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

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

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

Study Overview

• Status: Recruiting
• Conditions: Kaposiform Hemangioendothelioma; Tufted Angioma; Superficial Vascular Anomalies; Superficial Lymphatic Malformations
• Intervention / Treatment: Drug: Percutaneous sirolimus; Drug: Oral sirolimus

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 Type: Interventional
• Enrollment (Estimated): 75
• Phase: Phase 4

Contacts and Locations

Study Locations

• China
  • Shanghai, China, 210012
    • Recruiting
    • Children's Hospital of Fudan University
    • Sub-Investigator: Yingjing Ding, MD
    • Sub-Investigator: Hanlei Yan, MD
    • Contact: Kai Li, MD, PhD; Phone Number: +86 02164931114; Email: likai2727@163.com
    • Principal Investigator: Kai Li, MD, PhD
    • Sub-Investigator: Weili Yan, MD,PhD
    • Sub-Investigator: Ying Gong, MD,PhD
    • Sub-Investigator: Wei Yao, MD, PhD
    • Sub-Investigator: Zuopeng Wang, MD,PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 second to 18 years (Child, Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / 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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Children's Hospital of Fudan University

Study record dates

Study Major Dates

• Study Start (Actual): October 22, 2021
• Primary Completion (Estimated): November 1, 2025
• Study Completion (Estimated): November 1, 2025

Study Registration Dates

• First Submitted: June 6, 2021
• First Submitted That Met QC Criteria: June 6, 2021
• First Posted (Actual): June 10, 2021

Study Record Updates

• Last Update Posted (Actual): March 15, 2024
• Last Update Submitted That Met QC Criteria: March 13, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphatic Diseases; Cardiovascular Abnormalities; Hemangioma; Neoplasms, Vascular Tissue; Lymphatic Vessel Tumors; Congenital Abnormalities; Hemangioendothelioma; Vascular Malformations; Lymphangioma; Lymphatic Abnormalities; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Anti-Bacterial Agents; Protein Kinase Inhibitors; Antibiotics, Antineoplastic; Antifungal Agents; Sirolimus; Temsirolimus; MTOR Inhibitors
• Other Study ID Numbers: LK210106

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No