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

Phase 4

Recruiting

• Conditions: Kaposiform Hemangioendothelioma; Superficial Lymphatic Malformations; Tufted Angioma; Superficial Vascular Anomalies
• Interventions: Drug: Percutaneous sirolimus; Drug: Oral sirolimus

• Registration Number: NCT04921722
• Lead Sponsor: Children's Hospital of Fudan University

Brief Summary

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

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 Timeline

• Study First Submitted: 2021-06-06
• Study First Submitted QC: 2021-06-06
• Study First Posted: 2021-06-10
• Study Start: 2021-10-22
• Status Verified: 2024-03
• Last Update Submitted: 2024-03-13
• Last Update Posted: 2024-03-15
• Primary Completion: 2025-11-01
• Study Completion: 2025-11-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 75

Inclusion Criteria

• Participant clinically or pathologically diagnosed with KHE, TA or complicated superficial vascular anomolies involving lymphatic components.

  1. The case is initial, with a relatively limited superficial lesion.
  2. 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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Topical use of sirolimus	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.
Oral use of sirolimus	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.

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
Changes of peak blood flow	From admission to follow-up six months	Measured by ultrosonic doppler flowmetery at follow-up
Changes of resistance coefficient	From admission to follow-up six months	Measured by ultrosonic doppler flowmetery at follow-up
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.
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

Trial Locations

Locations (1)

Children's Hospital of Fudan University; 🇨🇳 Shanghai, China