Evaluation of Botulinum TOXin type A in the treatment of Buerger’s disease

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Centre Hospitalier Universitaire De Toulouse

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nutritional and Metabolic Diseases [C18]

Decision date (initial)

2024-10-22

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

No

External identifiers

EU CT number

2024-517772-38-00

EudraCT number

2021-005723-20

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Others

The primary judgment criterion is feasibility. The feasibility criterion corresponds to the number of patients who actually received the planned injections within the defined time limits, among the patients who should have received the injection according to the criteria of the protocol.

Secondary objectives 8

1. Evaluation of the tolerance criterion according to the following parameters: collection of temporary (hematoma, erythema, ecchymosis at the injection site, pain (J0), before/after and during injection) (by EVA) or severe adverse events (muscle weakness, , general muscle weakness or muscle group at distance from injection site, difficulty swallowing, dyspnea, immediate allergic reaction to injections)
2. Critical parameters of hemodynamic ischemia
3. Intensity of the pain assessed by EVA at M1, M3, M6
4. Evaluation of the healing of distal ulcers (J0, M1, M3, M6)
5. Appearance of new digital ulcers (number)
6. Number of the need for minor and major amputation
7. Frequency and severity of Raynaud’s syndrome associated with Buerger’s disease
8. Evaluation of the quality of life (questionnaire EQ-5D-5L, VASCQUOL) at D0 and M6

Conditions and MedDRA coding

Buerger's disease

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. Age ≥ 18 years
2. Patient with Buerger’s disease according to Olin criteria
3. Patient with digital ischemia with critical upper or lower limb ischemia criteria defined as Upper limb: pain and/or trophic disorders for at least 15 days AND digital pressure less than 50 mmHg Or TCPO2 30 mmHg) Or/and Lower limb: pain and/or trophic disorders for at least 15 days AND ankle pressure less than 50 mmHg (70 mmHg if diabetes), or 30 mmHg at the toe (50 mmHg if diabetes) or TCPO2 30 mmHg).
4. Ability to attend study visits
5. Ability to complete daily study agenda
6. Ability to give free and informed consent
7. Membership of a Social Security scheme

Exclusion criteria 15

1. History of myasthenia gravis or Eaton-Lambert syndrome
2. History of inflammatory myositis for less than 2 years or pre-existing motor neuron disease or superior limb neuropathy.
3. Known allergy to botulinum toxin or cream lidocaine, albumin or inhaled nitrous oxide/oxygen.
4. Progressive infection of one hand or foot
5. Aminoglycoside treatment
6. Pregnant or nursing women
7. History of vascular surgery of surgical sympathectomy of upper or lower limb
8. Revascularization procedure considered within 3 months of inclusion
9. Risk of major amputation within 3 months of inclusion
10. Iloprost expected one month before the study treatment
11. Hyperbaric chamber sessions scheduled within one month of study treatment
12. Life expectancy less than 6 months
13. Contraindication to one or more of the following products: BOTOX 100 UNITS ALLERGAN, LIDOCAINE/PRILOCAINE BIOGARAN 5%, cream or NITROUS OXIDE MEDICINAL AIR LIQUIDE
14. Patients treated by class III anti arythmic drugs for exemple amiodarone
15. Patient under guardianship, curatorship, protection of justice

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The primary endpoint is feasibility. The feasibility endpoint corresponds to the number of patients who actually received the planned injections within the defined timeframes, among the patients who should have had the injection according to the protocol criteria.

Secondary endpoints 8

1. Tolerance assessment. The tolerance criterion is assessed according to the practitioner by collecting temporary adverse events that are associated with the specific research procedure and that are expected and by severe adverse events.
2. Evaluation of critical ischemia parameters: Evaluation of tissue perfusion by laser Doppler, toe pressure or digital pressure in mmHg before (D0) and after injection (M1, M3, M6) Evaluation of tissue perfusion by thermal camera before (D0) and after injection (M1, M3, M6) Transcutaneous measurement of partial oxygen pressure TCPO2 before (D0) and after injection (M1, M3, M6)
3. Pain assessment, evaluated by VAS at M1, M3, M6
4. Assessment of healing of distal ulcers (D0, M1, M3, M6) - color scale (% of bud, fibrin, necrosis, epidermization) at D0, M1, M3, M6 - size, surface of ulcers at D0, M1, M3, M6 - new distal ulcerations at D0, M1, M3, M6 - number of ulcers whose surface has reduced by more than 40% at M1, M3, M6 - number of total healing (100% epidermization) at M1, M3, M6 - number of minor or major amputations at M1, M3, M6
5. Appearance of new digital ulcers
6. Need for minor and major amputation
7. Frequency and severity of Raynaud's syndrome associated with Buerger's disease according to the Raynaud condition score (D0, M1, M3, M6) An attack is defined as a paroxysmal episode of pallor or cyanosis to cold (with or without pain, tingling or numbness). Patients will note daily the number and duration of RA attacks as well as the severity of the RA, each attack is self-assessed daily on a 10-point scale and the average calculated over the 14 days
8. Evaluation of quality of life questionnaires (EQ-5D-5L, Cochin, Claus) at D0 and M6

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Centre Hospitalier Universitaire De Toulouse

Sponsor organisation

Centre Hospitalier Universitaire De Toulouse

Address

2 Rue Viguerie

City

Toulouse

Postcode

31300

Country

France

Scientific contact point

Organisation

Centre Hospitalier Universitaire De Toulouse

Contact name

MALLOIZEL DELAUNAY Julie

Public contact point

Organisation

Centre Hospitalier Universitaire De Toulouse

Contact name

TOMASIK Audrey

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 5 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications