Clinical trial NCT00462462: 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.
Official title: 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.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Congenital Venous Malformation
Lead sponsor: Orfagen
Sponsor class: INDUSTRY
Collaborators: name: FDA Office of Orphan Products Development
First posted: 2007-04-19
Enrollment: 32
Sex: ALL
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL

Brief 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.

Primary outcomes:
measure: Systemic Exposure to Ethanol With the Two Test Products: Determination of the Maximum Plasma Concentration (Cmax)
timeFrame: Baseline visit (just before and during test product infusion procedure)
Secondary outcomes:
measure: Systemic (Cardiopulmonary, Hematological, Metabolic) and Local Outcome of the Two Test Products.
timeFrame: Study end
measure: Change in Volume of Congenital Venous Malformation (CVM) From Screening to Study End (Day 112 Visit).
timeFrame: Screening and study end (Day 112)
measure: Patient Benefit
timeFrame: study end
Other outcomes:
Locations:
city: Baltimore
country: United States
facility: Johns Hopkins Medical Institutions
state: Maryland
city: Tours Cedex 1
country: France
facility: Hôpital Bretonneau Service de neuroradiologie
Study officials:
affiliation: ORFAGEN LABORATORIES (France)
name: PATRICK DUPUY, MD
role: STUDY_DIRECTOR
affiliation: Johns Hopkins Medical Institution (Baltimore, USA)
name: SALLY E MITCHELL, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Hôpital Bretonneau (Tours, France)
name: Denis HERBRETEAU, MD
role: PRINCIPAL_INVESTIGATOR
References: