Percutaneous Administration of Sirolimus in the Treatment of Superficial Complicated Vascular Anomalies

Study Overview
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Brief Summary
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In this study, we investigate the safety and efficacy of topical sirolimus in the treatment of superficial complicated vascular anomolies.

Detailed Description
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Vascular anomaly is a kind of rare disease. According to histology, biological behavior and clinical manifestations, it can be divided into two categories: vascular tumor and vascular malformation. mTOR inhibitors are proved with the properties of anti-proliferation and anti-angiogenesis. Therefore, they have been used in the treatment of vascular anomalies. Sirolimus, by its ability to prevent downstream protein synthesis and subsequent cell proliferation and angiogenesis, has become a novel and effective treatment. However, after the children reach complete response, there may still be skin manifestations that affect the appearance and cause psychological shadows. Therefore, intervention is required. Studies have reported that topical sirolimus is effective in treating Kaposiform Hemangioendothelioma (KHE). It is absorbed through the skin, avoiding the first pass elimination effect of the liver. Fewer adverse reactions have been observed. In this study, we investigate the efficacy and safety of percutaneous administration of sirolimus in the treatment of superficial complicated vascular anomalies.

Official Title
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Percutaneous Administration of Sirolimus in the Treatment of Superficial Complicated Vascular Anomalies: a Randomized Controlled Trial

Conditions
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Kaposiform Hemangioendothelioma, Tufted Angioma, Superficial Vascular Anomalies, Superficial Lymphatic Malformations

Intervention / Treatment
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* Drug: Percutaneous sirolimus
* Drug: Oral sirolimus


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participant clinically or pathologically diagnosed with KHE, TA or complicated superficial vascular anomolies involving lymphatic components. The case is initial, with a relatively limited superficial lesion. The participant has residual surface lesions after oral medication. Participant with no use of other medication or surgical treatment Participant with detailed medical records of the disease at the time of screening Participant with signed and dated informed consent from the guardian(s) Exclusion Criteria: Participants with Kasabach-Merritt Phenomenon, with platelets <50×10 9 /L. Participants with general disease such as hypertension, diabetes, adrenal insufficiency, neurological diseases, liver and kidney dysfunction, and cardiopulmonary insufficiency. Participants with other hematological diseases or solid tumor. Participants allergic to sirolimus or dressing.

Ages Eligible for Study
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Minimum Age: 0 Years
Maximum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Topical use of sirolimus<br>Drop 5 ml of sirolimus oral solution and 5 g of dressing into the mixed bottle. Apply mixed gel of topical sirolimus to affected area. Use it twice a day for 6 months. | Drug: Percutaneous sirolimus<br>* We compare topical and oral use of sirolimus in the treatment of superficial complicted vascular anomalies. In experimental group, we administrate percutaneous sirolimus. Drop 5 ml of sirolimus oral solution and 5 g of dressing into the mixed bottle. Apply mixed gel of topical sirolimus to affected area. Use it twice a day for 6 months.<br>* Other names: Rapamycin;|
| Active Comparator: Oral use of sirolimus<br>Oral dose of sirolimus is calculated according to body surface area. Take it twice a day for 6 months. Maintain the blood concentration of sirolimus at 5-15ng/ml. | Drug: Oral sirolimus<br>* We compare topical and oral use of sirolimus in the treatment of superficial complicted vascular anomalies. In active comparator group, we administrate oral sirolimus. Oral dose of sirolimus is calculated according to body surface area. Take it twice a day for 6 months. Maintain the blood concentration of sirolimus at 5-15ng/ml.<br>* Other names: Rapamycin;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Effective rate | Achauer BM et al. made the four-level standard as follows. Grade I: tumor size and skin lesion color regression ≤ 25%; grade II: tumor size and skin lesion color regression 25%-50%; grade III: tumor size and skin lesion color regression 50-75%; grade IV: tumor size and skin lesion color regression ≥75%. After 6 months of treatment, the pzrticipant will be evaluated. Grade I will be viewed as invalid. Grade II and grade III will be viewed as effective, and grade IV will be viewed as very effective. Those in grade Ⅱ, Ⅲ or Ⅳ will be calculated in effectiveness rate. | From admission to follow-up six months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes of resistance coefficient | Measured by ultrosonic doppler flowmetery at follow-up | From admission to follow-up six months | 
| Incidence of adverse events | Adverse events will be reported according to Common Terminology Criteria for Adverse Events, version 4.0 (CTCAE v4.0). Incidence of complications such as oral ulcers, abnormal liver enzymes, infections will be recorded. It is defined as occurring if individual subject has any of the above complications during the 6-month intervention | From admission to follow-up six months | 
| Platelet count | Platelet count is one of the major indicators of response to treatment. It is supposed to be greater than 100×10^9/L. | From admission to follow-up six months | 
| Changes of peak blood flow | Measured by ultrosonic doppler flowmetery at follow-up | From admission to follow-up six months |