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

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ClinicalTrials.gov Identifier: NCT02689713
Recruitment Status : Recruiting
First Posted : February 24, 2016
Last Update Posted : June 21, 2018
Sponsor:
Collaborators:
San Antonio Military Medical Center
U.S. Army Medical Research and Materiel Command
Information provided by (Responsible Party):
Kenneth Hargreaves, The University of Texas Health Science Center at San Antonio

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.

Condition or disease Intervention/treatment Phase
Pain Thermal Injury Burns Hyperalgesia Drug: Voriconazole (topical) Drug: Topical Sterile Water Placebo Group Phase 2

Detailed Description:
This single-center, prospective, randomized, double-blind, controlled pilot study conducted at San Antonio Military Medical Center will evaluate the effectiveness of topical voriconazole for pain relief at autogenous skin donor sites compared to a topical placebo application. The patients will act as their own control. All participants and investigators in the study will be blinded to the treatment arm utilized on each of the patient's donor sites (voriconazole versus placebo). Patients, who are scheduled for skin grafting and have met the inclusion criteria for this study, will be invited to enroll in the study. Only those patients who have been planned for skin graft sites that are approximately symmetrical in size will be allowed to enroll in the study. The donor site wounds will be studied using a paired design consisting of voriconazole or the placebo applied topically to same-patient matched donor sites. Patients will be queried via the pain assessment tool as to perceived pain at timed intervals. Dialysate samples will be collected via microdialysis probes at matching timed intervals in order to measure levels of oxidized linoleic acid metabolites shown in previous studies to be present in peripheral nerves.

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 100 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Supportive Care
Official Title: Prospective, Randomized, Double-blind Controlled Pilot Study to Compare Topical Voriconazole to Placebo as a Pain Reducing Agent at Skin Donor Sites
Actual Study Start Date : June 15, 2018
Estimated Primary Completion Date : June 2020
Estimated Study Completion Date : June 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Topical Voriconazole Study Drug Group
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)
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.
Other Name: Vfend IV 200mg

Placebo Comparator: Topical Sterile Water Placebo Group
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
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.
Other Name: Sterile Water Placebo




Primary Outcome Measures :
  1. 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. [ Time Frame: Pre-operatively then over 72 hours post-skin graft procedure (1, 3, 6, 9, 12, 24, 36,48, 60 and 72 hours) ]
    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.

  2. 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. [ Time Frame: Pre-operatively then over 72 hours post-skin graft (1, 3, 6, 9, 12, 24, 36,48, 60 and 72 hours) ]
    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.

  3. 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. [ Time Frame: Pre-operatively then over 72 hours post-skin graft (1, 3, 6, 9, 12, 24, 36,48, 60 and 72 hours) ]
    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.

  4. Cutaneous dialysate levels collected over time to measure baseline vs. timepoint oxidized linoleic acid metabolites (OLAMs) levels. [ Time Frame: Over 72 hours post-skin graft (1, 3, 6, 9, 12, 24, 36,48, 60 and 72 hours) ]
    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.


Secondary Outcome Measures :
  1. Skin graft donor site wounds compared for cosmetic healing via photograph at post-op visit [ Time Frame: At scheduled post-op visit between 30-45 days post-procedure ]
    Digital photographs of the wounds will be taken at the post-op visit scheduled between 30-45 days after the skin graft procedure to assess the cosmetic appearance of the two wound sites.



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Ages Eligible for Study:   18 Years to 60 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

1.1 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.

1.2 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).

1.3 Subject has sustained Burn or trauma/orthopedic wounds do not involve the harvesting area.

1.4 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.

1.5 The scheduled excision and grafting procedure is the first such operation for the subject during this hospitalization and injury.

1.6 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.

Exclusion Criteria:

2.1 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.

2.2 Patients unable to accurately communicate pain secondary to medical illness, altered mental status, spinal cord injury, and known current narcotic drug use.

2.3 Patients unable to make his/her own decision for the informed consent. (Not seeking consent from the legal authorized representative; self consent only).

2.4 Major acute or chronic medical illnesses that could affect wound healing (e.g. peripheral vascular disease, blood clotting disorder).

2.6 Cellulitis or other infection of the potential donor sites.

2.7 Donor site has been previously harvested for grafting.

2.8 Donor site crosses a joint.

2.9 Any Corticosteroid use that could interfere with wound healing thus OLAM levels.

2.10 Subjects with greater than 30% total body surface area burns.

2.11 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.

2.12 Prisoners.

2.13 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.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02689713


Contacts
Contact: Kenneth M Hargreaves, DDS, Phd 210-567-0895 hargreaves@uthscsa.edu
Contact: Erin Locke, RN, BSN 210-567-0895 locke@uthscsa.edu

Locations
United States, Texas
San Antonio Military Medical Center Recruiting
San Antonio, Texas, United States, 78234
Contact: Christopher White, MD       christopher.e.white34.mil@mail.mil   
Sponsors and Collaborators
Kenneth Hargreaves
San Antonio Military Medical Center
U.S. Army Medical Research and Materiel Command
Investigators
Principal Investigator: Christopher E White, MD Brook Army Medical Center

Responsible Party: Kenneth Hargreaves, Chair, Dept. of Endodontics, The University of Texas Health Science Center at San Antonio
ClinicalTrials.gov Identifier: NCT02689713     History of Changes
Other Study ID Numbers: HSC20120196H
First Posted: February 24, 2016    Key Record Dates
Last Update Posted: June 21, 2018
Last Verified: June 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: No plan to share data.

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Kenneth Hargreaves, The University of Texas Health Science Center at San Antonio:
Burn Pain
Hyperalgesia
TRPV1
OLAMs

Additional relevant MeSH terms:
Hyperalgesia
Somatosensory Disorders
Sensation Disorders
Neurologic Manifestations
Nervous System Diseases
Signs and Symptoms
Voriconazole
Antifungal Agents
Anti-Infective Agents
14-alpha Demethylase Inhibitors
Cytochrome P-450 Enzyme Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Steroid Synthesis Inhibitors
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Cytochrome P-450 CYP3A Inhibitors