Ignite Creation Date:
2024-05-06 @ 7:16 AM
Last Modification Date:
2024-10-26 @ 11:47 AM
Study NCT ID:
NCT02509468
Status:
COMPLETED
Last Update Posted:
2019-09-18
First Post:
2015-07-15
Brief Title:
suPERficial Slow-flow Vascular malFORMations Treated With sirolimUS
Sponsor:
University Hospital Tours
Organization:
University Hospital Tours
Study Overview
Official Title:
Treatment of Superficial Voluminous Complicated Slow-flow Vascular Malformations With Sirolimus a Phase 2 Trial in Children Observational-phase Designed
Status:
COMPLETED
Status Verified Date:
2019-09
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
PERFORMUS
Brief Summary:
The most recent classification adopted by International Society for the Study of Vascular Anomalies ISSVA in 1996 and updated in Melbourne in 2014 divides these lesions into two broad categories vascular tumors and vascular malformations Vascular malformations VMs are subdivided into high-flow VM and slow-flow VM
Slow-flow VMs consist of congenital anomalies which may involve abnormal capillaries vessels venous vessels lymphatic vessels or combination of several of them They can be superficial involving cutaneous and subcutaneous tissues andor may have visceral involvement They can be limited or diffuse and are sometimes components of genetic hypertrophic syndromes
The diagnosis of slow-flow VMs is performed on physical examination biopsy may be required for confirmation and is completed with imaging ultrasonography and magnetic resonance imaging MRI Slow-flow VMs may be particularly voluminous associated with underlying hypertrophy responsible for functional impairment painful associated with seepage or continuous cutaneous bleeding complicated with visceral signs or hematologic disturbances anemia thrombopenia Management requires dedicated multispecialty care There are no guidelines for treatment and management may include no intervention - but natural history of these VMs is progressive worsening - compression by physical bandage sclerotherapy resection when feasibleanti-inflammatory or anti-coagulation drugs
Case reports and series have provided evidence for supporting the need for a clinical trial of sirolimus by reporting successful treatment on several children with complicated vascular anomalies The choice of sirolimus is rational Mammalian target of rapamycin mTOR is a serinethreonine kinase regulated by phosphoinositide-3-kinase involved in cell mobility cell growth and angiogenesis Sirolimus inhibits mTOR which induces inhibition of angiogenesis in particular lymphangiogenesis which has been demonstrated in several models
Slow-flow VMs consist of congenital anomalies which may involve abnormal capillaries vessels venous vessels lymphatic vessels or combination of several of them They can be superficial involving cutaneous and subcutaneous tissues andor may have visceral involvement They can be limited or diffuse and are sometimes components of genetic hypertrophic syndromes
The diagnosis of slow-flow VMs is performed on physical examination biopsy may be required for confirmation and is completed with imaging ultrasonography and magnetic resonance imaging MRI Slow-flow VMs may be particularly voluminous associated with underlying hypertrophy responsible for functional impairment painful associated with seepage or continuous cutaneous bleeding complicated with visceral signs or hematologic disturbances anemia thrombopenia Management requires dedicated multispecialty care There are no guidelines for treatment and management may include no intervention - but natural history of these VMs is progressive worsening - compression by physical bandage sclerotherapy resection when feasibleanti-inflammatory or anti-coagulation drugs
Case reports and series have provided evidence for supporting the need for a clinical trial of sirolimus by reporting successful treatment on several children with complicated vascular anomalies The choice of sirolimus is rational Mammalian target of rapamycin mTOR is a serinethreonine kinase regulated by phosphoinositide-3-kinase involved in cell mobility cell growth and angiogenesis Sirolimus inhibits mTOR which induces inhibition of angiogenesis in particular lymphangiogenesis which has been demonstrated in several models
Detailed Description:
Vascular anomalies include a heterogeneous group of disorders of newborns and children While infantile hemangioma are common 10 of infants generally not complicated and easily managed the majority of other vascular anomalies are rare 2 altogether and have no guidelines for management The most recent classification adopted by International Society for the Study of Vascular Anomalies ISSVA in 1996 divides these lesions into two broad categories vascular tumors and vascular malformations Vascular malformations VMs are subdivided into high-flow VM and slow-flow VM
Slow-flow VMs consist of congenital anomalies which may involve abnormal capillaries vessels venous vessels lymphatic vessels or combination of several of them They can be superficial involving cutaneous and subcutaneous tissues andor may have visceral involvement They can be limited or diffuse and are sometimes components of genetic hypertrophic syndromes They always result from defective embryologic vasculogenesis
The diagnosis of slow-flow VMs is performed on physical examination - a biopsy may be required for confirmation - and is completed with imaging which includes ultrasonography and magnetic resonance imaging MRI Slow-flow VMs may be simple to manage or can be complicated for several reasons they may be particularly voluminous associated with underlying hypertrophy responsible for functional impairment painful associated with seepage or continuous cutaneous bleeding complicated with visceral signs or hematologic disturbances anemia thrombopenia Management requires dedicated multispecialty care There are no guidelines for treatment and management may include no intervention - but natural history of these VMs is progressive worsening - compression by physical bandage sclerotherapy resection when feasible anti-inflammatory or anti-coagulation drugs
The vast majority of literature reporting medical therapies consists of paediatric case reports and is complicated by publication bias inconsistent use of nomenclature and absence of clinical trials Case reports and series have provided evidence for supporting the need for a clinical trial of sirolimus by reporting successful treatment on several children with complicated vascular anomalies The choice of sirolimus is rational Mammalian target of rapamycin mTOR is a serinethreonine kinase regulated by phosphoinositide-3-kinase involved in cell mobility cell growth and angiogenesis Sirolimus inhibits mTOR which induces inhibition of angiogenesis in particular lymphangiogenesis which has been demonstrated in several models
Randomized observational-phase design Feldman et al J Clin Epidemiol 200154550-557
each patient will be followed during a 12-month-period
each patient will start by an observational period and will end being treated by sirolimus
at a random date between month 4 and month 8 each patient will switch from the observational period to the sirolimus period Therefore each patient will be hisher own control as in a cross-over trial but the difference is that the cross-over is all in one direction from observational period to treatment period This explains why variation in volume will be standardized by period durations
As specified by Feldman et al the randomized placebo-phase design is well adapted in situations where a placebo controlled study would be perceived as being unacceptable by enrolling physicians and by patient and may be especially useful when highly potent therapies for rare diseases
Slow-flow VMs consist of congenital anomalies which may involve abnormal capillaries vessels venous vessels lymphatic vessels or combination of several of them They can be superficial involving cutaneous and subcutaneous tissues andor may have visceral involvement They can be limited or diffuse and are sometimes components of genetic hypertrophic syndromes They always result from defective embryologic vasculogenesis
The diagnosis of slow-flow VMs is performed on physical examination - a biopsy may be required for confirmation - and is completed with imaging which includes ultrasonography and magnetic resonance imaging MRI Slow-flow VMs may be simple to manage or can be complicated for several reasons they may be particularly voluminous associated with underlying hypertrophy responsible for functional impairment painful associated with seepage or continuous cutaneous bleeding complicated with visceral signs or hematologic disturbances anemia thrombopenia Management requires dedicated multispecialty care There are no guidelines for treatment and management may include no intervention - but natural history of these VMs is progressive worsening - compression by physical bandage sclerotherapy resection when feasible anti-inflammatory or anti-coagulation drugs
The vast majority of literature reporting medical therapies consists of paediatric case reports and is complicated by publication bias inconsistent use of nomenclature and absence of clinical trials Case reports and series have provided evidence for supporting the need for a clinical trial of sirolimus by reporting successful treatment on several children with complicated vascular anomalies The choice of sirolimus is rational Mammalian target of rapamycin mTOR is a serinethreonine kinase regulated by phosphoinositide-3-kinase involved in cell mobility cell growth and angiogenesis Sirolimus inhibits mTOR which induces inhibition of angiogenesis in particular lymphangiogenesis which has been demonstrated in several models
Randomized observational-phase design Feldman et al J Clin Epidemiol 200154550-557
each patient will be followed during a 12-month-period
each patient will start by an observational period and will end being treated by sirolimus
at a random date between month 4 and month 8 each patient will switch from the observational period to the sirolimus period Therefore each patient will be hisher own control as in a cross-over trial but the difference is that the cross-over is all in one direction from observational period to treatment period This explains why variation in volume will be standardized by period durations
As specified by Feldman et al the randomized placebo-phase design is well adapted in situations where a placebo controlled study would be perceived as being unacceptable by enrolling physicians and by patient and may be especially useful when highly potent therapies for rare diseases
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 2015-001096-43 | EUDRACT_NUMBER | None | None |