SONICA: Safety Study of Dabigatran in CADASIL

Sponsor

S. Andrea Hospital (Other)

Overall Status

Unknown status

CT.gov ID

NCT01361763

Collaborator

(none)

Enrollment

Locations

Arms

44.1

Duration (Months)

Patients Per Site

0.6

Patients Per Site Per Month

Study Details

Study Description

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:

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.

Study Design

Study Type:

Interventional

Anticipated 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 :

Jun 1, 2011

Anticipated Primary Completion Date :

Jan 1, 2015

Anticipated Study Completion Date :

Feb 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Dabigatran	Drug: Dabigatran 110 mg twice daily
Active Comparator: Antiplatelets	Drug: Antiplatelets 100mg once a day

Arm

Intervention/Treatment

Experimental: Dabigatran

Drug: Dabigatran

110 mg twice daily

Active Comparator: Antiplatelets

Drug: Antiplatelets

100mg once a day

Outcome Measures

Primary Outcome Measures

Number of microbleeds on MRI [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

Major bleeding [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

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.