Systemic and Local Diffusion of Ethanol After Administration of Ethanol 96% Formulated in a Gel and Ethanol 98% Solution by the Percutaneous Route, in Patients With Congenital Venous Malformations:Pharmacokinetic, Pharmacodynamic and Clinical Study.
Condition: Congenital Venous Malformation
MeSH terms: Congenital Abnormalities
Intervention: Ethanol 96% Gel; Ethanol 98% Solution
Intervention MeSH terms: Ethanol
Phase: Phase 2
Study type: Interventional
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 32.0
Sex: All
Minimum age: 12 Years
Healthy volunteers: No

Summary:

      Absolute ethanol has been used "off-label" as an unmodified formulation (solution) in
      Congenital Venous Malformations (CVM). Despite its effectiveness, absolute ethanol appears
      difficult to handle because of its high diffusion capacity outside the CVM and in the blood
      circulation. A less diffusible ethanol-based product (ethanol gel) has been developed in
      order to minimize systemic and local diffusion capacities of ethanol. Therefore, the
      pharmacokinetic parameters and their clinical and paraclinical outcomes between ethanol gel
      96% and absolute ethanol need to be carried out.

      FDA Office of Orphan Products Development (FDA OOPD) : Funding source.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients of both sexes, of at least 12 years of age,

          -  For women of childbearing potential, negative pregnancy test at baseline,

          -  Patients with one clinically and radiologically (MRI) documented lesion diagnosed as
             CVM (pure or predominant),

          -  Patients for which an embolosclerotherapy by the percutaneous route is indicated as
             first line therapy of the test lesion, or for which previous treatments (i.e. surgery,
             embolosclerotherapy, laser) have been unsuccessful or insufficient,

          -  Patients with CVM lesional size of at least 12 cm3 (maximum craniocaudal dimension X
             mean dimension of 3 transverse equispaced measurements X mean dimension of 3 deepness
             equispaced measurements dimension) at MRI,

          -  Patients with focal or multifocal CVM lesion, i.e. with one or several
             well-interconnecting venous spaces and well-defined margins,

          -  Patients or parents able to follow study instructions and attend study visits,

          -  Written informed consent from the patients or parents.

        Exclusion criteria:

          -  Patients under 12 years of age,

          -  Pregnant women, nursing mothers and women of childbearing potential with no reliable
             contraception from more than 2 months,

          -  Women of childbearing potential with a positive pregnancy test at baseline,

          -  Patients with CVM of non venous predominance,

          -  Patients with CVM that are not reachable by the percutaneous route,

          -  Patients with extensive superficial skin CVM (i.e. with high risk of skin necrosis),

          -  Patients with a test lesion adjacent to major nerves (e.g. facial nerve in the parotid
             region, intramuscular regions adjacent to major nerves),

          -  Patients with facial CVM or bone involvement,

          -  Patients with small CVM lesion (<12 cm3 at MRI),

          -  Patients requiring more than 1 ml/Kg body weight (b.w.) in USA or more than 0.5 ml/Kg
             b.w. in France, or more than 30 mL of absolute ethanol to infuse,

          -  Patients with a known allergy to one of the components of the test products,

          -  Patients with a suspected allergy to iodinate.ed products,

          -  Patients with abnormal clotting parameters (platelets, partial thromboplastin,
             prothrombin time),

          -  Patients with an active inflammatory episode of the test lesion (i.e. acute or
             subacute swelling of the test lesion),

          -  Patients with complex malformations (e.g. Klippel-Trenaunay syndrome, Blue Rubber Bled
             Nevus syndrome, Muco-cutaneous familial venous malformations, Mafucci's syndrome),

          -  Patients in which a surgery, laser therapy or embolosclerotherapy of the test lesion
             has been performed within the last 12 weeks prior to study entry,

          -  Asthmatic patients who require daily medications,

          -  Patients with a non treated or non stabilized cardiac disease,

          -  Patients with a suspected right-left shunt,

          -  Patients with an intercurrent condition or a concomitant treatment which may interfere
             with a good conduct or the evaluation parameters of the study,

          -  Patients who participated in a study within the 12 weeks prior to study entry,

          -  Patients or parents who are not able or willing to follow the study instructions,

          -  Patients or parents who refuse to give written informed consent.