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

Sponsor

Children's Hospital of Fudan University (Other)

Overall Status

Recruiting

CT.gov ID

NCT04921722

Collaborator

(none)

Enrollment

Location

Arms

36.3

Anticipated Duration (Months)

2.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Kaposiform Hemangioendothelioma Tufted Angioma Superficial Vascular Anomalies Superficial Lymphatic Malformations	Drug: Percutaneous sirolimus Drug: Oral sirolimus	Phase 4

Detailed Description

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

75 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Single (Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Oct 22, 2021

Anticipated Primary Completion Date :

Nov 1, 2023

Anticipated Study Completion Date :

Nov 1, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Topical use of 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.	Drug: Percutaneous sirolimus 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. Other Names: Rapamycin
Active Comparator: Oral use of 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.	Drug: Oral sirolimus 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. Other Names: Rapamycin

Arm

Intervention/Treatment

Experimental: Topical use of 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.

Drug: Percutaneous sirolimus

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.

Other Names:

Rapamycin

Active Comparator: Oral use of 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.

Drug: Oral sirolimus

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.

Other Names:

Rapamycin

Outcome Measures

Primary Outcome Measures

Effective rate [From admission to follow-up six months]
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.

Secondary Outcome Measures

Changes of resistance coefficient [From admission to follow-up six months]
Measured by ultrosonic doppler flowmetery at follow-up
Incidence of adverse events [From admission to follow-up six months]
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
Platelet count [From admission to follow-up six months]
Platelet count is one of the major indicators of response to treatment. It is supposed to be greater than 100×10^9/L.
Changes of peak blood flow [From admission to follow-up six months]
Measured by ultrosonic doppler flowmetery at follow-up

Eligibility Criteria

Criteria

Ages Eligible for Study:

0 Years to 18 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.