Vascular AnomalyNCT03583307
Efficacy and Safety of Sirolimus to Vascular Anomalies
A study testing Sirolimus in people with Vascular Anomaly, run by West China Hospital at 1 site in China.
Trial summary
To evaluate the safety and efficacy of Sirolimus in complicated vascular anomalies in Chinese children Read more about this study
- Who is it for?
- Ages 0 to 18 years
- Conditions the study is for
- Vascular Anomaly
- What is being tested?
- Sirolimus
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 126 participants
- Where
- 1 siteChina
- Study dates
- 1 Jun 2018to 19 Feb 2021
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 0 to 18 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- All patients included in the present research must be diagnosed with one of the following vascular anomalies:
- Kaposiform Hemangioendotheliomas without Kasabach-Merritt Phenomenon
- Tufted Angioma without Kasabach-Merritt Phenomenon
- Capillary Malformations
- Lymphatic Malformations
- Venous Malformations
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- Capillary-Venous Malformation (CVM)
- Capillary-Lymphatic Malformation (CLM)
- Lymphatic-Venous Malformation (LVM)
- Capillary-Lymphatic-Venous Malformation (CLVM)
- Multifocal Lymphangiomatosis and Thrombocytopenia (MLT)
- Patients must be 0 - 18 years of age at the time of study entry.
- Without functional impairment requiring treatment of corticosteroid.
- Organ function requirements:
- Adequate liver function Total bilirubin less than or equal to 1.5 x upper limit of normal (ULN)for age, and alanine transaminase (ALT) and aspartate aminotransferase (AST) less than or equal to 2.5 x upper limit normal (ULN) for age.
- Adequate renal function 0-5 years of age maximum serum creatinine (mg/dL) of 0.8 6-10 years of age maximum serum creatinine (mg/dL) of 1.0 11-15 years of age maximum serum creatinine (mg/dL) of 1.2 16-18 years of age maximum serum creatinine (mg/dL) of 1.5
- Adequate bone marrow function:
- Absolute Neutrophil Count (ANC) greater than or equal to 1 x 10 to the ninth/Liter
- Consent of parents (or the person having parental authority in families): Signed and dated written informed consent.
Who cannot join
- Allergy to sirolimus or other rapamycin analogues.
- Allergy to sirolimus or other rapamycin analogues.
- Any known evidence of significant local or systemic uncontrolled infection, defined as receiving intravenous antibiotics at the time of randomization.
- Patients must not be known to be Human Immunodeficiency Virus positive or known immunodeficiency. Testing is not required unless a condition is suspected.
- Other concurrent severe and/or uncontrolled medical disease which could compromise participation in the study (e.g. uncontrolled diabetes, uncontrolled hypertension, severe malnutrition, chronic liver or renal disease, active upper gastrointestinal tract ulceration).
- Impairment of gastrointestinal function or chronic gastrointestinal disease that may significantly alter the absorption of sirolimus.
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- Patients who have a history of malignancy.
- Patients with an inability to participate or to follow the study treatment and assessment plan.
- Patients who have a history of treatment with sirolimus or other mTOR inhibitor.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Efficacy and Safety of Sirolimus in the Treatment of the Complicated Vascular Anomalies
To evaluate the safety and efficacy of Sirolimus in complicated vascular anomalies in Chinese children
Read the detailed description
Vascular anomalies are composed of vascular tumors and vascular malformations. The prognosis of vascular anomalies is significantly variable. Most of them had a benign course. However, complicated vascular anomalies can lead to disfigurement, organ disfunction and life-threatening with significant morbidity and mortality. Traditional treatments, including steroids, vincristine, cyclophosphamide and surgery, had limited response to complicated vascular anomalies. In the past few years, the inhibitor of the mammalian target of rapamycin (mTOR) signaling pathway-sirolimus has emerged as a treatment for severe vascular anomalies. Besides, preclinical studies also showed that the Phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt)/mTOR pathway play an important role in the development of vascular tumors and vascular malformations. However, the exact efficacious rate and complications of sirolimus are still unknow in china because of the lack of large scale of prospective studies. Therefore, it's important to perform this prospective study to determine the safety and efficacy of sirolimus in the treatment of Chinese children with complicated vascular anomalies, and this study will also make contributions to the diagnoses and treatments of vascular anomalies.
- Conditions
- Vascular Anomaly
- Being tested
- Sirolimus
- Keywords
- Sirolimus, Vascular anomalies
- Medical subject headings
- Vascular Malformations
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SirolimusDrug
Also called Rapamycin
Sirolimus was initiated at a dosage of 0.8 mg/m2 administered twice daily. Subsequently, the sirolimus dosage was adjusted monthly to achieve trough levels between 10 and 15 ng/mL.
| Study group | Role | What they receive |
|---|---|---|
| Sirolimus | Experimental | Not described Receives: Drug: Sirolimus |
What is being measured
The primary outcome is the main question the study is designed to answer.
Volumetric changes in complicated vascular anomalies to sirolimus
Response to sirolimus treatment was measured by volumetric magnetic resonance imaging (MRI) analyses, which were performed at baseline and 6 and 12 months after treatment and were independently assessed by 2 radiologists. Changes in size of vascular anomalies were classified as further growth (increase of ≥10%), no change (<10% increase and <10% decrease), partial involution (decrease of ≥10% and <75%), nearly complete involution (decrease of ≥75% and <100%), or complete involution (100%).
Photographs of the complicated vascular anomalies were taken at months 0, 3, 6 and 12 by a medical photographer.
Complete/nearly complete resolution of the vascular anomalies at month 12 compared to baseline based on the intra-patient blinded centralized independent qualitative assessments of month 12 MRI.
Measured: Baseline, 6, and 12 months
The changes in the patient's symptoms and/or complications.
Measured: Baseline, 3, 6, and 12 months
Secondary outcomes (4)
Quality of Life in patients by the Pediatric Quality of Life Inventory TM (PedsQLTM) 4.0 Generic Core Scales.
The PedsQL 4.0 Generic Core Scales encompass: 1) Physical Functioning (8 items), 2) Emotional Functioning (5 items), 3) Social Functioning (5 items), and 4) School Functioning (5 items), and were developed through focus groups and cognitive interviews. The PedsQL 4.0 Generic Core Scales are comprised of parallel child self-report (ages 5-18) and parent proxy-report formats (ages 0-18). A 5-point response scale is utilized across child self-report for ages 8 to 18 and parent proxy-report (0=never a problem; 1=almost never a problem; 2=sometimes a problem; 3=often a problem; 4=almost always a problem). For patients between ages 5-7, the response scale is simplified to a 3-point scale (0=not at all a problem; 2=sometimes a problem; 4=a lot of a problem. Items are reverse-scored and linearly transformed to a 0 to 100 scale (0=100, 1=75, 2 =50, 3=25, 4=0). Scale Scores are computed as the sum of the items divided by the number of items answered.
Measured: Baseline, 6, 12 months
Measuring the impact of vascular anomalies on family functioning by PedsQLTM 4.0 Family Impact Module (FIM).
Measured: Baseline, 6, 12 months
Frequency of adverse events as assessed by CTCAE v4.0
Measured: Baseline, 3, 6, 12 months
Changes in plasma levels fibrinogen and/ or D-dimers
Measured: Baseline, 3, 6, 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Jul 2018
- Study start1 Jun 2018
- Primary completion19 Feb 2021
- Study completion19 Feb 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Vascular AnomalyStudies of the same condition, open and under way.
- More trials run by West China HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 126 participants (actual)
Sponsor and investigators
- Lead sponsor
- West China Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Yi Ji, West China Hospital
- Investigators
- Yi Ji, Principal investigator, West China Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03583307
- Sponsor's protocol ID
- 2018-618
- Status last verified
- Mar 2022
- First submitted
- 17 Jun 2018
- Last updated
- 15 Mar 2022
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Ji Y, Chen S, Yang K, Zhou J, Zhang X, Jiang X, Xu X, Lu G, Qiu L, Kong F, Zhang Y. A prospective multicenter study of sirolimus for complicated vascular anomalies. J Vasc Surg. 2021 Nov;74(5):1673-1681.e3. doi: 10.1016/j.jvs.2021.04.071. Epub 2021 May 31.
PubMed 34082006
Study at a glance
From the registry record, last updated by the sponsor on 15 Mar 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Efficacy and Safety of Sirolimus in the Treatment of the Complicated Vascular Anomalies
- ClinicalTrials.gov ID
- NCT03583307
- Acronym / sponsor ID
- 2018-618
- Conditions
- Vascular Anomaly
- Keywords
- Sirolimus, Vascular anomalies
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 126 participants (actual)
- Lead sponsor
- West China HospitalUniversity, hospital or other
- Study start
- 1 Jun 2018 (actual)
- Primary completion
- 19 Feb 2021 (actual)
- Study completion
- 19 Feb 2021 (actual)
- First posted
- 11 Jul 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
To evaluate the safety and efficacy of Sirolimus in complicated vascular anomalies in Chinese children
Detailed description
Vascular anomalies are composed of vascular tumors and vascular malformations. The prognosis of vascular anomalies is significantly variable. Most of them had a benign course. However, complicated vascular anomalies can lead to disfigurement, organ disfunction and life-threatening with significant morbidity and mortality. Traditional treatments, including steroids, vincristine, cyclophosphamide and surgery, had limited response to complicated vascular anomalies. In the past few years, the inhibitor of the mammalian target of rapamycin (mTOR) signaling pathway-sirolimus has emerged as a treatment for severe vascular anomalies. Besides, preclinical studies also showed that the Phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt)/mTOR pathway play an important role in the development of vascular tumors and vascular malformations. However, the exact efficacious rate and complications of sirolimus are still unknow in china because of the lack of large scale of prospective studies. Therefore, it's important to perform this prospective study to determine the safety and efficacy of sirolimus in the treatment of Chinese children with complicated vascular anomalies, and this study will also make contributions to the diagnoses and treatments of vascular anomalies.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Sirolimus | Experimental | Drug: Sirolimus |
Who may qualify
- Ages
- 0 to 18 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (19 listed)
- All patients included in the present research must be diagnosed with one of the following vascular anomalies:
- Patients must be 0 - 18 years of age at the time of study entry.
- Without functional impairment requiring treatment of corticosteroid.
- Organ function requirements:
- Adequate liver function Total bilirubin less than or equal to 1.5 x upper limit of normal (ULN)for age, and alanine transaminase (ALT) and aspartate aminotransferase (AST) less than or equal to 2.5 x upper limit normal (ULN) for age.
Key exclusion criteria (9 listed)
- Allergy to sirolimus or other rapamycin analogues.
- Allergy to sirolimus or other rapamycin analogues.
- Any known evidence of significant local or systemic uncontrolled infection, defined as receiving intravenous antibiotics at the time of randomization.
- Patients must not be known to be Human Immunodeficiency Virus positive or known immunodeficiency. Testing is not required unless a condition is suspected.
- Other concurrent severe and/or uncontrolled medical disease which could compromise participation in the study (e.g. uncontrolled diabetes, uncontrolled hypertension, severe malnutrition, chronic liver or renal disease, active upper gastrointestinal tract ulceration).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| SirolimusAlso: RapamycinSirolimus was initiated at a dosage of 0.8 mg/m2 administered twice daily. Subsequently, the sirolimus dosage was adjusted monthly to achieve trough levels between 10 and 15 ng/mL. | Drug | Sirolimus |
Primary outcome
Volumetric changes in complicated vascular anomalies to sirolimus
Time frame: Baseline, 6, and 12 months
Response to sirolimus treatment was measured by volumetric magnetic resonance imaging (MRI) analyses, which were performed at baseline and 6 and 12 months after treatment and were independently assessed by 2 radiologists. Changes in size of vascular anomalies were classified as further growth (increase of ≥10%), no change (<10% increase and <10% decrease), partial involution (decrease of ≥10% and <75%), nearly complete involution (decrease of ≥75% and <100%), or complete involution (100%). Photographs of the complicated vascular anomalies were taken at months 0, 3, 6 and 12 by a medical photographer. Complete/nearly complete resolution of the vascular anomalies at month 12 compared to baseline based on the intra-patient blinded centralized independent qualitative assessments of month 12 MRI.
The changes in the patient's symptoms and/or complications.
Time frame: Baseline, 3, 6, and 12 months
4 secondary outcomes
Quality of Life in patients by the Pediatric Quality of Life Inventory TM (PedsQLTM) 4.0 Generic Core Scales.
Time frame: Baseline, 6, 12 months
Measuring the impact of vascular anomalies on family functioning by PedsQLTM 4.0 Family Impact Module (FIM).
Time frame: Baseline, 6, 12 months
Frequency of adverse events as assessed by CTCAE v4.0
Time frame: Baseline, 3, 6, 12 months
Changes in plasma levels fibrinogen and/ or D-dimers
Time frame: Baseline, 3, 6, 12 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Mar 2022.
- Derived from this study: PubMed 34082006Ji Y, Chen S, Yang K, Zhou J, Zhang X, Jiang X, Xu X, Lu G, Qiu L, Kong F, Zhang Y. A prospective multicenter study of sirolimus for complicated vascular anomalies. J Vasc Surg. 2021 Nov;74(5):1673-1681.e3. doi: 10.1016/j.jvs.2021.04.071. Epub 2021 May 31.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Yi Ji principal investigator
West China Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Sirolimus in people with Vascular Anomaly, run by West China Hospital at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 19 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 15 Mar 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Volumetric changes in complicated vascular anomalies to sirolimus (time frame: Baseline, 6, and 12 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03583307, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Mar 2022.