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Safety Study of Dabigatran in CADASIL (SONICA)

Primary Purpose

CADASIL

Status
Unknown status
Phase
Phase 2
Locations
Italy
Study Type
Interventional
Intervention
Dabigatran
Antiplatelets
Sponsored by
S. Andrea Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for CADASIL focused on measuring Dabigatran, Microbleeds, Microthrombi, CADASIL, Small Vessel Disease

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept 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.

Sites / Locations

  • Emergency Department Stroke Unit, Umberto I Hospital
  • NESMOS Department St. Andrea HospitalRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Dabigatran

Antiplatelets

Arm Description

Outcomes

Primary Outcome Measures

Number of microbleeds on MRI
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
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.

Full Information

First Posted
May 16, 2011
Last Updated
February 10, 2014
Sponsor
S. Andrea Hospital
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1. Study Identification

Unique Protocol Identification Number
NCT01361763
Brief Title
Safety Study of Dabigatran in CADASIL
Acronym
SONICA
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 Type
Interventional

2. Study Status

Record Verification Date
December 2013
Overall Recruitment Status
Unknown status
Study Start Date
June 2011 (undefined)
Primary Completion Date
January 2015 (Anticipated)
Study Completion Date
February 2015 (Anticipated)

3. Sponsor/Collaborators

Name of the Sponsor
S. Andrea Hospital

4. Oversight

Data Monitoring Committee
Yes

5. 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
CADASIL
Keywords
Dabigatran, Microbleeds, Microthrombi, CADASIL, Small Vessel Disease

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Crossover Assignment
Masking
Outcomes Assessor
Allocation
Randomized
Enrollment
50 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Dabigatran
Arm Type
Experimental
Arm Title
Antiplatelets
Arm Type
Active Comparator
Intervention Type
Drug
Intervention Name(s)
Dabigatran
Intervention Description
110 mg twice daily
Intervention Type
Drug
Intervention Name(s)
Antiplatelets
Intervention Description
100mg once a day
Primary Outcome Measure Information:
Title
Number of microbleeds on MRI
Description
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.
Time Frame
Six Months
Secondary Outcome Measure Information:
Title
Major bleeding
Description
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.
Time Frame
Six Months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Francesco Orzi, MD
Phone
+3933775829
Email
francesco.orzi@uniroma1.it
First Name & Middle Initial & Last Name or Official Title & Degree
Giulio Caselli, MD
Phone
3478654946
Email
giulio.caselli@gmail.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Francesco Orzi, MD
Organizational Affiliation
NESMOS Department, University of Rome "La Sapienza"; St. Andrea Hospital
Official's Role
Study Chair
Facility Information:
Facility Name
Emergency Department Stroke Unit, Umberto I Hospital
City
Rome
ZIP/Postal Code
00161
Country
Italy
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Danilo Toni, MD
Phone
+39-06-49979595
Email
danilo.toni@uniroma1.it
First Name & Middle Initial & Last Name & Degree
Agata Correnti, MD
First Name & Middle Initial & Last Name & Degree
Emanuele Puca, MD
Facility Name
NESMOS Department St. Andrea Hospital
City
Rome
ZIP/Postal Code
00189
Country
Italy
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Francesco Orzi, MD
Phone
+39-06-33775829
Email
francesco.orzi@uniroma1.it
First Name & Middle Initial & Last Name & Degree
Giulio Caselli, MD
Phone
+39-347-8654946
Email
giulio.caselli@gmail.com
First Name & Middle Initial & Last Name & Degree
Giulio Caselli, MD
First Name & Middle Initial & Last Name & Degree
Barbara Casolla, MD

12. IPD Sharing Statement

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Safety Study of Dabigatran in CADASIL

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