Safety Study of Dabigatran in CADASIL (SONICA)
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.
|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|
- 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.
- 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.
|Study Start Date:||June 2011|
|Estimated Study Completion Date:||February 2015|
|Estimated Primary Completion Date:||January 2015 (Final data collection date for primary outcome measure)|
110 mg twice daily
|Active Comparator: Antiplatelets||
100mg once a day
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:
- 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;
- 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.
|Contact: Francesco Orzi, MDfirstname.lastname@example.org|
|Contact: Giulio Caselli, MDemail@example.com|
|NESMOS Department St. Andrea Hospital||Recruiting|
|Rome, Italy, 00189|
|Contact: Francesco Orzi, MD +39-06-33775829 firstname.lastname@example.org|
|Contact: Giulio Caselli, MD +39-347-8654946 email@example.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 firstname.lastname@example.org|
|Contact: Agata Correnti, MD|
|Principal Investigator: Emanuele Puca, MD|
|Study Chair:||Francesco Orzi, MD||NESMOS Department, University of Rome "La Sapienza"; St. Andrea Hospital|