A Randomized, Placebo Controlled, Double-Blind, Single Dose Study To Evaluate The Safety And Tolerability Of Cream In Burn Patients With Induced Dermal Incisions
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 50
- 试验地点
- 2
- 主要终点
- Assessment of efficacy by performing qPCR of the fibrotic molecules at day 27 (after completion of Nefopam cream application).
研究概览
简要总结
Burn patients very commonly develop abnormal scars after injury which can be red, raised or elevated, painful and very itchy. They can prevent normal movement of hands and other joints and lead to ugly deformities which makes physical and psychological recovery very difficult. This proposal seeks to test the usefulness of a cream called Nefopam to prevent and treat these bad scars after burns and other injury to the skin. Nefopam is a drug that has been used as a pain medicine in Europe but has been found to have anti-scarring properties in rats and pigs. It has been tested in healthy people and found to be well tolerated and safe. The study purposes to make a scratch in the hip skin in 60 adult burn patients at two burn unit sites, the University of Alberta and the University of California at Davis, Sacramento CA. Burn patients in the study will have a scratch wound in the skin of the each side of the hip, part way through the thickness of the skin which is shallow at first but gets deeper. This scratch is made with a special guide which precisely controls the length and depth of the scratch so that each scratch is the same. Part of the scratch heals without scar and the deeper part heals with a red raised scar over a small region less than 2 inches long. One side will be treated with the drug and the other with a control or placebo are in a white cream that is indistinguishable, where you cannot tell which side contains the drug. Once the wound is nearly healed, usually less than 21 days, the cream will be applied twice daily for three weeks. Measurements will be done about once per month for four months where the healing scratches will be photographed, measurements of the thickness made with ultrasound and mexameter for scar color or pigment and redness. Ultrasound is a painless probe that uses sound waves to measure scar thickness and mexameter is a painless probe on the surface of the scratch to measure color and redness. Both measurements take only minutes to complete. Patients will be asked to answer a scar assessment form about on how they feel each scratch during the treatment and the research staff will also the complete scar form as well. It is the aim of the study to find a cream the works to prevent and reduce scarring after burn injury in military or civilian patients. In the future, an useful cream for scarring in burn patients may also be helpful for other skin damage which leads to scarring.
详细描述
Background:
Fibroproliferative disorders (FPD) are common and serious disorders involving many human tissues and are a leading cause of mortality and reported as high a 45% of annual deaths. Hypertrophic scar (HTS) and keloids are the dermal equivalent of FPD and impose lower mortality but great morbidity, particularly following burn injury. In the US, 1.25 million people are treated for burns annually, 50,000 requiring hospitalization. Although the mortality rate for burn injury has improved, burn patients experience a prolonged hospitalization (mean 26.2 days) and rehabilitation, requiring an average of 12.7 weeks off work for patients with thermal injuries >30% of the TBSA. Much of the rehabilitation relates to functional and cosmetic limitations imposed by HTS, including a reduction in range of motion of the extremities and the intense pruritus and heat intolerance making early return to work prohibitive, until remodelling of the HTS has occurred. Although risk factors for HTS include sex, age, racial or genetic factors, and wound location, HTS develops after prolonged inflammation of slowly healing burn wounds with a very high frequency especially in deep dermal wounds independent of other factors in up to 75% of burn patients. Unfortunately, HTS and keloid are known to respond poorly to current forms of therapy, including pressure garments, topically applied silicone and intralesional steroids, usually slowly over months or years, often incompletely. Advances in the immunology of FPD including HTS and keloids, reveal many common features, such that novel advances in therapy for these disorders may provide far reaching benefits to many patients and military personnel suffering from severe scarring after burn injury.
Drug Information: NEFOPAM HCL has been found safe and effective for the reduction of dermal scarring following standardized human dermal wounds of critical depth that produces HTS in normal human volunteers. NEFOPAM HCl was first developed as a non-narcotic analgesic drug and it is currently marketed primarily in Europe, New Zealand and parts of Asia for oral, intramuscular or intravenous use for acute or chronic pain. NEFOPAM HCl has over 30 years of human safety data. It is considered generally safe with mild side effects including nausea, sweating, dry mouth and tachycardia. NEFOPAM reformulated into a cream and topically administered has been shown to reduce the amount of scar tissue formed during wound healing in mice and the red Duroc pig model of hypertrophic scarring. Most recently, a phase I safety and efficacy study was conducted in human volunteers using a standardized progressively deeper dermal wound (0-1.6 mm in depth over 6 cm) made with a sterile jig in each hip, where normotrophic (negative control) and HTS (positive control) develop in the superficial and deep regions of the scratch. 24 patients have been studied over 104 days where the preliminary results demonstrate that NEFOPAM cream has very few adverse side effects, low immunogenicity and encouraging antifibrotic effects on the healing wounds.
Purpose/ Hypothesis:
To re-assess the safety, local tolerability and efficacy of NEFOPAM Cream in burn patients when applied to bilateral deep dermal wounds using a standardized dermal scratch model of hypertrophic scarring.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
As this is a 2 arm study. One is experimental drug and other is placebo control. No one will know which side of body part having drug and/or placebo. If required, it will be find out but this study is designed as a double blind.
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female burn, or trauma patients aged >18 - <65 years with 5-70% TBSA deep second or third degree burns who have uninjured skin in both the lateral hip regions and have voluntarily signed the Informed Consent Form (ICF).
- •Subjects with clinically acceptable results at screening for the laboratory tests specified in the trial protocol.
- •Women of childbearing potential must provide a negative pregnancy serum/urine test at time of screening and have to be compliant with an effective form of birth control throughout the entire study. Non-childbearing potential means subjects have had a history of tubal ligation or a hysterectomy or are post-menopausal with no menses for at least 1 year prior to enrolment in the study.
- •Subjects, who are, in the opinion of the Investigator, able to understand the study, co-operate with the study procedures and are willing to return to the clinic for all of the required follow-up visits.
- •Subjects must be able to cooperate with requirements of the study (e.g. able to speak, read and write English, and will be expected to be available for adverse event monitoring for the duration of the study).
- •Healthy subjects must have ALT and AST < 2 × ULN and TB < ULN at entry.
- •Subjects with carcinoma in situ or stage 1 cancer of the skin and other tissues will be acceptable once acceptable clinical management of the carcinoma has been established.
- •Patients who have well controlled HIV as defined by a viral load amount of HIV in the blood that is undetectable i.e. a: viral load less than 40 to 50 copies/ml and cannot be detected by standard tests for HIV, Hep B or Hep C will be included after consultation with an infectious disease expert.
排除标准
- •Currently Subjects involved any other intervention trial(s) where the intervention could possibly affect wound healing to be eligible for enrolment in the SCX-001 (Nefopam) Cream study.
- •Subjects who have scarring from previous interventions or evidence of thermal, electrical or radiation burn scars, tattoos, birthmarks or moles within 5 cm of the treatment site.
- •Exclusion criteria specific to burn patients in addition to the previously described factors would include severe inhalation injury requiring FiO2 >50%, renal failure requiring dialysis or hemodynamic instability requiring vasopressor therapy at the time of initiation of therapy.
- •Subjects with a history or family history of abnormal keloid scarring.
- •Subjects with additional concurrent illnesses or conditions that may have interfered with wound healing like neoplastic, immune-mediated, or primary infectious disease (e.g. carcinoma, vasculitis, connective tissue disease, immune system disorders, rheumatoid arthritis, chronic renal impairment, significant hepatic impairment, inadequately or uncontrolled congestive heart failure or diabetes mellitus) or any clinically significant medical condition or history of any condition which may impair wound healing.
- •Subjects with a skin disorder that is chronic or currently active and which the investigator considers will adversely affect the healing of acute wounds or will involve the areas to be examined in this trial (including psoriasis, dermatitis, eczema)
- •Subjects with a body mass index <15 or >35 kg/m
- •A history of radiotherapy to the study scar area.
- •Subjects who are positive for HIV, hepatitis B or C.
- •Subjects who have known sensitivities to SCX-001 (Nefopam) Cream, structurally related compounds or any of the constituents of SCX-001 (Nefopam) Cream.
- •Subjects who have known sensitivities to EMLA cream, chlorhexidine or adhesive dressings.
- •Elder patients (> 65 years), patients with epilepsy, patients with urinary retention, or or when administered with other anticholinergic or sympathomimetic drugs or monoamine oxidase inhibitors (MAOIs) or tricyclic antidepressants.
- •Subjects with end stage renal disease, where eGFR </= 30 mL/min.
研究组 & 干预措施
Placebo
This will work as a placebo for the experimental drug.
干预措施: Placebo (Vehicle) (Other)
Nefopam
NEFOPAM 3% cream will be applied topically to healing deep dermal scratches in the lateral hip of burn patients daily (twice) for 3 weeks during the proliferative phase of wound healing.
干预措施: Nefopam (Drug)
结局指标
主要结局
Assessment of efficacy by performing qPCR of the fibrotic molecules at day 27 (after completion of Nefopam cream application).
时间窗: Two punch biopsies will be performed on the maximally thick region of each scar on Day 27 (after completion of Nefopam cream application).
To determine the efficacy of Nefopam cream versus placebo on the fibrotic molecules including type I and type III collagen, β-catenin target gene (AXIN-2), TGF- β1, and decorin, quantitative measures will be performed. TGF-β1, AXIN-2, decorin, and collagen types I and III will be expressed as fold-change values; fold change values will be calculated based on the double delta Ct method (where fold change = 2-∆∆CT).
Assessment of efficacy by measuring scar/wound area at day 21.
时间窗: Digital photography of the wound/scar will be performed at day 21.
To check the efficacy of the Nefopam cream all comparisons will be made between the Nefopam cream and the Placebo at different time point. Wound area will be measured using images obtained through digital photography on day 1 post operatively. Each image will be analyzed twice and the values averaged to provide an estimate of wound area (mm2) for each wound. Within-subject differences in wound area will be calculated and summarized by treatment group.
Assessment of efficacy by measuring scar/wound area at day 27.
时间窗: Digital photography of the wound/scar will be performed at day 27.
To check the efficacy of the Nefopam cream all comparisons will be made between the Nefopam cream and the Placebo at different time point. Wound area will be measured using images obtained through digital photography on day 1 post operatively. Each image will be analyzed twice and the values averaged to provide an estimate of wound area (mm2) for each wound. Within-subject differences in wound area will be calculated and summarized by treatment group.
Assessment of efficacy by performing Immunohistochemistry at day 104 (after completion of Nefopam cream application).
时间窗: Two punch biopsies will be performed on the maximally thick region of each scar on Day 104 (after completion of Nefopam cream application).
To determine the efficacy of Nefopam cream versus placebo, protein expression of fibrotic molecules will be measured by immunohistochemistry. a-SMA (smooth muscle actin) and β -catenin immunohistochemistry will be performed at day 104.
Assessment of efficacy by measuring scar/wound area at day 48.
时间窗: Digital photography of the wound/scar will be performed at day 48.
To check the efficacy of the Nefopam cream all comparisons will be made between the Nefopam cream and the Placebo at different time point. Wound area will be measured using images obtained through digital photography on day 1 post operatively. Each image will be analyzed twice and the values averaged to provide an estimate of wound area (mm2) for each wound. Within-subject differences in wound area will be calculated and summarized by treatment group.
Assessment of efficacy by measuring scar/wound depth at day 1.
时间窗: Dermal ultrasound analysis of the wound/scar will be performed at day 1.
To check the efficacy of the Nefopam cream all comparisons will be made between the Nefopam cream and the Placebo at different time point. At each visit there are three (3) measurements of wound depth at three (3) different points (deep end, mid-point, superficial end) will be taken. Scar depth will be measured in mm, based on ultrasound readings taken at scheduled assessment times.
Assessment of efficacy by measuring scar/wound depth at day 21.
时间窗: Dermal ultrasound analysis of the wound/scar will be performed at day 21.
To check the efficacy of the Nefopam cream all comparisons will be made between the Nefopam cream and the Placebo at different time point. At each visit there are three (3) measurements of wound depth at three (3) different points (deep end, mid-point, superficial end) will be taken. Scar depth will be measured in mm, based on ultrasound readings taken at scheduled assessment times.
Assessment of efficacy by measuring scar/wound depth at day 48.
时间窗: Dermal ultrasound analysis of the wound/scar will be performed at day 48.
To check the efficacy of the Nefopam cream all comparisons will be made between the Nefopam cream and the Placebo at different time point. At each visit there are three (3) measurements of wound depth at three (3) different points (deep end, mid-point, superficial end) will be taken. Scar depth will be measured in mm, based on ultrasound readings taken at scheduled assessment times.
Assessment of efficacy by measuring scar/wound area at day 76.
时间窗: Digital photography of the wound/scar will be performed at day 76.
To check the efficacy of the Nefopam cream all comparisons will be made between the Nefopam cream and the Placebo at different time point. Wound area will be measured using images obtained through digital photography on day 1 post operatively. Each image will be analyzed twice and the values averaged to provide an estimate of wound area (mm2) for each wound. Within-subject differences in wound area will be calculated and summarized by treatment group.
Assessment of efficacy by measuring scar/wound area at day 104.
时间窗: Digital photography of the wound/scar will be performed at day 104.
To check the efficacy of the Nefopam cream all comparisons will be made between the Nefopam cream and the Placebo at different time point. Wound area will be measured using images obtained through digital photography on day 1 post operatively. Each image will be analyzed twice and the values averaged to provide an estimate of wound area (mm2) for each wound. Within-subject differences in wound area will be calculated and summarized by treatment group.
Assessment of the scar using the Patient and Observer Scar Assessment Scales (POSAS) at day 48 (after completion of Nefopam cream application).
时间窗: Patient and Observer Scar Assessment Scales (POSAS) will be performed at day 48 (after completion of Nefopam cream application).
The POSAS consists of a section completed by the subject and sections completed by three observers - once for each hip, at each post-wound-closure visit. The Patient section consists of seven (7) questions on 10-point scales regarding scar pain, itchiness, colour, stiffness, thickness, irregularity, and an overall assessment. The Observer sections consist of seven (7) 10-point scales regarding vascularity, pigmentation, thickness, relief, pliability, surface area, and overall assessment. On Y axis POSAS scoring will be taken and on X axis outcome from the patients at different time point will be recorded. Each of the seven questions has a 10-point scoring system, with 1 representing normal skin and 10 the worst imaginable scar or sensation. The total score of both scales consists of adding the scores of each of the seven questions (range, 7 to 70). The lowest score, 7, reflects normal skin, whereas the highest score, 70, reflects the worst imaginable scar.
Assessment of the scar using the Patient and Observer Scar Assessment Scales (POSAS) at day 76 (after completion of Nefopam cream application).
时间窗: Patient and Observer Scar Assessment Scales (POSAS) will be performed at day 76 (after completion of Nefopam cream application).
The POSAS consists of a section completed by the subject and sections completed by three observers - once for each hip, at each post-wound-closure visit. The Patient section consists of seven (7) questions on 10-point scales regarding scar pain, itchiness, colour, stiffness, thickness, irregularity, and an overall assessment. The Observer sections consist of seven (7) 10-point scales regarding vascularity, pigmentation, thickness, relief, pliability, surface area, and overall assessment. On Y axis POSAS scoring will be taken and on X axis outcome from the patients at different time point will be recorded. Each of the seven questions has a 10-point scoring system, with 1 representing normal skin and 10 the worst imaginable scar or sensation. The total score of both scales consists of adding the scores of each of the seven questions (range, 7 to 70). The lowest score, 7, reflects normal skin, whereas the highest score, 70, reflects the worst imaginable scar.
Assessment of efficacy by performing qPCR of the fibrotic molecules at day 104(after completion of Nefopam cream application).
时间窗: Two punch biopsies will be performed on the maximally thick region of each scar on Day 104 (after completion of Nefopam cream application).
To determine the efficacy of Nefopam cream versus placebo on the fibrotic molecules including type I and type III collagen, β-catenin target gene (AXIN-2), TGF- β1, and decorin, quantitative measures will be performed. TGF-β1, AXIN-2, decorin, and collagen types I and III will be expressed as fold-change values; fold change values will be calculated based on the double delta Ct method (where fold change = 2-∆∆CT).
Assessment of efficacy by performing Immunohistochemistry at day 27(after completion of Nefopam cream application).
时间窗: Two punch biopsies will be performed on the maximally thick region of each scar on Day 27 (after completion of Nefopam cream application).
To determine the efficacy of Nefopam cream versus placebo, protein expression of fibrotic molecules will be measured by immunohistochemistry. a-SMA (smooth muscle actin) and β -catenin immunohistochemistry will be performed at day 27.
Assessment of efficacy by measuring scar/wound depth at day 27.
时间窗: Dermal ultrasound analysis of the wound/scar will be performed at day 27.
To check the efficacy of the Nefopam cream all comparisons will be made between the Nefopam cream and the Placebo at different time point. At each visit there are three (3) measurements of wound depth at three (3) different points (deep end, mid-point, superficial end) will be taken. Scar depth will be measured in mm, based on ultrasound readings taken at scheduled assessment times.
Assessment of efficacy by measuring scar/wound depth at day 76.
时间窗: Dermal ultrasound analysis of the wound/scar will be performed at day 76.
To check the efficacy of the Nefopam cream all comparisons will be made between the Nefopam cream and the Placebo at different time point. At each visit there are three (3) measurements of wound depth at three (3) different points (deep end, mid-point, superficial end) will be taken. Scar depth will be measured in mm, based on ultrasound readings taken at scheduled assessment times.
Assessment of efficacy by measuring scar/wound depth at day 104.
时间窗: Dermal ultrasound analysis of the wound/scar will be performed at day 104.
To check the efficacy of the Nefopam cream all comparisons will be made between the Nefopam cream and the Placebo at different time point. At each visit there are three (3) measurements of wound depth at three (3) different points (deep end, mid-point, superficial end) will be taken. Scar depth will be measured in mm, based on ultrasound readings taken at scheduled assessment times.
Assessment of efficacy by measuring scar erythema and pigmentation at day 1.
时间窗: Mexameter® assessments of the wound/scar will be performed at day 1.
To check the efficacy of the Nefopam cream all comparisons will be made between the Nefopam cream and the Placebo at different time point. Once the wound has been determined to be closed, Mexameter® assessments will be performed at scheduled visits to check scar erythema and pigmentation . Mexameter® assessments will be performed at three standardized positions along each scar. At each position, three individual measurements will be taken and the mean and standard deviation will be determined for both erythema and pigmentation at each of the three measurement positions.
Assessment of efficacy by measuring scar erythema and pigmentation at day 21.
时间窗: Mexameter® assessments of the wound/scar will be performed at day 21.
To check the efficacy of the Nefopam cream all comparisons will be made between the Nefopam cream and the Placebo at different time point. Once the wound has been determined to be closed, Mexameter® assessments will be performed at scheduled visits to check scar erythema and pigmentation . Mexameter® assessments will be performed at three standardized positions along each scar. At each position, three individual measurements will be taken and the mean and standard deviation will be determined for both erythema and pigmentation at each of the three measurement positions.
Assessment of efficacy by measuring scar erythema and pigmentation at day 27.
时间窗: Mexameter® assessments of the wound/scar will be performed at day 27.
To check the efficacy of the Nefopam cream all comparisons will be made between the Nefopam cream and the Placebo at different time point. Once the wound has been determined to be closed, Mexameter® assessments will be performed at scheduled visits to check scar erythema and pigmentation . Mexameter® assessments will be performed at three standardized positions along each scar. At each position, three individual measurements will be taken and the mean and standard deviation will be determined for both erythema and pigmentation at each of the three measurement positions.
Assessment of efficacy by measuring scar erythema and pigmentation at day 48.
时间窗: Mexameter® assessments of the wound/scar will be performed at day 48.
To check the efficacy of the Nefopam cream all comparisons will be made between the Nefopam cream and the Placebo at different time point. Once the wound has been determined to be closed, Mexameter® assessments will be performed at scheduled visits to check scar erythema and pigmentation . Mexameter® assessments will be performed at three standardized positions along each scar. At each position, three individual measurements will be taken and the mean and standard deviation will be determined for both erythema and pigmentation at each of the three measurement positions.
Assessment of efficacy by measuring scar erythema and pigmentation at day 76.
时间窗: Mexameter® assessments of the wound/scar will be performed at day 76.
To check the efficacy of the Nefopam cream all comparisons will be made between the Nefopam cream and the Placebo at different time point. Once the wound has been determined to be closed, Mexameter® assessments will be performed at scheduled visits to check scar erythema and pigmentation . Mexameter® assessments will be performed at three standardized positions along each scar. At each position, three individual measurements will be taken and the mean and standard deviation will be determined for both erythema and pigmentation at each of the three measurement positions.
Assessment of efficacy by measuring scar erythema and pigmentation at day 104.
时间窗: Mexameter® assessments of the wound/scar will be performed at day 104.
To check the efficacy of the Nefopam cream all comparisons will be made between the Nefopam cream and the Placebo at different time point. Once the wound has been determined to be closed, Mexameter® assessments will be performed at scheduled visits to check scar erythema and pigmentation . Mexameter® assessments will be performed at three standardized positions along each scar. At each position, three individual measurements will be taken and the mean and standard deviation will be determined for both erythema and pigmentation at each of the three measurement positions.
Assessment of efficacy by assessing scar/wound healing at day 6 (during Nefopam cream treatment).
时间窗: Wound healing will be measured at day 6 (during Nefopam cream treatment).
Wound healing, defined as 100% epithelialization of the wound with no exudate. Percentage of wounds healed by visit by treatment will be summarized. The difference in proportions of healed wounds will be calculated within treatment group (active treatment against placebo within that group).
Assessment of efficacy by assessing scar/wound healing at day 13 (during Nefopam cream treatment).
时间窗: Wound healing will be measured at day 13 (during Nefopam cream treatment).
Wound healing, defined as 100% epithelialization of the wound with no exudate. Percentage of wounds healed by visit by treatment will be summarized. The difference in proportions of healed wounds will be calculated within treatment group (active treatment against placebo within that group).
Assessment of efficacy by assessing scar/wound healing at day 20 (during Nefopam cream treatment).
时间窗: Wound healing will be measured at day 20 (during Nefopam cream treatment).
Wound healing, defined as 100% epithelialization of the wound with no exudate. Percentage of wounds healed by visit by treatment will be summarized. The difference in proportions of healed wounds will be calculated within treatment group (active treatment against placebo within that group).
Assessment of efficacy by assessing scar/wound healing at day 27 (after completion of Nefopam cream application).
时间窗: Wound healing will be measured at day 27 (after completion of Nefopam cream application).
Wound healing, defined as 100% epithelialization of the wound with no exudate. Percentage of wounds healed by visit by treatment will be summarized. The difference in proportions of healed wounds will be calculated within treatment group (active treatment against placebo within that group).
Assessment of the scar using the Patient and Observer Scar Assessment Scales (POSAS) at day 27 (after completion of Nefopam cream application).
时间窗: Patient and Observer Scar Assessment Scales (POSAS) will be performed at day 27 (after completion of Nefopam cream application).
The POSAS consists of a section completed by the subject and sections completed by three observers - once for each hip, at each post-wound-closure visit. The Patient section consists of seven (7) questions on 10-point scales regarding scar pain, itchiness, colour, stiffness, thickness, irregularity, and an overall assessment. The Observer sections consist of seven (7) 10-point scales regarding vascularity, pigmentation, thickness, relief, pliability, surface area, and overall assessment. On Y axis POSAS scoring will be taken and on X axis outcome from the patients at different time point will be recorded. Each of the seven questions has a 10-point scoring system, with 1 representing normal skin and 10 the worst imaginable scar or sensation. The total score of both scales consists of adding the scores of each of the seven questions (range, 7 to 70). The lowest score, 7, reflects normal skin, whereas the highest score, 70, reflects the worst imaginable scar.
Assessment of efficacy by assessing scar/wound healing at day 48 (after completion of Nefopam cream application).
时间窗: Wound healing will be measured at day 48 (after completion of Nefopam cream application).
Wound healing, defined as 100% epithelialization of the wound with no exudate. Percentage of wounds healed by visit by treatment will be summarized. The difference in proportions of healed wounds will be calculated within treatment group (active treatment against placebo within that group).
Assessment of efficacy by measuring scar/wound area at day 1.
时间窗: Digital photography of the wound/scar will be performed at day 1.
To check the efficacy of the Nefopam cream all comparisons will be made between the Nefopam cream and the Placebo at different time point. Wound area will be measured using images obtained through digital photography on day 1 post operatively. Each image will be analyzed twice and the values averaged to provide an estimate of wound area (mm2) for each wound. Within-subject differences in wound area will be calculated and summarized by treatment group.
Assessment of efficacy by assessing scar/wound healing at day 104 (after completion of Nefopam cream application).
时间窗: Wound healing will be measured at day 104 (after completion of Nefopam cream application).
Wound healing, defined as 100% epithelialization of the wound with no exudate. Percentage of wounds healed by visit by treatment will be summarized. The difference in proportions of healed wounds will be calculated within treatment group (active treatment against placebo within that group).
Assessment of the scar using the Patient and Observer Scar Assessment Scales (POSAS) at day 104 (after completion of Nefopam cream application).
时间窗: Patient and Observer Scar Assessment Scales (POSAS) will be performed at day 104 (after completion of Nefopam cream application).
The POSAS consists of a section completed by the subject and sections completed by three observers - once for each hip, at each post-wound-closure visit. The Patient section consists of seven (7) questions on 10-point scales regarding scar pain, itchiness, colour, stiffness, thickness, irregularity, and an overall assessment. The Observer sections consist of seven (7) 10-point scales regarding vascularity, pigmentation, thickness, relief, pliability, surface area, and overall assessment. On Y axis POSAS scoring will be taken and on X axis outcome from the patients at different time point will be recorded. Each of the seven questions has a 10-point scoring system, with 1 representing normal skin and 10 the worst imaginable scar or sensation. The total score of both scales consists of adding the scores of each of the seven questions (range, 7 to 70). The lowest score, 7, reflects normal skin, whereas the highest score, 70, reflects the worst imaginable scar.
次要结局
- Assessment of Safety by assessing drug tolerability.(Treatment tolerability will be assessed regularly during the first 21 days of the trial.)
- Assessment of heart rate.(Hear rate will be measured at day 27, 76, and 104.)
- Assessment of temperature.(Body temperature will be measured at day 27, 76, and 104.)
- Assessment of blood pressure.(Blood pressure will be measured at day 27, 76, and 104.)
- Assessment of respiration.(Respiration will be measured at day 27, 76, and 104.)
- Measurement of routine hematology parameters.(Routine hematology parameters will be measured at day 27, 76 and 104.)
- Measurement of routine clinical chemistry parameters.(Routine clinical chemistry parameters will be measured at day 27, 76 and 104.)
- Serum Nefopam absorption assessment.(Serum Nefopam analysis will be carried out at time zero, 8 hours and 24 hours after initiation of the treament.)