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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.

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Orfagen
ClinicalTrials.gov Identifier:
NCT00462462
First received: April 16, 2007
Last updated: November 6, 2014
Last verified: November 2014
  Purpose

Absolute ethanol has been used "off-label" as an unmodified formulation (solution) in 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 OOPD: Funding source.


Condition Intervention Phase
Congenital Venous Malformation
Drug: Ethanol 96% Gel
Drug: Ethanol 98% Solution
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
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.

Further study details as provided by Orfagen:

Primary Outcome Measures:
  • To compare the systemic exposure to ethanol with the two test products. [ Time Frame: study end ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • To compare the systemic (cardiopulmonary, hematological, metabolic) and local outcome of the two test products. [ Time Frame: Study end ] [ Designated as safety issue: Yes ]
  • To compare the embolosclerosing activity of L0122 gel and absolute ethanol on size reduction of CVM. [ Time Frame: study end ] [ Designated as safety issue: No ]
  • To compare the clinical efficacy (patient benefit) of the two test products. [ Time Frame: study end ] [ Designated as safety issue: No ]

Enrollment: 32
Study Start Date: May 2007
Study Completion Date: June 2010
Primary Completion Date: June 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
Ethanol gel
Drug: Ethanol 96% Gel
Active Comparator: 2
Ethanol solution
Drug: Ethanol 98% Solution

  Eligibility

Ages Eligible for Study:   12 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00462462

Locations
United States, Maryland
Johns Hopkins Medical Institutions
Baltimore, Maryland, United States, 21287
France
Hôpital Bretonneau Service de neuroradiologie
Tours Cedex 1, France, 37044
Sponsors and Collaborators
Orfagen
Investigators
Study Director: PATRICK DUPUY, MD ORFAGEN LABORATORIES (France)
Principal Investigator: SALLY E MITCHELL, MD Johns Hopkins Medical Institution (Baltimore, USA)
Principal Investigator: Denis HERBRETEAU, MD Hôpital Bretonneau (Tours, France)
  More Information

No publications provided

Responsible Party: Orfagen
ClinicalTrials.gov Identifier: NCT00462462     History of Changes
Other Study ID Numbers: L00122 GI 201 (ORF)
Study First Received: April 16, 2007
Last Updated: November 6, 2014
Health Authority: United States: Food and Drug Administration
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

Additional relevant MeSH terms:
Congenital Abnormalities
Ethanol
Pharmaceutical Solutions
Anti-Infective Agents
Anti-Infective Agents, Local
Central Nervous System Agents
Central Nervous System Depressants
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on November 25, 2014