Efficacy and Safety of Topical Timolol in Secondary Intention Surgical Wounds Healing

Official title

Efficacy and Safety of Topical Timolol in the Treatment of Cutaneous Surgical Wounds Left to Heal by Secondary Intention

Overview

The purpose of this research study is to evaluate the efficacy and safety of topical timolol 0.5% for secondary intention wound healing following 1) Mohs micrographic surgery, 2) standard surgical excision, OR 3) electrodesiccation and curettage (ED\&C). Please note that healing by secondary intention refers to when a wound heals naturally without surgical closure. To evaluate the efficacy of topical timolol 0.5%, 220 participants will be recruited. Participants will be placed into one of two groups: The treatment group or the control group. 1. The treatment group will receive a topical timolol 0.5% solution, which will be applied to their wound daily for 12 weeks. 2. The control group will receive standard care with the addition of hydrogel, which will also be applied to their wound daily for 12 weeks. During this 12-week period, both groups will be required to upload photos of their wound healing to their MyChart account at weeks 3, 6, 9, and 12. These photos will be reviewed by the investigator to assess wound healing. Re-epithelialization and earlier complete wound healing will be compared between both groups to determine the efficacy of topical timolol 0.5% solution compared to the standard of care.

Detailed description

Secondary intention healing after cutaneous excisions or Mohs surgery is a commonly utilized technique in areas that are under high tension, in which primary closure would not be effective, or when patients defer a more complex closure technique. Secondary intention healing has drawbacks, as they take longer to heal and patients are left with a large wound at the surgical site for approximately 8 weeks. Topical timolol has shown promising results in lower extremity ulcers to improve wound healing, however larger trials on secondary intention surgical wounds have not been studied. This trial aims to fill this gap by comparing the efficacy and safety of topical timolol to standard wound care over a 12-week interval.

Participants who agree to the study, and who have opted to heal by secondary intention healing following their 1) Mohs micrographic surgery, 2) standard surgical excision, OR 3) electrodesiccation and curettage (ED\&C) will be consented.

Once consented, the participant's demographics, medical history, and surgery details will be collected before being randomized into one of two groups: the treatment group or the control group.

1. The treatment group will receive a topical timolol 0.5% solution, which will be applied to their wound daily for 12 weeks. 2. The control group will receive standard care with the addition of hydrogel, which will also be applied to their wound daily for 12 weeks.

The participants and the research team will be blinded, meaning that they will not know which treatment the participant receives. Participants in both groups will be asked to upload photos of their wound healing at weeks 3, 6, 9, and 12 for the research team to examine.

The data will be analyzed to determine which group experienced faster re-epithelialization and earlier complete wound healing.

Interventions

• Drug Timolol 0.5% Ophthalmic Solution
  Topical Timolol 0.5% solution will be applied to patients wounds in 2 cm intervals along the widest diameter of the wound daily for 12 weeks following their medical procedure.
• Other Hydrogel of placebo
  Hydrogel will be placed on the wound at 2 cm intervals along the widest diameter of the wound daily for 12 weeks following the patient's medical procedure.

Primary outcome measures

• Area of Surgical Ulcer [Time frame: Baseline, week 3, week 6, week 9 and week 12]

Secondary outcome measures (8)

• Infection Rate [Time frame: Baseline to Week 12]
• Risk Factor for Poor Wound Healing [Time frame: Baseline to Week 12]
• Type of Wounds [Time frame: Baseline to Week 12]
• Incidences of Hypotension [Time frame: Baseline to Week 12]
• Incidences of COPD or Asthma Exacerbations [Time frame: Baseline to Week 12]
• Incidences of Hypertrophic Scar or Keloid [Time frame: Baseline to Week 12]
• Incidences of Post Operative Bleeding [Time frame: Baseline to Week 12]
• Use of Antibiotic [Time frame: Baseline to Week 12]

Eligibility criteria

Inclusion criteria

• Male or female subject of any race 18 years old or older
• Patient opt to heal by secondary intention healing after discussion of reconstructive options following excision
• Patients undergoing Mohs micrographic surgery, standard surgical excision, or electrodesiccation and curettage (ED\&C) whose wounds are managed by secondary intention healing.
• Willing to send photos of ulcer at 3 week intervals with ruler measuring length by width
• Able to give informed consent themselves

Exclusion criteria

• Cyst excisions (due to concern for inflammation)
• Site shows evidence of infection (defined as a moderate or severe rating of all of the following clinical signs/symptoms: 1) increased warmth, 2) increased pain, 3) erythema, and 4) malodorous exudate at Screening or at Randomization (Visit 1), OR total organism count > 1 x 105 colony forming units (CFU) from the screening visit study ulcer culture sample)
• Severe COPD/asthma/cardiac arrhythmia
• Hx of documented beta blocker allergy
• Cognitive impairment
• Has medically documented history of Human Immunodeficiency Virus (HIV)
• Has active malignancy on the study limb
• Has immunodeficiency as defined by serum IgG, IgA, and IgM less than one-half the lower limit of normal
• Has severe protein malnutrition as defined by serum albumin < 2.5 g/dL
• Has serum aspartate aminotransferase (AST, SGOT, GOT) or serum alanine aminotransferase (ALT, SGPT, GPT) levels greater than twice the upper limit of normal
• Has fatigue, palpitations, dyspnea, and/or angina at rest
• Has a medically documented or self-reported history, within the previous 12 months from date of Screening Visit, of alcohol or drug abuse, particularly methadone or heroin
• Has received previous treatment with the following during the 60 days prior to Screening: Immunosuppressive agents, radiation, chemotherapy, growth factors (epidermal growth factor, tumor necrosis factor, transforming growth factor, platelet derived growth factor, etc.)
• Has received previous treatment with the following during the 30 days prior to screening: the site of the study ulcer, split- or full-thickness skin graft at the site of the study ulcer, biologically-active (or engineered) cellular or acellular product(s) at the site of the study ulcer, investigational drug or device
• Has history of bradycardia (heart rate less than 60)
• Has ESR>70mm/hr and CRP>100 mg/L at time of screening
• Has medically documented history of hypotension/orthostatic hypotension and/or symptomatic hypotension (systolic blood pressure below 90 and diastolic blood pressure less than 60). (Note: There is no standard testing regimen protocol for orthostatic hypotension, even for patients starting on oral timolol)
• Currently taking asthma or COPD medications (as documented in chart)
• Has a medically documented diagnosis of myasthenia gravis, untreated hyperthyroidism, , Type 2, Type 3 heart block, cardiogenic shock, overt cardiac failure
• Female who is pregnant or refuses to use adequate contraceptive methods and is of childbearing age during the trial
• Prisoners, institutionalized individuals or vulnerable population

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Double blind

Primary purpose

Treatment

Study locations

United States · 2 centers

• VA Medical Center- Sacramento — Sacramento
• UC Davis Health- Dermatology — Sacramento

Identifiers

NCT: NCT07384767 · 2403423

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗