Safety Study of Dabigatran in CADASIL

Brief Title

Safety Study of Dabigatran in CADASIL

Official Title

Phase II, Randomized, Crossover, Single Blind, Safety Trial of DABIGATRAN Versus ASA for Preventing Ischaemic Brain Lesions in Patients Affected by CADASIL

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.
    

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 Phase

Phase 2

Study Type

Interventional


Primary Outcome

Number of microbleeds on MRI

Secondary Outcome

 Major bleeding

Condition

CADASIL

Intervention

Dabigatran

Study Arms / Comparison Groups

 Dabigatran
Description:  

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Drug

Estimated Enrollment

50

Start Date

June 2011

Completion Date

February 2015

Primary Completion Date

January 2015

Eligibility 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.
      

Gender

All

Ages

18 Years - N/A

Accepts Healthy Volunteers

No

Contacts

Francesco Orzi, MD, +3933775829, [email protected]

Location Countries

Italy

Location Countries

Italy

Administrative Informations


NCT ID

NCT01361763

Organization ID

DABCAD2010



Study Sponsor

S. Andrea Hospital


Study Sponsor

Francesco Orzi, MD, Study Chair, NESMOS Department, University of Rome "La Sapienza"; St. Andrea Hospital


Verification Date

December 2013