39-06-49979595    danilo.toni@uniroma1.it   
Contact: Agata Correnti, MD         
Principal Investigator: Emanuele Puca, MD         
NESMOS Department St. Andrea Hospital Recruiting
Rome, Italy, 00189
Contact: Francesco Orzi, MD    +39-06-33775829    francesco.orzi@uniroma1.it   
Contact: Giulio Caselli, MD    +39-347-8654946    giulio.caselli@gmail.com   
Principal Investigator: Giulio Caselli, MD         
Principal Investigator: Barbara Casolla, MD         
Sponsors and Collaborators
S. Andrea Hospital
Investigators
Study Chair: Francesco Orzi, MD NESMOS Department, University of Rome "La Sapienza"; St. Andrea Hospital
More Information
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Publications:

Responsible Party: Francesco Orzi, Department of Neuroscience, Mental Healt and Sensory Organs (NESMOS); University of Rome "La Sapienza"
ClinicalTrials.gov Identifier: NCT01361763     History of Changes
Other Study ID Numbers: DABCAD2010
First Posted: May 27, 2011    Key Record Dates
Last Update Posted: February 11, 2014
Last Verified: December 2013

Keywords provided by S. Andrea Hospital:
Dabigatran
Microbleeds
Microthrombi
CADASIL
Small Vessel Disease

Additional relevant MeSH terms:
CADASIL
Dementia, Multi-Infarct
Cerebral Small Vessel Diseases
Cerebrovascular Disorders
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Dementia, Vascular
Cerebral Arterial Diseases
Intracranial Arterial Diseases
Dementia
Vascular Diseases
Cardiovascular Diseases
Genetic Diseases, Inborn
 Cerebral Infarction
Brain Infarction
Brain Ischemia
Stroke
Neurocognitive Disorders
Mental Disorders
Dabigatran
Antithrombins
Serine Proteinase Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anticoagulants