Intralesional Injection of Combined Digoxin and Furosemide Versus 5-Flurouracil in Plantar Warts

Sponsor

Zagazig University (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05599971

Collaborator

(none)

Enrollment

Arms

Anticipated Duration (Months)

Study Details

Study Description

Brief Summary

The aim of the current work is to evaluate the efficacy and safety of intralesional combined Digoxin and furosemide versus intralesional 5-flurouracil in the treatment of plantar warts.

Condition or Disease	Intervention/Treatment	Phase
Plantar Wart	Drug: intralesional combined digoxin and furosemide Drug: intralesional injection of 5- Fluorouracil Other: intralesional saline	N/A

Detailed Description

Warts are benign proliferations of skin and mucosa caused by the human papilloma virus (HPV). Currently, over 170 HPV types have been identified. Certain HPV types tend to infect skin at specific anatomical sites, such as palmoplantar warts, which are typically caused by serotypes 1, 2, and 4, however warts caused by any HPV type can occur at any site (Tulay & Serakinci, 2016).

Plantar warts most commonly present with pain that occur with activities that put pressure on the soles of the feet. They commonly affect plantar areas of increased pressure, such as the heels or metatarsal heads. On gross inspection, plantar warts may appear as a singular rough, flesh-colored to yellow or grey-brown, hyperkeratotic papule, or a thickened "cobblestoned" plaque, termed a mosaic wart, which consists of multiple plantar warts that have coalesced (Witchey et al., 2018).

There are several modalities for the treatment of warts including, cryotherapy, electrocoagulation, topical salicylic acid, topical 5-fluorouracil, intralesional immunotherapy, and laser surgery. All these treatment options can be painful, time-consuming, and/or expensive, and none is considered the gold standard (Latif et al., 2021).

K+ influx is essential for the replication of DNA viruses, such as HPV. Both digoxin, which is a cardiac glycoside, and furosemide, which is a loop diuretic, inhibit the K+ influx by interacting with cell membrane ion co-transporters (Na+/K+-ATPase and Na+-K+-2Cl-co-transporter-1). Therefore, it is hypothesized that these two compounds may be valuable in the treatment of HPV-induced warts. This new approach is called ionic contra-viral therapy (Rijsbergen et al., 2019). Intralesional injection of combined digoxin and furosemide was found to be safe and effective as a treatment option for multiple plantar warts (Fathy et al., 2021).

5-Fluorouracil (5-FU) is an antimetabolite that can be used alone or with other chemotherapeutic agents to treat solid tumors. It is one of the pyrimidine analogues. Due to its structure, 5-FU disrupts nucleoside metabolism and can be integrated into the single and double helix of RNA and DNA, respectively, causing cell cytotoxicity and death (Zoheir et al., 2022).

Intralesional 5-fluorouarcil has been found to be a highly effective, safe and cheap alternative in the treatment of warts, with a significantly good response in genital warts also (Kamal et al., 2108).

Study Design

Study Type:

Interventional

Anticipated Enrollment :

45 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Single (Participant)

Primary Purpose:

Treatment

Official Title:

The Efficacy of Intralesional Injection of Combined Digoxin and Furosemide Versus 5-Flurouracil in the Treatment of Plantar Warts

Anticipated Study Start Date :

Nov 1, 2022

Anticipated Primary Completion Date :

Nov 1, 2023

Anticipated Study Completion Date :

Feb 1, 2024

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Group A 15 patients will receive intralesional 0.1 mL of combined digoxin and furosemide, with maximum 5 warts per session.	Drug: intralesional combined digoxin and furosemide 15 patients will receive intralesional combined digoxin and furosemide, with maximum 5 warts per session. 0.2 mL of lignocaine (20 mg/mL) will be used as a local analgesic and after few minutes, 0.1 mL of combined digoxin and furosemide solution will be slowly injected into the base of each wart. Selected patients will receive one session every 2 weeks till complete clearance or up to 5 sessions.
Active Comparator: Group B 15 patients will receive intralesional injection of 5- Fluorouracil (50mg/ml) in full concentration into the wart using a 27- gauge insulin syringe till the entire lesion begins to puff up. The maximum dose injected per session will be 2ml of 5-FU.	Drug: intralesional injection of 5- Fluorouracil 15 patients will receive intralesional injection of 5- Fluorouracil (50mg/ml) in full concentration into the wart using a 27- gauge insulin syringe till the entire lesion begins to puff up. The maximum dose injected per session will be 2ml of 5-FU. Selected patients will receive one session every 2 weeks till complete clearance or up to 5 sessions.
Placebo Comparator: Group c 15 patients will receive intralesional saline.	Other: intralesional saline 15 patients will receive intralesional saline. Selected patients will receive one session every 2 weeks till complete clearance or up to 5 sessions.

Arm

Intervention/Treatment

Active Comparator: Group A

15 patients will receive intralesional 0.1 mL of combined digoxin and furosemide, with maximum 5 warts per session.

Drug: intralesional combined digoxin and furosemide

15 patients will receive intralesional combined digoxin and furosemide, with maximum 5 warts per session. 0.2 mL of lignocaine (20 mg/mL) will be used as a local analgesic and after few minutes, 0.1 mL of combined digoxin and furosemide solution will be slowly injected into the base of each wart. Selected patients will receive one session every 2 weeks till complete clearance or up to 5 sessions.

Active Comparator: Group B

15 patients will receive intralesional injection of 5- Fluorouracil (50mg/ml) in full concentration into the wart using a 27- gauge insulin syringe till the entire lesion begins to puff up. The maximum dose injected per session will be 2ml of 5-FU.

Drug: intralesional injection of 5- Fluorouracil

Placebo Comparator: Group c

15 patients will receive intralesional saline.

Other: intralesional saline

15 patients will receive intralesional saline. Selected patients will receive one session every 2 weeks till complete clearance or up to 5 sessions.

Outcome Measures

Primary Outcome Measures

change in size of the warts [through study completion, an average of 9 months]
The studied warts will be clinically evaluated regarding change in size
Dermoscopic evaluation [through study completion, an average of 9 months]
The patients will be categorized in to 4 scores according to their response to treatment as: Score 0: patients showed neither clinical response nor dermoscopic clearance of warts 2 weeks after the last treatment session. Score 1: patients showed clinical improvement with decreased size of wart and thickness of callus without dermoscopic clearance of warts 2 weeks after the last treatment session. Score 2: patients showed disappearance of warts clinically (clinical clearance) but dermoscopic examination revealed remnants of warts 2 weeks after the last treatment session. Score 3: patients showed clinical and dermoscopic clearance of warts 2 weeks after the last treatment session (Barkat et al., 2018).
treatment-related adverse effects [through study completion, an average of 9 months]
Immediate and late adverse effects will be evaluated
Patients' satisfaction [through study completion, an average of 9 months]
Patients' satisfaction will be evaluated through a questionnaire. Patients' satisfaction will be graded into (very satisfied, satisfied, and unsatisfied).

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Patients with multiple plantar warts (≥ 3) will be included.

Exclusion Criteria:

Patients under 18 years old or patients over 65 years old.
Pregnancy or breast feeding.
Patients received vaccination or any other treatment of warts during the last month.
Patients with a known sensitivity to any of the investigational product ingredients.
Patients with history of asthma, allergic skin disorders or convulsions.
Patients with signs of any systemic or local inflammation or infection.
Patients with any evidence of immunosuppression including HIV.
History of cardiac diseases, relevant abnormal K level or ECG abnormalities for patients who will receive the combined digoxin and furosemide.

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

Zagazig University

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

Publications

None provided.

Responsible Party:

Norhan Anees, Principal Investigator, Zagazig University

ClinicalTrials.gov Identifier:

NCT05599971

Other Study ID Numbers:

planter wart treatment

First Posted:

Oct 31, 2022

Last Update Posted:

Oct 31, 2022

Last Verified:

Oct 1, 2022

Studies a U.S. FDA-regulated Drug Product:

Studies a U.S. FDA-regulated Device Product:

Additional relevant MeSH terms:

Study Results

No Results Posted as of Oct 31, 2022