Topical Timolol Benefit in Venous Ulcers

NCT ID: NCT02422017

Last Updated: 2025-09-19

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 42 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-04-30
• Study Completion Date: 2018-01-31

Brief Summary

Background: Venous Leg ulcers are a frequent pathology in dermatology and complex in their management. At the origin of high health costs and strong repercussions on quality of life for patients, they require long management and may be subject to possible complications.

In spite of appropriate treatment, 50-60% of these ulcers are not healed at 24 weeks.

Purpose: Topical beta adrenergic antagonists have shown efficacy in wound healing. The purpose of this study is to evaluate the efficacy and safety of treatment of chronic venous ulcers with topical timolol.

Detailed Description

Abstract: Complicating severe stages of chronic venous insufficiency, venous leg ulcers are common in dermatology and responsible for important health care costs. Healing remains long with many persistent cases after one year, despite compression and local dressings. Several pharmacological studies have demonstrated a benefit of beta-blockers on the wound healing process: present in the skin, the beta-adrenergic receptors play a role in wound healing. Their stimulation inhibits healing while blocking them promotes angiogenesis, fibroblast migration and keratinocyte migration. Using the topical timolol in several patients seems to confirm these effects: all ulcers treated with timolol healed in a few weeks whereas they did not evolve under local care and compression.

The purpose of this study is to demonstrate whether there is an interest in topical timolol for venous leg ulcers in combination with compression and wound dressings versus placebo. The primary endpoint is to evaluate the healing rate to W12. The effects will be evaluated with photography, evaluation of the surface of the ulcer at W12 compared to W0. The research of side effects will also be evaluated.

Conditions

Venous Leg Ulcers

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Timolol

Patients will receive one drop of timolol every 6cm ² every other day for twelve weeks in combination with dressings and compression.

Group Type: EXPERIMENTAL

Timolol

Intervention Type: DRUG

Patients will receive one drop of timolol every 6cm ² every other day for twelve weeks applied on the ulcer of interest

Local care treatment

Intervention Type: OTHER

Local care treatment with dressing compression in accordance with standards applied every other day

Control

Local care treatment only (dressing and compression applied every other day)

Group Type: OTHER

Local care treatment

Intervention Type: OTHER

Local care treatment with dressing compression in accordance with standards applied every other day

Interventions

Timolol

Patients will receive one drop of timolol every 6cm ² every other day for twelve weeks applied on the ulcer of interest

Intervention Type: DRUG

Local care treatment

Local care treatment with dressing compression in accordance with standards applied every other day

Intervention Type: OTHER

Other Intervention Names

Timoptol

Eligibility Criteria

Inclusion Criteria

• Affiliated to a social security scheme patients
• Informed consent
• Patients over 18 years
• Ulcer lasting for at least 24 weeks with no improvement observed after 4 weeks of well conducted treatment (compression and local care)
• Presence of one or more venous leg ulcers (objectified by a Doppler ultrasound dated within 6 months and ABPI ≥ 0.8)
• Ulcers with a surface of 5 to 50 cm ² and at granulation stage
• Study ulcer must be at least 2 cm from Any Other ulcer on same extremity.
• If several ulcers present, the greatest is selected
• Granulation tissue ≥ 50%

• Non-cardioselective beta-blocker treatment
• Bradycardiac treatment
• Patients under diltiazem, verapamil (calcium antagonists)
• Reaching underlying noble structures, tumor acutisation wound
• Immunosuppression
• Diabetes unbalanced (HbA1c> 8%)
• Severe Malnutrition (albumin <25g / L)
• Anemia <10g/dl
• Contraindication to beta-blockers

Exclusion Criteria

• Minors under guardianship, deprived of liberty, not looking at treatment, lack of signed consent, pregnant women, demented patients
• Ulcer lasting for less than 24 weeks
• Granulation tissue <50%
• Obliterative arteritis (ABPI <0.8)

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Centre Hospitalier Universitaire, Amiens

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

CHU Amiens

Amiens, , France

Countries

France

References

Baltazard T, Senet P, Momar D, Picard C, Joachim C, Adas A, Lok C, Chaby G. Evaluation of timolol maleate gel for management of hard-to-heal chronic venous leg ulcers. Phase II randomised-controlled study. Ann Dermatol Venereol. 2021 Dec;148(4):228-232. doi: 10.1016/j.annder.2020.11.009. Epub 2021 Feb 4.

Reference Type: RESULT

PMID: 33551214 (View on PubMed)

Other Identifiers

2014-005046-22

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

PI2014_843_0022

Identifier Type: -

Identifier Source: org_study_id