Acetylsalicylic Acid Versus Placebo as an add-on Treatment to Local Non-steroidal Anti-inflammatory Drug for the Management of Thrombotic Episodes in Superficial Venous Malformations in Children Aged 6 to 17 Years. (ASPIRIN)

Acetylsalicylic Acid Versus Placebo as an add-on Treatment to Local Non-steroidal Anti-inflammatory Drug for the Management of Thrombotic Episodes in Superficial Venous Malformations in Children Aged 6 to 17 Years: a Controlled Randomised, Double-blind, Cross-over, Multicenter Trial

Superficial venous malformations (SVMs) are rare congenital anomalies that present as bluish masses. These masses may be focal, with limited skin involvement, or segmental, with more extensive involvement. They may be associated with syndromic conditions such as blue rubber nevus syndrome.

SVMs are characterised by a progressive worsening course, with repeated episodes of superficial venous thrombosis occurring. These episodes become more frequent over time, causing acute, intense and often highly debilitating pain.

To limit progression and in cases of functional impairment, long-term treatments may be offered. These include venous compression, targeted therapies such as mTOR inhibitors, and, where possible, surgical treatment or sclerotherapy.

However, the management of intra-SVM superficial venous thrombosis is not currently standardised, especially in the pediatric population. This study aims to evaluate the benefits of Acetylsalicylic acid (ASA) as an add-on treatment to local non-steroidal anti-inflammatory drug for the management of thrombotic episodes in superficial venous malformations in children aged 6 to 17 years.

Study Overview

• Status: Not yet recruiting
• Conditions: Venous Malformations; Venous Malformation, Low Flow
• Intervention / Treatment: Drug: AAS at anti-inflammatory doses from 3 days to 14 days.; Drug: Placebo from 3 days to 14 days.; Drug: Application of Diclofenac gel 1% twice a day

• Study Type: Interventional
• Enrollment (Estimated): 34
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Sophie LEDUCQ, MD, PhD; Phone Number: +332 47 47 56 02; Email: S.LEDUCQ@chu-tours.fr
• Study Contact Backup: Name: Coralie TAILLEBUIS; Email: cpcq@chu-tours.fr

Study Locations

• France
  • Angers, France
    • Centre Hospitalier Universitaire d'Angers
    • Contact: Ludovic MARTIN; Phone Number: +332 41 35 34 19; Email: lumartin@chu-angers.fr
  • Brest, France
    • Centre Hospitalier Universitaire de Brest
    • Contact: Claire ABASQ-THOMAS; Phone Number: +332 98 22 33 15; Email: claire.abasq@chu-brest.fr
  • Marseille, France
    • AP-HM
    • Contact: Stéphanie MALLET; Phone Number: +334 91 38 88 01; Email: Stephanie.MALLET@ap-hm.fr
  • Nantes, France
    • Centre Hospitalier Universitaire de Nantes
    • Contact: Sébastien BARBAROT, MD; Phone Number: +332 40 08 40 86; Email: sebastien.barbarot@chu-nantes.fr
  • Paris, France
    • AP-HP
    • Contact: Olivia BOCCARA; Phone Number: +331 44 49 46 63; Email: olivia.boccara@aphp.fr
  • Rennes, France
    • Centre Hospitalier Universitaire de Rennes
    • Contact: Catherine DROITCOURT; Phone Number: +332 99 28 98 89; Email: catherine.droitcourt@chu-rennes.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patients aged 6 to 17 years
• Weight ≥ 20 kg
• Isolated or combined superficial venous malformation, confirmed by imaging, with the presence of phleboliths indicating the occurrence of previous superficial venous thrombosis
• Complicated by acute thrombotic episodes (2 or more in the previous 12 months)
• Written consent of the child's legal representatives or of the participant if over 18 years of age
• Affiliation of a social security scheme
• Highly effective contraception for young women of childbearing age

Exclusion Criteria:

• Patients with deep or syndromic venous malformation
• Patients with known G6PD deficiency
• Patients with known mastocytosis
• History of hemarthrosis
• Simultaneous participation in another biomedical study
• Constitutional or acquired haemostasis pathology
• Current treatment affecting haemostasis (anticoagulants, platelet anti aggregants, oral NSAIDs)
• Frequent bleeding (epistaxis, other) requiring management
• Basic treatment of venous malformation (mTOR inhibitor)
• Active neoplasia or infection (altered coagulation balance)
• Known allergy to acetylsalicylic acid
• Injured skin, whatever the lesion: oozing dermatitis, eczema, infected lesions, burns or wounds
• Pregnant and breastfeeding women
• Severe renal insufficiency, severe hepatic insufficiency, severe uncontrolled cardiac insufficiency
• Methotrexate ≥ 20 mg/week

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: ASA + local NSAID then placebo + local NSAIDs; This is a cross-over design. Patients randomized in this sequence will receive ASA + local NSAIDs during their first flare-up, then placebo + local NSAIDs during their second flare-up (with a wash out period of two weeks).	Drug: AAS at anti-inflammatory doses from 3 days to 14 days.; AAS at anti-inflammatory doses administered orally for a minimum of 3 days and a maximum of 14 days. Orally administered AAS is combined with the application of 1% diclofenac gel (NSAID) twice a day.; Drug: Placebo from 3 days to 14 days.; Placebo administered orally for a minimum of 3 days and a maximum of 14 days. Oral placebo is combined with the application of 1% diclofenac gel (NSAID) twice a day.; Drug: Application of Diclofenac gel 1% twice a day; Application of 1% diclofenac gel (NSAID) twice a day.
Other: Placebo + local NSAID then AAS + local NSAIDs; This is a cross-over design. Patients randomized in this sequence will receive placebo + local NSAIDs during their first flare-up, then AAS + local NSAIDs during their second flare-up (with a wash out period of two weeks).	Drug: AAS at anti-inflammatory doses from 3 days to 14 days.; AAS at anti-inflammatory doses administered orally for a minimum of 3 days and a maximum of 14 days. Orally administered AAS is combined with the application of 1% diclofenac gel (NSAID) twice a day.; Drug: Placebo from 3 days to 14 days.; Placebo administered orally for a minimum of 3 days and a maximum of 14 days. Oral placebo is combined with the application of 1% diclofenac gel (NSAID) twice a day.; Drug: Application of Diclofenac gel 1% twice a day; Application of 1% diclofenac gel (NSAID) twice a day.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The primary criterion is the total pain experienced during the episode, reflecting both intensity and duration.	Pain intensity will be measured using a visual analog scale (VAS) ranging from 0 (no pain) to 10 (the most intense pain imaginable). The child will self-assess their pain, with a parent's help if necessary, twice a day (morning and evening). The area under the EVA-time curve is calculated using the trapezoidal method based on the available values over the duration of the episode.	The first measurement is defined as the start of treatment following the onset of pain reported by the child. VAS data will be collected until the child has a VAS of 0 for two consecutive days, or for up to 14 days.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Total consumption of analgesics	Total consumption of analgesics over the 14-day period. Each day, parents will record in a patient logbook, in addition to the pain VAS score, all medication doses (study medications and others)	Over the 14-day period after the start of treatment
Child's quality of life	Child's quality of life as measured by the C-DLQI [Children's Dematology Quality of Life Index] scoring from 0 to 30, 0-1 = no effect on child's life · 2-6 = small effect · 7-12 = moderate effect · 13-18 = very large effect · 19-30 = extremely large effect.	At baseline and 2 weeks after the start of the treatment;
Child's quality of life	Child's quality of life measured by the CLFMQol [Specific Quality of Life Questionnaire for Slow-Flow Vascular Malformations] including 15 items, with a total score ranging from 0 to 45, 0 being the worst value and 45 the best value.	At baseline and 2 weeks after the start of the treatment;
Sleep quality	Fast Score SLEEP VASC a scale scoring from 0 to 10, 10 being the best sleep quality	Measured once a day for 14 days
Functional impairment	Functional impairment related to the malformation will be assessed using a VAS ranging from 0 to 10 (0 = no discomfort, 10 = maximum discomfort; inability to move a limb or body segment)	Daily over 14 days, at baseline and 2 weeks after the start of the treatment;
Coagulation markers: Hemoglobin	Hemoglobin	At baseline, within 72 hours after the start of the treatment, and 2 weeks after the start of the treatment
Coagulation markers: Platelets	Platelets	At baseline, within 72 hours after the start of the treatment, and 2 weeks after the start of the treatment
Coagulation markers: Prothrombin time	Prothrombin time	At baseline, within 72 hours after the start of the treatment, and 2 weeks after the start of the treatment
Coagulation markers: Activated partial thromboplastin time	Activated partial thromboplastin time	At baseline, within 72 hours after the start of the treatment, and 2 weeks after the start of the treatment
Coagulation markers: Fibrinogen	Fibrinogen	At baseline, within 72 hours after the start of the treatment, and 2 weeks after the start of the treatment
Coagulation markers: D-dimer	D-dimer	At baseline, within 72 hours after the start of the treatment, and 2 weeks after the start of the treatment
Coagulation markers: Factor V	Factor V	At baseline, within 72 hours after the start of the treatment, and 2 weeks after the start of the treatment

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Tolerability: Serious and non-serious adverse events	Number of serious and non-serious adverse events	Through study completion, an average of 2 years

Collaborators and Investigators

• Sponsor: University Hospital, Tours

Study record dates

Study Major Dates

• Study Start (Estimated): September 1, 2026
• Primary Completion (Estimated): September 1, 2030
• Study Completion (Estimated): October 31, 2030

Study Registration Dates

• First Submitted: May 26, 2026
• First Submitted That Met QC Criteria: June 16, 2026
• First Posted (Actual): June 23, 2026

Study Record Updates

• Last Update Posted (Actual): June 23, 2026
• Last Update Submitted That Met QC Criteria: June 16, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: acetylsalicylic acid; superficial venous thrombosis; superficial venous malformations
• Other Study ID Numbers: DR200086; 2024-517595-38-00 (Ctis)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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