Efficacy and Safety of Timolol for TKI Induced Paronychia

Study Overview
=================
Brief Summary
-----------------
This study would assess the clinical efficacy of add-on topical timolol 0.5% gel to betamethasone valerate 0.1% for the treatment of EGFR-TKI induced paronychia. Eligible patients, who develop paronychia (affecting fingernails, toenails or both), will be included in this study. They will be randomized in 1:1 ratio using computer-generated randomization list to receive either combination of topical timolol 0.5% gel and betamethasone valerate 0.1% lotion application twice daily or betamethasone valerate 0.1% lotion application twice daily. Patients in timolol combination treatment group will receive topical timolol 0.5% gel twice daily with occlusion (i.e. covered with adhesive badge) and betamethasone valerate 0.1% lotion twice daily with occlsuion for 1 month. Patients in routine arm would receive the management according to routine clinical practice, including prescription of betamethasone valerate 0.1% lotion twice daily for 1 month with occlusion. For patients who do not have paronychia completely resolved after 4 weeks, the treatment assigned will be continued for another 4 to 8 weeks , up to 12 weeks to see the effect.

Detailed Description
-----------------
The aim of this study ist o assess the clinical efficacy of add-on topical timolol 0.5% gel to betamethasone valerate 0.1% for the treatment of EGFR-TKI induced paronychia.

Official Title
-----------------
Efficacy and Safety of add-on Topical Timolol in the Management of Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor-induced Paronychia: A Prospective Randomized Open-labelled Trial

Conditions
-----------------
Paronychia

Intervention / Treatment
-----------------
* Drug: Topical Timolol
* Drug: Betamethasone Valerate


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Aged 18 years or above, either males or females. Received EGFR-TKI, namely gefitinib, erlotinib, afatinib, osimertinib, amivantamab, dacomitinib and mobocertinib. Paronychia (fingernails, toenails, or both) as an adverse event from EGFR-TKI use. Written informed consent obtained from patient. Exclusion Criteria: Age below18. Patients who are allergic to, or contraindicated to topical timolol use. Pregnant women or nursing mother. Non-consenting patients.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: 40 Adult patients aged 18 or above who received EGFR-TKI for the treatment of NSCLC, who develop paronychia (affecting fingernails, toenails or both), will be included in this study. Patients will be randomized in 1:1 ratio using computer-generated randomization list.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Timolol combination treatment<br>Patients will received topical timolol 0.5% eye drops (liquid form) twice daily with occlusion (i.e. covered with adhesive badge) and betamethasone valerate 0.1% cream twice daily with occlsuion for 1 month | Drug: Topical Timolol<br>* Topical timolol 0.5% eye drops (liquid form) twice daily with occlusion (i.e. covered with adhesive badge) and betamethasone valerate 0.1% cream twice daily with occlsuion for 1 month.<br>|
| Active Comparator: Routine arm<br>Patients in routine arm would receive the management according to routine clinical practice, including prescription of betamethasone valerate 0.1% cream twice daily for 1 month with occlusion. | Drug: Betamethasone Valerate<br>* Betamethasone valerate 0.1% cream application twice daily<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The difference in the proportion of patients achieved complete response (disappearance of the lesion, absent pain, and/or bleeding) | The primary outcome of this study is the proportion of patients achieved complete response (disappearance of the lesion, absent pain, and/or bleeding) on topical timolol 0.5% eye drops as compared to betamethasone valerate 0.1% cream. | From baseline to month 3 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The proportion of patients achieved complete or partial response | Proportion of patients achieved complete or partial response (improvement in at least 1 of these 3 items) | From baseline to month 3 | 
| Lack of response as well as proportion of patients with reduced severity of paronychia | Proportion of patients lack of response (improvement in less than 1 item) | From baseline to month 3 | 
| Change in chronic paronychia severity index scale with treatment | Involvement of 1 nail fold = 1; involvement of 2 nail folds [proximal or/and lateral] = 2; bilateral lateral nail fold involvement and proximal nail fold involvement = 3), edema (absent = 0; mild = 1; moderate = 2; severe = 3), erythema (absent = 0; mild = 1; moderate = 2; severe = 3), nail plate changes (absent = 0; mild = 1; moderate = 2; severe = 3), and cuticle involvement (normal = 0; damaged = 1; absent = 2), producing a combined total score (between 0 [min.] and 14 [max.] | From baseline to month 3 | 
| The improvement of paronychia by 4 point scale | 1: 0 to <30% , 2: 30 to <50% ,3: 50 to 75% ,4: 75 to 100 % improvement) | From baseline to month 3 | 
| Change in severity of pain by Visual Analog Scale | VAS scores ≤3.4cm corresponded to mild pain-related interference with functioning, scores of 3.5-6.4 to moderate interference, and scores ≥6.5 to severe interference. | From baseline to month 3 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
EGFR TKI, Paronychia, Timolol