The Efficacy of Topical Timolol Combined With Cryotherapy in EGFR Inhibitors-induced Paronychia - a Double-blinded, Intrapatient Left-to-right Controlled Study

May 1, 2023 updated by: Huang Yu Chen, Taipei Medical University WanFang Hospital

The Efficacy of Topical Timolol Combined With Cryotherapy in EGFR Inhibitor-induced Paronychia - a Double-blinded, Intrapatient Left-to-right Controlled Study

Background: EGFR inhibitors (EGFRi) have been used to treat a wide variety of cancers nowadays. One of the major side effects of EGFRi is paronychia, which was not fatal but may caused huge negative impact on patient's daily activities. Current guidelines regarding EGFRi-induced paronychia suggested treatment with cryotherapy, topical corticosteroid or surgical intervention for Common Terminology Criteria for Adverse Events (CTCAE) grade 2 to grade 3 lesions. Recent studies showed that topical beta-blockers may be effective treatment for EGFRi- induced paronychia. However, the evidence was limited to case series and there was no randomized trials evaluating the efficacy.

Goal: To evaluate whether topical timolol combined with cryotherapy was more effective than cryotherapy alone in treating EGFR inhibitors-induced paronychia.

Method: In this single center, randomized, double-blinded, left-to-right comparison study, we plan to enroll 35 patients with EGFR inhibitors-induced paronychia. Patients eligible to enter this study should be over the age of 20 having at least one finger or toe involved with CTCAE grade 2~3 paronychia on each of their hands or feet. The paronychia should have no indication for surgical treatment. After enrollment, one physician will randomize the hands or feet to either timolol-plus-cryotherapy group or cryotherapy-alone group using a computer-generated random allocation scheme. The side allocated to the timolol-plus-cryotherapy group will receive topical timolol solution twice daily (since the beginning of the allocation and continue for 8 weeks) and topical cryotherapy with liquid nitrogen every other week (at the allocation day, at the 2nd week, 4th week and 6th week after the beginning of the trial). The other side allocated to cryotherapy-alone group will receive placebo (normal saline) twice daily (since the beginning of the allocation and continue for 8 weeks) and topical cryotherapy with liquid nitrogen every other week (at the allocation day, at the 2nd week, 4th week and 6th week after the beginning of the trial). In the treatment phase, patients may receive additional local or systemic antibiotics according to the dermatologist's clinical judgement, but they can not receive topical silver nitrate, trichloroacetic acid or corticosteroid ointment. Patients are evaluated at baseline, at 2, 4, 6 and 8 weeks after the initiation of treatment. Efficacy endpoints include CTCAE grade, scoring system for paronychia related to oncologic treatments (SPOT) and physician global assessment, which are evaluated by a blinded investigator based on digital photos, and pain VAS score and patient global assessment, which are evaluated by questionnaire to the patients.

Study Overview

Study Type

Interventional

Enrollment (Actual)

8

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

      • Taipei, Taiwan
        • Taipei Municipal Wan-Fang Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

20 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • EGFR inhibitors-induced paronychia
  • Older than 20 years
  • Having at least one finger or toe involved with CTCAE grade 2~3 paronychia on each of their hands or feet

Exclusion Criteria:

  • Indication for surgical treatment
  • Medical history of asthma, severe COPD, sinus bradycardia, SA block, 2nd to 3rd degree AV conduction delay, heart failure, cariogenic shock or allergy to timolol

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Timolol plus cryotherapy
Apply topical timolol solution twice daily (since the beginning of the allocation and continue for 8 weeks) and cryotherapy with liquid nitrogen once every other week (on the allocation day, at the 2nd week, 4th week and 6th week after the beginning of the trial).
Apply on affected finger or toes twice daily for 8 weeks
Other Names:
  • Timoptol
Conducted on affected finger or toes every other week for four sessions.
Placebo Comparator: Placebo plus cryotherapy
Apply placebo (normal saline) twice daily (since the beginning of the allocation and continue for 8 weeks) and cryotherapy with liquid nitrogen once every other week (on the allocation day, at the 2nd week, 4th week and 6th week after the beginning of the trial).
Conducted on affected finger or toes every other week for four sessions.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Scoring system for paronychia related to oncologic treatments (SPOT)
Time Frame: Evaluated at baseline
The SPOT evaluates severity of each hand or foot based on four parameters, including redness, edema, discharge and granulation tissue, each measured on a 4-point scale from 0 to 3 with 0 for no presence of signs and 3 for most severe of lesions. In each parameter, the finger (or toe) with the highest score was selected to be representative of the hand (or foot), and the sum of the four parameters makes the total score of the hand or foot. The highest score of each parameter could originate from different fingers (or toes). The total score of each hand (or foot) ranges from 0 to 12.
Evaluated at baseline
Scoring system for paronychia related to oncologic treatments (SPOT)
Time Frame: Evaluated at week 2 after the initiation of intervention
The SPOT evaluates severity of each hand or foot based on four parameters, including redness, edema, discharge and granulation tissue, each measured on a 4-point scale from 0 to 3 with 0 for no presence of signs and 3 for most severe of lesions. In each parameter, the finger (or toe) with the highest score was selected to be representative of the hand (or foot), and the sum of the four parameters makes the total score of the hand or foot. The highest score of each parameter could originate from different fingers (or toes). The total score of each hand (or foot) ranges from 0 to 12.
Evaluated at week 2 after the initiation of intervention
Scoring system for paronychia related to oncologic treatments (SPOT)
Time Frame: Evaluated at week 4 after the initiation of intervention
The SPOT evaluates severity of each hand or foot based on four parameters, including redness, edema, discharge and granulation tissue, each measured on a 4-point scale from 0 to 3 with 0 for no presence of signs and 3 for most severe of lesions. In each parameter, the finger (or toe) with the highest score was selected to be representative of the hand (or foot), and the sum of the four parameters makes the total score of the hand or foot. The highest score of each parameter could originate from different fingers (or toes). The total score of each hand (or foot) ranges from 0 to 12.
Evaluated at week 4 after the initiation of intervention
Scoring system for paronychia related to oncologic treatments (SPOT)
Time Frame: Evaluated at week 6 after the initiation of intervention
The SPOT evaluates severity of each hand or foot based on four parameters, including redness, edema, discharge and granulation tissue, each measured on a 4-point scale from 0 to 3 with 0 for no presence of signs and 3 for most severe of lesions. In each parameter, the finger (or toe) with the highest score was selected to be representative of the hand (or foot), and the sum of the four parameters makes the total score of the hand or foot. The highest score of each parameter could originate from different fingers (or toes). The total score of each hand (or foot) ranges from 0 to 12.
Evaluated at week 6 after the initiation of intervention
Scoring system for paronychia related to oncologic treatments (SPOT)
Time Frame: Evaluated at week 8 after the initiation of intervention
The SPOT evaluates severity of each hand or foot based on four parameters, including redness, edema, discharge and granulation tissue, each measured on a 4-point scale from 0 to 3 with 0 for no presence of signs and 3 for most severe of lesions. In each parameter, the finger (or toe) with the highest score was selected to be representative of the hand (or foot), and the sum of the four parameters makes the total score of the hand or foot. The highest score of each parameter could originate from different fingers (or toes). The total score of each hand (or foot) ranges from 0 to 12.
Evaluated at week 8 after the initiation of intervention

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Pain visual analogue scale
Time Frame: Evaluated at baseline, week 2, 4, 6 and 8 after the initiation of intervention
Patients rate their severity of pain on a scale of 0 to 10, with 0 for no pain, 5 for moderate pain, and 10 for the worst pain ever experienced.
Evaluated at baseline, week 2, 4, 6 and 8 after the initiation of intervention
Physician global assessment
Time Frame: Evaluated at week 2, 4, 6 and 8 after the initiation of intervention

The physician rates the improvement of lesions based on digital photographs on a scale of 0 to 6, representing:

0, total clearance (100% improvement);

  1. almost total clearance (90% improvement);
  2. distinct clearance (75% improvement);
  3. moderate clearance (50% improvement);
  4. mild clearance (25% improvement);
  5. no change;
  6. worse.
Evaluated at week 2, 4, 6 and 8 after the initiation of intervention
Patient global assessment
Time Frame: Evaluated at week 2, 4, 6 and 8 after the initiation of intervention
Patients rate their extent of improvement of lesions on a scale of 0 to 10, with 0 for no improvement, 5 for moderate improvement, and 10 for total clearance of lesions.
Evaluated at week 2, 4, 6 and 8 after the initiation of intervention

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

December 21, 2021

Primary Completion (Actual)

January 21, 2023

Study Completion (Actual)

March 21, 2023

Study Registration Dates

First Submitted

November 10, 2021

First Submitted That Met QC Criteria

December 19, 2021

First Posted (Actual)

December 21, 2021

Study Record Updates

Last Update Posted (Estimate)

May 4, 2023

Last Update Submitted That Met QC Criteria

May 1, 2023

Last Verified

May 1, 2023

More Information

Terms related to this study

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

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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