Pilot Study to Compare Topical Voriconazole to Placebo as a Pain Reducing Agent

NCT02689713 | Withdrawn Phase 2 FDA Drug

• 1 other identifier: HSC20120196H
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

This study seeks to test if the study drug (voriconazole), when applied topically to a burn wound on the skin will help to reduce pain.

Conditions

Pain; Thermal Injury; Burns; Hyperalgesia

Keywords

Burn Pain; Hyperalgesia; TRPV1; OLAMs

Outcome Measures

Primary Outcomes (4)

• Pain Levels reported by patient on the Four Point Category Pain Scale at specific timepoints over 72 hours will be compared to pre-operative baseline pain report.

  Subjects will complete a pre-op pain assessment tool (Four Point Category Pain Scale consisting of 0-3 numeric with corresponding adjectives), then complete the same instrument at 1, 3, 6, 9, 12, 24, 36,48, 60 and 72 hours post-procedure.

  Pre-operatively then over 72 hours post-skin graft procedure (1, 3, 6, 9, 12, 24, 36,48, 60 and 72 hours)

• Pain Levels reported by the patient on the Heft-Parker Pain Scale at specific timepoints over 72 hours will be compared to pre-operative baseline pain report.

  Subjects will complete a pre-op pain assessment tool (Heft-Parker Pain Scale - 170mm), then complete the same instrument at 1, 3, 6, 9, 12, 24, 36,48, 60 and 72 hours post-procedure.

  Pre-operatively then over 72 hours post-skin graft (1, 3, 6, 9, 12, 24, 36,48, 60 and 72 hours)

• Pain Levels reported by the patient on the Visual Analog Pain Scale at specific timepoints over 72 hours compared to pre-operative baseline pain report.

  Subjects will complete a pre-op pain assessment tool (Visual Analog Pain Scale - 100mm), then complete the same instrument at 1, 3, 6, 9, 12, 24, 36,48, 60 and 72 hours post-procedure.

  Pre-operatively then over 72 hours post-skin graft (1, 3, 6, 9, 12, 24, 36,48, 60 and 72 hours)

• Cutaneous dialysate levels collected over time to measure baseline vs. timepoint oxidized linoleic acid metabolites (OLAMs) levels.

  Microdialysates will be collected from the CMA-70 probe and CMA-106 pump at 1, 2, 3, 6, 9,12, 24, 36, 48,60, and 72 hours post drug administration \[+/- 20 minutes per time interval\]. The specific timepoint dialysates levels will be analysed and compared to baseline.

  Over 72 hours post-skin graft (1, 3, 6, 9, 12, 24, 36,48, 60 and 72 hours)

Secondary Outcomes (1)

• Skin graft donor site wounds compared for cosmetic healing via photograph at post-op visit

  At scheduled post-op visit between 30-45 days post-procedure

Study Arms (2)

Topical Voriconazole Study Drug Group

EXPERIMENTAL

Subjects between 18 and 60 years old who have sustained a burn wound of less than 30% total body surface area, or traumatic wounds requiring skin graft will have the Topical Voriconazole study drug placed on graft site.

Drug: Voriconazole (topical)

Topical Sterile Water Placebo Group

PLACEBO COMPARATOR

Subjects between 18 and 60 years old who have sustained a burn wound of less than 30% total body surface area, or traumatic wounds requiring skin graft will have the Topical Sterile Water Placebo placed on graft site.

Drug: Topical Sterile Water Placebo Group

Interventions

Voriconazole (topical) DRUG

The voriconazole (Vfend®-IV 200mg) will be applied topically to one of two skin graft sites at a concentration of 150 micromolar. Dialysates will be collected over 12 hours post-skin graft/voriconazole application for analysis in the lab of OLAM concentrations.

Also known as: Vfend IV 200mg

Topical Voriconazole Study Drug Group

Topical Sterile Water Placebo Group DRUG

Sterile water will be applied topically to the other of the two skin graft sites. Dialysates will be collected over 12 hours post-skin graft/sterile water application for analysis in the lab of OLAM concentrations.

Also known as: Sterile Water Placebo

Topical Sterile Water Placebo Group

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Subject must be at least 18 years of age and no older than 60 years of age of either gender and in good general health.
• Subject has sustained burn wounds of less than 30 percent of the total body surface area, in order to minimize the systemic effects on wound healing and the risk of infection (both of which increase with increasing burn size).
• Subject has sustained Burn or trauma/orthopedic wounds do not involve the harvesting area.
• Subject has sustained burn or trauma/orthopedic wounds that, in the judgment of the attending surgeon, require excision and grafting of sufficient extent to justify two donor sites of equal and symmetrical size on non-dependent body surfaces areas. Note: Only two donor sites will be studied, however if the subject requires more than two donor sites, they will not be excluded.
• The scheduled excision and grafting procedure is the first such operation for the subject during this hospitalization and injury.
• Subject agrees to participate in follow-up evaluations (Post Op Day 0-3 and one follow up appointment between Post Op day 30-45 for Donor site evaluation and photos of both donor sites.

You may not qualify if:

• Critical illnesses such as those requiring ventilator support, or having a systemic infection or hemodynamic instability, defined as a mean arterial pressure less than 60 for an extended period of time or requiring vasoactive medications to support blood pressure.
• Patients unable to accurately communicate pain secondary to medical illness, altered mental status, spinal cord injury, and known current narcotic drug use.
• Patients unable to make his/her own decision for the informed consent. (Not seeking consent from the legal authorized representative; self consent only).
• Major acute or chronic medical illnesses that could affect wound healing (e.g. peripheral vascular disease, blood clotting disorder).
• Cellulitis or other infection of the potential donor sites.
• Donor site has been previously harvested for grafting.
• Donor site crosses a joint.
• Any Corticosteroid use that could interfere with wound healing thus OLAM levels.
• Subjects with greater than 30% total body surface area burns.
• Pregnancy or lactation. (Beta HCG pregnancy test completed prior to operative procedure, not part of study) In the event that we have a record of a hysterectomy, no pregnancy test will be done, and the subject will be assumed NOT to be pregnant.
• Prisoners.
• Subjects having any contraindications for voriconazole. The contraindications are 1) known hypersensitivity to voriconazole; and 2) Coadministration of terfenadine, astemizole, cisapride, pimozide, quinidine or sirolimus, rifampin, carbamazepine, long acting barbiturates, high dose ritonavir, rifabutin, ergotamine, dihydroergotamine, oral contraceptives or St. John's Wort. A one week washout shall be determined for the above listed medications prior to allowing entry into the study.

Sponsors & Collaborators

• Kenneth Hargreaves: lead
• San Antonio Military Medical Center: collaborator
• U.S. Army Medical Research and Development Command: collaborator

Study Sites (1)

San Antonio Military Medical Center

San Antonio, Texas, 78234, United States

Location

MeSH Terms

Conditions

Pain; Burns; Hyperalgesia

Interventions

Voriconazole

Condition Hierarchy (Ancestors)

Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Wounds and Injuries; Somatosensory Disorders; Sensation Disorders; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Christopher E White, MD

  Brook Army Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: SUPPORTIVE CARE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Chair, Dept. of Endodontics

Study Record Dates

• First Submitted: February 4, 2016
• First Posted: February 24, 2016
• Study Start: June 15, 2018
• Primary Completion: November 14, 2018
• Study Completion: November 14, 2018
• Last Updated: December 17, 2018

Record last verified: 2018-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)