Overview
Sponsor-declared trial summary
Phase
Therapeutic confirmatory (Phase III)
Status
Authorised, recruitment pending
Participants planned
34
Countries
1
Sites
7
Thrombotic episodes in superficial venous malformations in children
To evaluate the efficacy of per os acetylsalicylic acid versus placebo, in addition to a local non-steroidal anti-inflammatory drug, on the pain associated with superficial venous thrombosis in children with superficial venous malformations
Key facts
- Sponsor
- Centre Hospitalier Regional Universitaire De Tours
- Participant type
- Pediatric, Patients
- Age range
- 0-17 years, 18-64 years
- Gender
- Male and Female
- Therapeutic area
- Diseases [C] - Cardiovascular Diseases [C14]
- Decision date (initial)
- 2026-02-25
- Transition trial
- No
- Low-intervention
- No
- Rare-disease indication
- Yes
- Vulnerable population
- Yes
Trial design
CTIS Part I — objectives, methods, condition coding
Main objective
Scope: Therapy, Efficacy
To evaluate the efficacy of per os acetylsalicylic acid versus placebo, in addition to a local non-steroidal anti-inflammatory drug, on the pain associated with superficial venous thrombosis in children with superficial venous malformations
Secondary objectives 6
- Assessing the efficacy of per os acetylsalicylic acid in reducing painkiller consumption
- Impact on the child's quality of life
- Assessing the tolerability of oral acetylsalicylic acid in addition to a local non-steroidal anti-inflammatory drug
- To evaluate the impact of experimental and control treatments on coagulation markers during attacks of superficial venous thrombosis in superficial venous malformations
- Evaluate the efficacy of oral acetylsalicylic acid on sleep quality
- Evaluate the efficacy of oral acetylsalicylic acid on functional impotence related to malformation
Conditions and MedDRA coding
Thrombotic episodes in superficial venous malformations in children
| Version | Level | Code | Term | System organ class |
|---|---|---|---|---|
| 24.1 | LLT | 10043643 | Thrombosis venous superficial | 10047065 |
| 26.0 | PT | 10025532 | Malformation venous | 100000004850 |
Study design 3 periods
| # | Title | Allocation | Blinding | Roles blinded | Arms |
|---|---|---|---|---|---|
| 1 | Participant selection A screening will be conducted to identify patients with superficial venous malformation confirmed by imaging with the presence of phleboliths, who have had at least two episodes of superficial vascular thrombosis in the previous 12 months and who meet the eligibility criteria.
|
Not Applicable | None | ||
| 2 | Recruitment (inclusion) and randomisation Patients will then be recruited during outpatient consultations in dermatology, interventional radiology, surgery, or, above all, during multidisciplinary consultations dedicated to vascular malformations. Verbal information will be provided, and written information will be given again. The investigator will inform patients/parents of their rights regarding research involving human subjects that does not fall within the scope of routine care. He will obtain the signature of both parents (or legal guardians) on the consent form, as well as the child's assent. Children will be included and randomized for the order of treatment administration (crossover).
|
Randomised Controlled | Double | [{"id":166635,"code":2,"name":"Investigator"},{"id":166634,"code":1,"name":"Subject"}] | Arm 1 - Aspirine + gel, then Placebo + gel: Randomization will determine the order in which treatments are administered. In this first scenario, the patient will receive aspirin (acetylsalicylic acid) + gel during his first episode, then a placebo + gel during his second episode. Arm 2 - Placebo + gel, then Aspirine + gel: Randomization will determine the order in which treatments are administered. In this second scenario, the patient will receive a placebo + gel during his first episode, then aspirin (acetylsalicylic acid) + gel during his second episode. |
| 3 | Follow-up assessments and visit 2 study visits are planed : the first one after the first episode of TVS (D15 to D30) and the second one after the second episode.
During the study, parents will be contacted once a month by the coordinating research nurse at each center to reinforce adherence to the protocol and ensure that the study is running smoothly.
Each patient will be included a priori for up to two epidoes (flare-ups), for a maximum period of 24 months (but which may be much shorter). If the two TVS flare-ups occur within the first 12 months, the patient will be offered the option of continuing the study for the next two flare-ups (four in total, maximum), in order to increase the power of the study, or of ending the study. If the study is scheduled to continue for two new flare-ups, the third and fourth follow-up consultations will take place in the same way.
If the patient has not had any TVS episode, or has had only one episode, an end-of-study visit will be conducted to collect data from the patient diary and treatment records. This visit will take place during a routine follow-up visit for these patients.
|
Not Applicable | None |
Eligibility criteria
Principal inclusion / exclusion criteria as submitted by sponsor
Inclusion criteria 7
- Patients aged 6 to 17 included
- Weight ≥ 20 kg
- Isolated or combined superficial venous malformation, whatever the topography, confirmed by imaging (MRI, CT, Doppler ultrasound), 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 21
- Patients with deep or syndromic venous malformation
- Patients with galactose intolerance, Lapp lactase deficiency or glucose or galactose malabsorption syndrome
- History of peptic ulcer disease or chronic gastritis
- History of asthma, angioedema, urticaria, or acute rhinitis triggered by diclofenac, acetylsalicylic acid, or other nonsteroidal anti-inflammatory drugs
- Allergy to one of the excipients of diclofenac gel
- 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
- 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
- Known allergy to NSAIDs
- Patient with Klippel-Trenaunay syndrome or Cloves syndrome
Endpoints
Primary and secondary outcome measures (English text)
Primary endpoints 1
- Evaluation of the efficacy on pain of acetylsalicylic acid + local NSAID versus placebo + local NSAID, administered for a period of 3 days to 14 days
Secondary endpoints 6
- Cumulative consumption of tier 1 and 2 analgesics (indirect reflection of treatment efficacy) over 14 days
- Impact on the child's quality of life (by measuring the C-DLQI - Children-Quality of Life Index and the CLFMQol - specific Quality Of Life measurement tool for Children with Low-Flow Malformations) at baseline, and after each attack
- Safety: number of serious and non-serious adverse events in each group
- Comparison of the impact of experimental treatment and control treatment on coagulation markers during attacks of superficial venous thrombosis in superficial venous malformations, by measuring : CBC, PT, APTT, plasma fibrinogen and D-dimers
- Impact of the malformation on sleep quality (Fast Score SLEEP VASC) measured once a day for 14 days
- Functional impairment related to the malformation will be assessed daily using a VAS (visual analog scale, ranging from 0 to 10) (0 no discomfort, 10 maximum discomfort, inability to move a limb or body segment) at baseline and after each follow-up.
Investigational products
Investigational medicinal products (IMPs), comparators, placebo, auxiliary
Test 1
PRD408097 · Product
- Active substance
- Acetylsalicylic Acid
- Substance synonyms
- ASPIRIN, ACETYLSALICYLIC ACID (ASA), ACIDUM ACETYLSALICYLICUM
- Pharmaceutical form
- TABLET
- Route of administration
- ORAL
- Max daily dose
- 1920 mg milligram(s)
- Max total dose
- 26880 mg milligram(s)
- Max treatment duration
- 14 Day(s)
- Authorisation status
- Authorised
- ATC code
- N02BA01 — ACETYLSALICYLIC ACID
- Marketing authorisation
- 34009 300 781 8 1
- MA holder
- BAYER HEALTHCARE
- MA country
- France
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Placebo 1
Calcium Hydrogen Phosphate Dihydrate
SUB11771MIG · Substance
- Active substance
- Calcium Hydrogen Phosphate Dihydrate
- Pharmaceutical form
- FILM-COATED TABLET
- Route of administration
- ORAL
- Max daily dose
- 1920 mg milligram(s)
- Max total dose
- 26880 mg milligram(s)
- Max treatment duration
- 14 Day(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Auxiliary 1
DICLOFENAC ARROW 1 %, gel en flacon pressurisé
PRD5686380 · Product
- Active substance
- Diclofenac Diethylamine
- Pharmaceutical form
- GEL
- Route of administration
- CUTANEOUS USE
- Max daily dose
- 2 g gram(s)
- Max total dose
- 28 g gram(s)
- Max treatment duration
- 14 Day(s)
- Authorisation status
- Authorised
- ATC code
- M02AA15 — DICLOFENAC
- Marketing authorisation
- 65460224
- MA holder
- ARROW GENERIQUES
- MA country
- France
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Sponsors and contacts
Sponsor organisations, regulatory contacts, third parties
Centre Hospitalier Regional Universitaire De Tours
- Sponsor organisation
- Centre Hospitalier Regional Universitaire De Tours
- Address
- 2 Boulevard Tonnelle
- City
- Tours Cedex 9
- Postcode
- 37044
- Country
- France
Scientific contact point
- Organisation
- Centre Hospitalier Regional Universitaire De Tours
- Contact name
- Sophie LEDUCQ
Public contact point
- Organisation
- Centre Hospitalier Regional Universitaire De Tours
- Contact name
- Sophie LEDUCQ
Locations
1 EU/EEA country · 7 investigational sites
By country
| Country | MS status | Planned subjects | Sites |
|---|---|---|---|
| France | Authorised, recruitment pending | 34 | 7 |
| Rest of world | — | 0 | — |
Investigational sites
Hopital Necker Enfants Malades
Dermatology, 149 Rue De Sevres, 75015, Paris
Centre Hospitalier Regional De Marseille
Dermatology, 264 Rue Saint Pierre, 13005, Marseille
Centre Hospitalier Regional D'Angers
Dermatology, 4 Rue Larrey, 49100, Angers
Centre Hospitalier Regional Universitaire De Tours
Dermatology, 49 Boulevard Beranger, 37000, Tours
Centre Hospitalier Regional Et Universitaire De Brest
Dermatology, 2 Avenue Marechal Foch, 29200, Brest
Centre Hospitalier Universitaire De Nantes
Dermatology, 1 Place Alexis Ricordeau, 44000, Nantes
Centre Hospitalier Universitaire De Rennes
Dermatology, 2 Rue Henri Le Guilloux, 35033, Rennes Cedex 9
Results and documents
Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial
Documents 30 files
Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.
| Type | Title | Version |
|---|---|---|
| Protocol (for publication) | D1_Protocol 2024-517595-38-00 | 1.1 |
| Protocol (for publication) | D1_Protocol 2024-517595-38-00_TC | 1.1 |
| Protocol (for publication) | D4_Patient facing document Patient card | 1.0 |
| Protocol (for publication) | D4_Patient facing document Patient diary | 1.1 |
| Protocol (for publication) | D4_Patient facing document Patient diary_TC | 1.1 |
| Protocol (for publication) | D4_Patient facing document Tutorial without voice-over | 1.0 |
| Recruitment arrangements (for publication) | D4_Patient facing document Patient card | 1.0 |
| Recruitment arrangements (for publication) | D4_Patient facing document Patient diary | 1.1 |
| Recruitment arrangements (for publication) | D4_Patient facing document Patient diary_TC | 1.1 |
| Recruitment arrangements (for publication) | D4_Patient facing document Tutorial without voice-over | 1.0 |
| Recruitment arrangements (for publication) | K1_Recruitement arrangements 2024-517595-38-00-FR | 2.0 |
| Recruitment arrangements (for publication) | K1_Recruitement arrangements_2024-517595-38-00-FR_TC | 2.0 |
| Recruitment arrangements (for publication) | K2_Document_additionnel 2024-517595-38-00 | 1.0 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF 11-14 years old | 1.1 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF 11-14 years old_TC | 1.1 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF 15-17 years old | 1.2 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF 15-17 years old_TC | 1.2 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF 18 years old | 1.2 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF 18 years old_TC | 1.2 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF 6-10 years old | 1.1 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF 6-10 years old_TC | 1.1 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF child following | 1.2 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF child following_TC | 1.2 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF parents | 1.2 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF parents_TC | 1.2 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF pregnency following | 1.3 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF pregnency following_TC | 1.3 |
| Summary of Product Characteristics (SmPC) (for publication) | G2_SmPC aspro320mg | 1 |
| Synopsis of the protocol (for publication) | D1_Protocol synopsis_FR 2024-517595-38-00 | 1.1 |
| Synopsis of the protocol (for publication) | D1_Protocol synopsis_FR 2024-517595-38-00_TC | 1.1 |
Application history
1 submissions — initial application plus substantial / non-substantial modifications
| # | Type | Code | Submitted | Reference MS | Conclusion | Decision date |
|---|---|---|---|---|---|---|
| 1 | INITIAL | IN | 2025-10-28 | France | Acceptable 2026-02-20
|
2026-02-25 |