|E.1 Medical condition or disease under investigation
|Medical condition(s) being investigated
|Medical condition in easily understood language
|vascular abnormality of the venous system
|Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16]
|E.1.2 Medical condition or disease under investigation
|Venous malformation NOS
|System Organ Class
|10010331 - Congenital, familial and genetic disorders
|Condition being studied is a rare disease
|E.2 Objective of the trial
|Main objective of the trial
|Compare the efficacy and side effects of bleomycin and sodium tetradecyl sulfate (Fibrovein ™) in the treatment of venous malformations. Group differences in reported pain after treatment will be the main effect variable.
|Secondary objectives of the trial
|Secondary outcome measures are relaps rate, physical function, emotional function, subjective assessment of improvement and additional symptoms or side effects.
|Trial contains a sub-study
|Full title, date and version of each sub-study and their related objectives
|1. Measure the proportion of patients with a risk of nerve involvement caused by a nearby venous malformation by having the patient undergo a thorough diagnostic imaging (ultrasound and magnetic resonance), clinical neurological examination, thermal testing, and EMG nevrografi in advance of any treatment. Group Differences in the incidence of neuropathic pain is the main variable.
2. Quality of life survey of patients with venous and arteriovenous malformations using SF-36 questionnaire. The purpose of this study will be:
A. Examining health-related quality of life in patients with vascular malformations before treatment of the condition.
B. Examining health-related quality of life in patients with vascular malformations 1 year after stopping treatment or completed the diagnosis, unless the treatment is implemented.
3. MRI(magnetic resonance imaging) examination of patients with venous and arteriovenous malformations using 2 additional sequences named TWIST (time-resolved angiography with interleaved stochastic trajectories) and VIBE (volume-interpolated breath-hold examination). The purpose of this study will be:
A. Examining the usefulness of MRI sequences TWIST and VIBE in the study of venous and arteriovenous malformations.
B. Compare TWIST MRA with conventional angiography (gold standard), for the representation of distribution and description of flow dynamics in arteriovenous malformations.
C. Examine whether haemodynamics in vascular malformations presented with TWIST and VIBE MRI can predict the treatment effect and clinical outcome.
|Principal inclusion criteria
|All patients of both sexes over 12 years referred to hospital with suspected venous malformation will be requested study participation. Written consent must be provided. Patients between 12 and 16 must have parental consent.
|Principal exclusion criteria
|Contraindications to the use of bleomycin:
compromised lung function
Previously demonstrated hypersensitivity to bleomycin.
Known previous malignant disease
Contraindications to the use of fibrovein:
Allergy to sodium tetradecyl sulfate
Heart Failure / Pulmonary Edema
o Previously, severe reaction to X-ray contrast agent
o severe allergies and / or severe bronchial asthma
o Local or systemic infection
o Severe illness that complicates monitoring
o Pregnant / planning pregnancy or breast-feeding
|E.5 End points
|Primary end point(s)
|Primary endpoint is reduction in pain scores one year after treatment with at least 30% difference between the most compared with the least efficacous treatment.
VAS (Visual Analogue Scale)shall be used and the standard deviation is estimated to be 2.8 .
|Timepoint(s) of evaluation of this end point
| The primary end point is status after one year.
|Secondary end point(s)
|Changes in pain intensity as a function of time and treatment allocation at every time point.
|Timepoint(s) of evaluation of this end point
|By using various questionnaires that pasients have to fill out, the pain will be measured before starting treatment and then 6 weeks and 12 months after ended treatment.
|E.6 and E.7 Scope of the trial
|Scope of the trial
|Trial type and phase
|Human pharmacology (Phase I)
|First administration to humans
|Other trial type description
|Therapeutic exploratory (Phase II)
|Therapeutic confirmatory (Phase III)
|Therapeutic use (Phase IV)
|E.8 Design of the trial
| Comparator of controlled trial
|Other medicinal product(s)
|Number of treatment arms in the trial
The trial involves single site in the Member State concerned
| The trial involves multiple sites in the Member State concerned
|The trial involves multiple Member States
|E.8.6 Trial involving sites outside the EEA
|Trial being conducted both within and outside the EEA
|Trial being conducted completely outside of the EEA
|Trial has a data monitoring committee
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|E.8.9 Initial estimate of the duration of the trial
|In the Member State concerned years
|In the Member State concerned months
|In the Member State concerned days