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Safety Study of Dabigatran in CADASIL (SONICA)

The recruitment status of this study is unknown because the information has not been verified recently.
Verified May 2011 by S. Andrea Hospital.
Recruitment status was  Recruiting
Sponsor:
Information provided by:
S. Andrea Hospital
ClinicalTrials.gov Identifier:
NCT01361763
First received: May 16, 2011
Last updated: July 1, 2011
Last verified: May 2011
History of Changes
  Purpose

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 Intervention Phase
CADASIL
 Drug: Dabigatran
Drug: Antiplatelets
 Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Crossover Assignment
Masking: Single Blind (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

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by S. Andrea Hospital:

Primary Outcome Measures:
  • Number of microbleeds on MRI [ Time Frame: Six Months ] [ Designated as safety issue: Yes ]
    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:
  • Major bleeding [ Time Frame: Six Months ] [ Designated as safety issue: Yes ]
    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.


Estimated Enrollment: 50
Study Start Date: June 2011
Estimated Study Completion Date: April 2012
Estimated Primary Completion Date: January 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Dabigatran Drug: Dabigatran
110 mg twice daily
Active Comparator: Antiplatelets Drug: Antiplatelets
100mg once a day

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
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
Please refer to this study by its ClinicalTrials.gov identifier: NCT01361763

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

Locations
Italy
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            
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            
Sponsors and Collaborators
S. Andrea Hospital
Investigators
Study Chair: Francesco Orzi, MD NESMOS Department, University of Rome "La Sapienza"; St. Andrea Hospital
  More Information

Additional Information:
Center for experimental neurological therapies.  This link exits the ClinicalTrials.gov site

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
Study First Received: May 16, 2011
Last Updated: July 1, 2011
Health Authority: Italy: Ministry of Health

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

Additional relevant MeSH terms:
CADASIL
Dementia, Multi-Infarct
Dementia, Vascular
Cerebrovascular Disorders
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Cerebral Arterial Diseases
Intracranial Arterial Diseases
Dementia
 Vascular Diseases
Cardiovascular Diseases
Genetic Diseases, Inborn
Cerebral Infarction
Brain Infarction
Brain Ischemia
Stroke
Delirium, Dementia, Amnestic, Cognitive Disorders
Mental Disorders

ClinicalTrials.gov processed this record on May 23, 2013